Objective To investigate the prevalence and clinical significance of the centromere protein-F-like(CENP-F-like)immunofluorescence staining pattern in a large patient cohort and through literature review.Methods We ret...Objective To investigate the prevalence and clinical significance of the centromere protein-F-like(CENP-F-like)immunofluorescence staining pattern in a large patient cohort and through literature review.Methods We retrospectively analyzed antinuclear antibody(ANA)immunofluorescence assay results from 191274 patients at West China Hospital of Sichuan University between March 2018 and November 2020.Specific immunological markers were tested in sera with CENP-F-like patterns.Additionally,a narrative review of seven relevant studies was performed for comparison.Results In Southwest China,ANA positivity was found in 32.09%of patients,with the CENP-F-like pattern detected in 0.015%of all cases and 0.05%of ANA-positive individuals.The CENP-F-like pattern appeared predominantly at titers≥1∶320,most often in isolation(68.97%),but also mixed with cytoplasmic speckled patterns.Patients with cancers accounted for the highest proportion(31.03%),including solid tumors and hematologic malignancies.Metastasis was observed in patients with solid tumors,while graft-versus-host disease(GVHD)occurred in those with hematologic malignancies post-transplantation.Autoimmune diseases(AIDs)were diagnosed in 20.69%of cases,all showing disease-specific autoantibodies.These findings were broadly consistent with previous reports and suggest a possible association between the CENP-F-like pattern and malignancies.Conclusion The CENP-F-like pattern is rare in ANA tests but may be associated with clinically important conditions,particularly cancers and AIDs.The occurrence of metastasis and GVHD in patients with this pattern highlights its potential clinical relevance,and concurrent autoantibodies may assist in diagnosing AIDs.展开更多
Background and AimsAutoimmune hepatitis(AIH)frequently coexists with extrahepatic autoimmune diseases(EADs),but their prevalence,characteristics,progression,and treatment effect in the Han Chinese population remain un...Background and AimsAutoimmune hepatitis(AIH)frequently coexists with extrahepatic autoimmune diseases(EADs),but their prevalence,characteristics,progression,and treatment effect in the Han Chinese population remain unclear.This study aimed to evaluate the prevalence and spectrum of EADs and to assess their clinical features,disease course,and treatment outcomes in Han Chinese patients with AIH.MethodsMedical records of 371 Han Chinese patients with AIH(diagnosed from March 2016 to October 2023)were retrospectively analyzed.ResultsAmong the 371 AIH patients,304(81.94%)were female,with a median age of 52.5 years(interquartile range,46.0-61.0).A total of 23.98%(89/371)had at least one EAD,including 27.06%(82/303)in type 1 AIH,11.11%(7/63)in antibody-negative AIH,and none in type 2.A single EAD was the most common(20.21%,75/371).The most frequent EADs were Sjogren’s syndrome(8.63%)and autoimmune thyroid disease(8.36%).Compared with patients without EADs,those with EADs had lower alanine aminotransferase,red blood cell,and hemoglobin levels,but higher aspartate aminotransferase/alanine aminotransferase ratio and antinuclear antibody(ANA)positivity(all P<0.05).ANA positivity was independently associated with EADs(odds ratio=2.209,95%confidence interval=1.242-3.927,P=0.007).After three months of treatment,the complete biochemical response rate was lower in the EADs group than in the non-EADs group(40.0%vs.55.3%,P=0.024),whereas no significant differences were observed at 6,12,24,or 36 months(all P>0.05).ConclusionsIn the Han Chinese population,23.98%of AIH patients had EADs,with Sjogren’s syndrome and autoimmune thyroid disease being the most common.ANA positivity was a significant risk factor for EADs.EAD patients had a poorer initial treatment response at three months,but comparable long-term biochemical response from six months.展开更多
Background:In patients with autoimmune hemolytic anemia(AIHA),the risk of relapse is high owing to persistent autoreactive B-cell activity.Multirefractory AIHA is a more advanced stage of disease that is defined by a ...Background:In patients with autoimmune hemolytic anemia(AIHA),the risk of relapse is high owing to persistent autoreactive B-cell activity.Multirefractory AIHA is a more advanced stage of disease that is defined by a lack of response to at least three lines of therapy.CD19-directed chimeric antigen receptor(CAR)T-cell therapy results in profound B-cell depletion and may be a useful approach to achieving drug-free remission in multirefractory AIHA.展开更多
The rising incidence of dementia and associated neurodegenerative disorders poses a growing public health challenge.These conditions have traditionally been studied as isolated central nervous system disorders;however...The rising incidence of dementia and associated neurodegenerative disorders poses a growing public health challenge.These conditions have traditionally been studied as isolated central nervous system disorders;however,emerging evidence suggests that broader systemic factors,including chronic inflammation,immune dysregulation,metabolic dysfunction,and genetic susceptibility,may also play a role.This review ex-amines the interconnection between autoimmune diseases and metabolic syndromes in the pathogenesis and exacerbation of neurodegeneration.Conditions such as rheu-matoid arthritis,systemic lupus erythematosus,and type 1 diabetes mellitus have been associated with a heightened risk of developing dementia through chronic immune activation,blood-brain barrier disruption,and neuroinflammatory signaling.Similarly,metabolic disorders such as diabesity promote insulin resistance and oxidative stress,accelerating cognitive decline.The review also discusses glaucoma as a neurodegenera-tive condition with autoimmune features,underscoring the need for expanded classifi-cation and treatment strategies.A key focus is the utilization of the Collaborative Cross(CC)mouse model,which enables the study of gene-environment interactions across genetically diverse backgrounds.Findings from CC mice reveal strain-dependent sus-ceptibility to inflammation,cognitive impairment,and gut-brain axis dysfunction,pro-viding a translational bridge to human variability.This review highlights the importance of integrating precision-based approaches to dementia research that consider systemic influences.Advancing our understanding of these multiorgan interactions holds po-tential for designing precision-based therapeutic approaches to postpone the onset or reduce the incidence of neurodegenerative conditions.展开更多
AIM:To investigate the association between anti-DFS70 antibody positivity and ocular parameters,specifically,the choroidal vascularity index(CVI)and other optical coherence tomography(OCT)metrics,in a healthy populati...AIM:To investigate the association between anti-DFS70 antibody positivity and ocular parameters,specifically,the choroidal vascularity index(CVI)and other optical coherence tomography(OCT)metrics,in a healthy population.METHODS:This age-and sex-matched case-control study enrolled 84 healthy individuals with positive anti-DFS70 antibody findings and 84 healthy negative controls.All participants underwent detailed ophthalmological examinations,including biometry and OCT imaging.Anti-DFS70 positivity was determined by indirect immunofluorescence and scored semi-quantitatively(1+to 3+).CVI was calculated from OCT images using a standardized protocol with Image J software.Statistical analyses,including Student’s t-test,Mann-Whitney U test,Spearman correlation,and logistic regression,were used to compare groups and identify predictive factors.RESULTS:The individuals who tested positive and negative for anti-DFS70 included in the study were matched for age(median age=47y)and sex(F:M=7:1).CVI was significantly lower in the anti-DFS70-positive group compared to the negative group.A higher anti-DFS70 antibody titer was significantly associated with decreased subfoveal and nasal choroidal thickness(P=0.016 and P=0.014,respectively).In univariate regression analysis,CVI was the only significant predictor of anti-DFS70 positivity[odds ratio(OR)=0.02,P=0.025].Multivariate analysis revealed a positive correlation between macular thinning outside the subfoveal area and anti-DFS70 status(P<0.05).CONCLUSION:Our study demonstrates a novel association between anti-DFS70 antibody positivity and reduced choroidal vascularity in healthy individuals.These findings suggest that anti-DFS70 antibodies may be associated with subtle choroidal vascular changes detectable by OCT,even in asymptomatic individuals.Further longitudinal research is warranted to clarify the underlying mechanisms and long-term clinical significance of these ocular changes.展开更多
Loss of immune tolerance to central nervous system(CNS)antigens lies at the heart of multiple sclerosis(MS),the most common chronic autoimmune disease of the CNS.MS affects nearly2 million people wo rldwide and is cha...Loss of immune tolerance to central nervous system(CNS)antigens lies at the heart of multiple sclerosis(MS),the most common chronic autoimmune disease of the CNS.MS affects nearly2 million people wo rldwide and is chara cterized by focal areas of demyelination,inflammation,axonal injury,and neurodegeneration(Bronge et al.,2022;Magliozzi et al.,2023).展开更多
Small intestinal villi are essential for nutrient absorption,and their impairment can lead to malabsorption.Small intestinal villous atrophy(VA)encompasses a heterogeneous group of disorders,including immune-mediated ...Small intestinal villi are essential for nutrient absorption,and their impairment can lead to malabsorption.Small intestinal villous atrophy(VA)encompasses a heterogeneous group of disorders,including immune-mediated conditions(e.g.,celiac disease,autoimmune enteropathy,inborn errors of immunity),lymphoproliferative disorders(e.g.,enteropathy-associated T-cell lymphoma),infectious causes(e.g.,tropical sprue,Whipple’s disease),iatrogenic factors(e.g.,Olmesartanassociated enteropathy,graft-vs-host disease),as well as inflammatory and idiopathic types.These disorders are often rare and challenging to distinguish due to overlapping clinical,serological,endoscopic,and histopathological features.Through a systematic literature search using keywords such as small intestinal VA,malabsorption,and specific enteropathies,this review provides a comprehensive overview of diagnostic clues for VA and malabsorption.We systematically summarize the pathological characteristics of each condition to assist pathologists and clinicians in accurately identifying the underlying etiologies.Current studies still have many limitations and lack broader and deeper investigations into these diseases.Therefore,future research should focus on the development of novel diagnostic tools,predictive models,therapeutic targets,and mechanistic molecular studies to refine both diagnosis and management strategies.展开更多
Microglia cells are the resident innate immune cells of the central nervous system(CNS)(Paolicelli et al.,2022).They play a pivotal role in CNS development and in maintaining homeostasis during adulthood.Microglia are...Microglia cells are the resident innate immune cells of the central nervous system(CNS)(Paolicelli et al.,2022).They play a pivotal role in CNS development and in maintaining homeostasis during adulthood.Microglia are being extensively studied for their involvement in CNS disorders,ranging from autoimmune diseases such as multiple sclerosis to neurodegenerative and psychiatric conditions,as well as stroke and brain tumors(Paolicelli et al.,2022).展开更多
The interleukin-17 family is the key group of cytokines and displays a broad spectrum of biological functions,including regulating the inflammatory cascade in various autoimmune and inflammatory diseases,such as multi...The interleukin-17 family is the key group of cytokines and displays a broad spectrum of biological functions,including regulating the inflammatory cascade in various autoimmune and inflammatory diseases,such as multiple sclerosis,neuromyelitis optica spectrum disorder,myasthenia gravis,Guillain–Barre syndrome,acute disseminated encephalomyelitis,diabetes,inflammatory skin diseases,joint inflammation,and cancer.Although the function of the interleukin-17 family has attracted increasing research attention over many years,the expression,function,and regulation mechanisms of different interleukin-17 members are complicated and still only partially understood.Currently,the interleukin-17A pathway is considered a critical therapeutic target for numerous immune and chronic inflammatory diseases,with several monoclonal antibodies against interleukin-17A having been successfully used in clinical practice.Whether other interleukin-17 members have the potential to be targeted in other diseases is still debated.This review first summarizes the recent advancements in understanding the physicochemical properties,physiological functions,cellular origins,and downstream signaling pathways of different members and corresponding receptors of the interleukin-17 family.Subsequently,the function of interleukin-17 in various immune diseases is discussed,and the important role of interleukin-17 in the pathological process of immune diseases is demonstrated from multiple perspectives.Then,the current status of targeted interleukin-17 therapy is summarized,and the effectiveness and safety of targeted interleukin-17 therapy are analyzed.Finally,the clinical application prospects of targeting the interleukin-17 pathway are discussed.展开更多
Parkinson's disease is a neurodegenerative disorder marked by the degeneration of dopaminergic neurons and clinical symptoms such as tremors,rigidity,and slowed movements.A key feature of Parkinson's disease i...Parkinson's disease is a neurodegenerative disorder marked by the degeneration of dopaminergic neurons and clinical symptoms such as tremors,rigidity,and slowed movements.A key feature of Parkinson's disease is the accumulation of misfoldedα-synuclein,forming insoluble Lewy bodies in the substantia nigra pars compacta,which contributes to neurodegeneration.Theseα-synuclein aggregates may act as autoantigens,leading to T-cell-mediated neuroinflammation and contributing to dopaminergic cell death.Our perspective explores the hypothesis that Parkinson's disease may have an autoimmune component,highlighting research that connects peripheral immune responses with neurodegeneration.T cells derived from Parkinson's disease patients appear to have the potential to initiate an autoimmune response againstα-synuclein and its modified peptides,possibly leading to the formation of neo-epitopes.Recent evidence associates Parkinson's disease with abnormal immune responses,as indicated by increased levels of immune cells,such as CD4^(+)and CD8^(+)T cells,observed in both patients and mouse models.The convergence of T cells filtration increasing major histocompatibility complex molecules,and the susceptibility of dopaminergic neurons supports the hypothesis that Parkinson's disease may exhibit autoimmune characteristics.Understanding the immune mechanisms involved in Parkinson's disease will be crucial for developing therapeutic strategies that target the autoimmune aspects of the disease.Novel approaches,including precision medicine based on major histocompatibility complex/human leukocyte antigen typing and early biomarker identification,could pave the way for immune-based treatments aimed at slowing or halting disease progression.This perspective explores the relationship between autoimmunity and Parkinson's disease,suggesting that further research could deepen understanding and offer new therapeutic avenues.In this paper,it is organized to provide a comprehensive perspective on the autoimmune aspects of Parkinson's disease.It investigates critical areas such as the autoimmune response observed in Parkinson's disease patients and the role of autoimmune mechanisms targetingα-synuclein in Parkinson's disease.The paper also examines the impact of CD4~+T cells,specifically Th1 and Th17,on neurons through in vitro and ex vivo studies.Additionally,it explores howα-synuclein influences glia-induced neuroinflammation in Parkinson's disease.The discussion extends to the clinical implications and therapeutic landscape,offering insights into potential treatments.Consequently,we aim to provide a comprehensive perspective on the autoimmune aspects of Parkinson's disease,incorporating both supportive and opposing views on its classification as an autoimmune disorder and exploring implications for clinical applications.展开更多
OBJECTIVE:To elucidate the therapeutic efficacy and mechanism of action of Chaihu Guizhi Ganjiang decoction(柴胡桂枝干姜汤,CGGD)in autoimmune hepatitis.METHODS:CGGD components and potential target genes were extracted...OBJECTIVE:To elucidate the therapeutic efficacy and mechanism of action of Chaihu Guizhi Ganjiang decoction(柴胡桂枝干姜汤,CGGD)in autoimmune hepatitis.METHODS:CGGD components and potential target genes were extracted from previously published databases.The autoimmune hepatitis(AIH)-related regulatory genes were obtained from the Dis Ge NET database.Intersections were taken,and enrichment analyses were performed on the extracted data.Concanavalin A(Con A)-induced AIH model mice were treated with CGGD via gavage.The results of network pharmacological analysis were experimentally validated.RESULTS:Network pharmacology revealed 228 genes at the intersection of AIH and CGGD.Kyoto Encyclopedia of Genes and Genomes analysis revealed that CGGD primarily regulates the phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)signaling pathway and cellular metabolism in AIH.Gene Ontology enrichment analysis revealed that CGGD modulates inflammation through transcription factor-mediated signaling pathways.As predicted,CGGD attenuated Con A-induced AIH in a dose-dependent manner by activating the PI3K/AKT signaling pathway.Histopathological assessment confirmed the protective effects of CGGD against Con Ainduced AIH.Further investigation revealed that CGGD regulated the T helper cell 17(Th17)/regulatory T cell(Treg)balance by modulating the PI3K/Akt/nuclear factor kappa-B(NF-κB)pathway.CONCLUSIONS:This study demonstrated the therapeutic effect of CGGD on AIH through a combination of network pharmacological prediction and experimental validation.Its mechanism of action involves PI3K/Akt/NF-κB-mediated regulation of Th17/Treg cells.展开更多
Interferon regulatory factor 1 is involved in many autoimmune conditions and is increased in patients with myasthenia gravis.However,its function in myasthenia gravis remains unclear.Herein,we explored the function of...Interferon regulatory factor 1 is involved in many autoimmune conditions and is increased in patients with myasthenia gravis.However,its function in myasthenia gravis remains unclear.Herein,we explored the function of interferon regulatory factor 1 in myasthenia gravis,with an aim to understand the underlying mechanisms.Patients with myasthenia gravis who had acetylcholine receptor antibodies were included in the study.Peripheral blood lymphocytes were extracted from the included patients,and B lymphocyte subsets were isolated.Next,T and B cells from peripheral blood were co-cultured to explore the interferon regulatory factor 1-related mechanisms in myasthenia gravis.Chromatin immunoprecipitation experiments confirmed an interaction between interferon regulatory factor 1 and the CD180 promoter region.Dual-luciferase reporter gene confirmed the transcriptional activity of interferon regulatory factor 1 on CD180 promoter.In vitro results further indicated that interferon regulatory factor 1 promoted B cell activation and T cell differentiation via the inhibition of CD180.Interferon regulatory factor 1 recruited histone deacetylase 1 to inhibit CD180 transcription.Additionally,histone deacetylase 1 promoted B cell activation and T cell differentiation.Finally,in vitro experiments demonstrated that CD180 inhibited B cell activation and T cell differentiation by inhibiting the Toll-like receptor 4/mitogen-activated protein kinases/nuclear factor-kappa B pathway.Collectively,our results suggest that interferon regulatory factor 1 enhances T cell differentiation by recruiting histone deacetylase 1 to block B cell CD180 transcription in myasthenia gravis via the Toll-like receptor 4/mitogen-activated protein kinases/nuclear factor-kappa B pathway.Together,these findings indicate the important role of interferon regulatory factor 1 in myasthenia gravis and suggest its molecular mechanisms.They also provide new ideas and targets for diagnosing and treating myasthenia gravis,which will be both scientifically and clinically valuable.展开更多
Multiple sclerosis is a severe autoimmune disorder that is mainly mediated by pathogenic cluster of CD4^(+)T cell subsets.Despite advancements in the management of multiple sclerosis,there is a critical need for more ...Multiple sclerosis is a severe autoimmune disorder that is mainly mediated by pathogenic cluster of CD4^(+)T cell subsets.Despite advancements in the management of multiple sclerosis,there is a critical need for more effective and safer treatments.In the present study,we administered Lycium barbarum glycopeptide to a mouse model of experimental autoimmune encephalomyelitis-an animal model of multiple sclerosis-and evaluated its effects on pathogenic CD4^(+)T cell activation both in vivo and in vitro.Lycium barbarum glycopeptide significantly mitigated the clinical severity of experimental autoimmune encephalomyelitis,as demonstrated by reduced demyelination and neuroinflammation.Moreover,Lycium barbarum glycopeptide treatment decreased the infiltration of peripheral leukocytes into the central nervous system and suppressed pro-inflammatory cytokine expression.Lycium barbarum glycopeptide also modulated pathogenic CD4^(+)T cell activation by inhibiting T helper 1/T helper 17 cell differentiation while promoting regulatory T cell expansion.Notably,no side effects were observed,suggesting the long-term safety and tolerability of Lycium barbarum glycopeptide.Furthermore,RNA sequencing data indicated that Lycium barbarum glycopeptide inhibits activator protein-1,an essential regulator of T cell activation and differentiation.This finding was supported by the reversal of T helper/T helper 17 cell response suppression upon AP-1 blockade.Collectively,these results highlight the potential of Lycium barbarum glycopeptide as an innovative therapeutic agent for CD4^(+)T cell-associated autoimmune or inflammatory diseases,such as multiple sclerosis.展开更多
BACKGROUND Autoimmune hepatitis(AIH)is typically treated with immunomodulators and steroids.However,some patients are refractory to these treatments,necessitating alternative approaches.Biological therapies have recen...BACKGROUND Autoimmune hepatitis(AIH)is typically treated with immunomodulators and steroids.However,some patients are refractory to these treatments,necessitating alternative approaches.Biological therapies have recently been explored for these difficult cases.AIM To assess the efficacy and safety of biologics in AIH,focusing on patients unresponsive to standard treatments and evaluating outcomes such as serological markers and histological remission.METHODS A case-based systematic review was performed following the PRISMA protocol to evaluate the efficacy and safety of biological therapies in AIH.The primary focus was on serological improvement and histological remission.The secondary focus was on assessing therapy safety and additional outcomes.A standardized search command was applied to MEDLINE,EMBASE,and Cochrane Library databases to identify relevant studies.Inclusion criteria encompassed adult AIH patients treated with biologics.Data were analyzed based on demographics,prior treatments,and therapy-related outcomes.A narrative synthesis was employed to address biases and provide a comprehensive overview of the evidence.RESULTS A total of 352 studies were reviewed,with 30 selected for detailed analysis.Key findings revealed that Belimumab led to a favourable response in five out of eight AIH patients across two studies.Rituximab demonstrated high efficacy,with 41 out of 45 patients showing significant improvement across six studies.Basiliximab was assessed in a single study,where the sole patient treated experienced a beneficial outcome.Additionally,a notable number of AIH cases were induced by anti-tumor necrosis factor(TNF)medications,including 16 cases associated with infliximab and four cases with adalimumab.All these cases showed improvement upon withdrawal of the biologic agent.CONCLUSION Belimumab and Rituximab show promise as effective alternatives for managing refractory AIH,demonstrating significant improvements in clinical outcomes and liver function.However,the variability in patient responses to different therapies highlights the need for personalized treatment strategies.The risk of AIH induced by anti-TNF therapies underscores the need for vigilant monitoring and prompt symptom recognition.These findings support the incorporation of biologic agents into AIH treatment protocols,particularly for patients who do not respond to conventional therapies.展开更多
Chloroquine(CQ)and hydroxychloroquine(HCQ),originally developed as anti-malarial drugs,have found a new purpose in treating various autoimmune dis-eases due to their immunomodulatory properties.These drugs work throug...Chloroquine(CQ)and hydroxychloroquine(HCQ),originally developed as anti-malarial drugs,have found a new purpose in treating various autoimmune dis-eases due to their immunomodulatory properties.These drugs work through mu-ltiple mechanisms,including inhibiting Toll-like receptor signaling,suppressing antigen presentation,and modulating autophagy.This review article provides a comprehensive analysis of the immunomodulatory effects of CQ and HCQ in several autoimmune diseases such as systemic lupus erythematosus,rheumatoid arthritis,systemic sclerosis,and others.We delve into the intricate mechanisms of action,highlighting the key immune cells involved and discussing the clinical implications of these drugs in managing autoimmune conditions.Our review covers the latest research and clinical trials,offering a comprehensive under-standing of the therapeutic potential of CQ and HCQ in autoimmune diseases.We also discuss the challenges and controversies surrounding the use of these drugs,such as their long-term side effects and the need for personalized treatment approaches.By synthesizing current knowledge and identifying areas for future research,this review aims to provide a valuable resource for healthcare profes-sionals and researchers involved in the management of autoimmune diseases.展开更多
The human gut microbiota,a complex and diverse community of microorganisms,plays a crucial role in maintaining overall health by influencing various physio-logical processes,including digestion,immune function,and dis...The human gut microbiota,a complex and diverse community of microorganisms,plays a crucial role in maintaining overall health by influencing various physio-logical processes,including digestion,immune function,and disease susceptibi-lity.The balance between beneficial and harmful bacteria is essential for health,with dysbiosis-disruption of this balance-linked to numerous conditions such as metabolic disorders,autoimmune diseases,and cancers.This review highlights key genera such as Enterococcus,Ruminococcus,Bacteroides,Bifidobacterium,Escheri-chia coli,Akkermansia muciniphila,Firmicutes(including Clostridium and Lactoba-cillus),and Roseburia due to their well-established roles in immune regulation and metabolic processes,but other bacteria,including Clostridioides difficile,Salmonella,Helicobacter pylori,and Fusobacterium nucleatum,are also implicated in dysbiosis and various diseases.Pathogenic bacteria,including Escherichia coli and Bacteroides fragilis,contribute to inflammation and cancer progression by disrupting immune responses and damaging tissues.The potential for microbiota-based therapies,such as probiotics,prebiotics,fecal microbiota transplantation,and dietary inter-ventions,to improve health outcomes is examined.Future research directions in the integration of multi-omics,the impact of diet and lifestyle on microbiota com-position,and advancing microbiota engineering techniques are also discussed.Understanding the gut microbiota’s role in health and disease is essential for for-mulating personalized,efficacious treatments and preventive strategies,thereby enhancing health outcomes and progressing microbiome research.展开更多
Autoimmune enteropathy(AIE)is a rare immune mediated disorder primarily affecting children,characterized by chronic diarrhea,malabsorption,vomiting,weight loss and villous atrophy.It has also been observed in adults p...Autoimmune enteropathy(AIE)is a rare immune mediated disorder primarily affecting children,characterized by chronic diarrhea,malabsorption,vomiting,weight loss and villous atrophy.It has also been observed in adults presenting diagnostic and treatment challenges due to its overlap with other gastrointestinal disorders such as celiac disease.Initial diagnostic criteria for AIE include small bowel villous atrophy,lack of response to dietary restrictions,presence of anti-enterocyte antibodies,and predisposition to autoimmunity without severe immu-nodeficiency.Refined criteria emphasize characteristic histological findings and exclusion of other causes of villous atrophy.AIE is associated with various autoimmune disorders and can present with overlapping features with Celiac disease,including villous atrophy but without significant intraepithelial lympho-cytosis.Treatment primarily involves immunosuppression using corticosteroids,calcineurin inhibitors,and anti-tumor necrosis factor therapy,alongside nutri-tional support.Despite the challenges,understanding AIE’s diverse manifest-ations and improving diagnostic criteria are essential for effective management and improved patient outcome.Further research is needed to elucidate the pathogenesis,disease progression and long-term outcomes of AIE.展开更多
Background:Previous studies have highlighted the frequent occurrence of sarcopenia in patients with pancreatic diseases,including chronic pancreatitis.We aimed to clarify the prevalence of skeletal muscle(SM)loss and ...Background:Previous studies have highlighted the frequent occurrence of sarcopenia in patients with pancreatic diseases,including chronic pancreatitis.We aimed to clarify the prevalence of skeletal muscle(SM)loss and sarcopenia,and their associations with clinical characteristics,bone mineral density,and pancreatic imaging findings in patients with autoimmune pancreatitis(AIP).Methods:This study included 114 patients with AIP treated at Tohoku University Hospital.The SM index was assessed using a bioelectrical impedance analysis device,grip strength was measured using a hand dynamometer,and bone mineral density was evaluated using dual-energy X-ray absorptiometry.Univari-ate and multivariate logistic regression analyses were used to analyze factors associated with SM loss and sarcopenia.Results:Among 114 patients,57(50.0%)had SM loss,31(27.2%)had reduced grip strength,and 27(23.7%)had both.Patients with SM loss were older and had a lower body mass index,weaker grip strength,higher Controlling Nutritional Status scores,and lower serum lipase and albumin levels compared to those without SM loss.Computed tomography scans revealed a higher prevalence of pancreatic parenchy-mal atrophy in patients with SM loss.Similar differences were observed between patients with sarcopenia and those without.Osteopathy was observed in 35.6%of patients with SM loss and 38.1%of those with sarcopenia,whereas only 4.1%of patients without SM loss had osteopathy.Low BMI(<21.0 kg/m^(2))was also found to be an independent risk factor for SM loss in multivariate analysis.Age>72 years,low BMI(<20.0 kg/m^(2)),and low serum lipase levels(<13 U/L)were independent risk factors for sarcopenia in multivariate analysis.Conclusions:SM loss and sarcopenia are prevalent in patients with AIP and are associated with aging,poor nutritional status,low serum lipase levels,and pancreatic parenchymal atrophy.In addition to the high risk of osteopathy,careful attention should be paid to maintain muscle health in AIP patients.展开更多
BACKGROUND Hepatitis D virus-hepatitis B virus(HDV-HBV)co-infection accelerates liver disease progression and increases the risk of hepatocellular carcinoma,but the immunopathogenic mechanism of its combination with a...BACKGROUND Hepatitis D virus-hepatitis B virus(HDV-HBV)co-infection accelerates liver disease progression and increases the risk of hepatocellular carcinoma,but the immunopathogenic mechanism of its combination with autoimmune hepatitis(AIH)has not been clarified.This study reveals for the first time that HDV may induce AIH through abnormalities in immunoregulation in two specific cases.This is the first report of HDV-HBV co-infected patients who did not receive interferon therapy and achieved serological conversion and histological remission by combining antiviral(entecavir)with immunosuppression(prednisone+azathioprine)therapy,providing new evidence of the mechanism of this complex disease.CASE SUMMARY A 40-year-old female developed malaise and jaundice with an alanine aminotransferase/aspartate aminotransferase>20 upper limit of normal(ULN),total bilirubin:97.20μmol/L,immunoglobulin G(IgG)47.1 g/L(>3×ULN),HDV RNA 1.6×10^(7)copies/mL and liver biopsy showed G3S4.Tenofovir alafenamide combined with prednisone and azathioprine was administered,and three months later the Child-Turcotte-Pugh class C was reduced to class B and IgG decreased to 13.62 g/L.Another 58-year-old male complained of pain in the liver area,antinuclear antibody was 1:320,IgG 22.6 g/L(>1.3×ULN),and liver biopsy showed G2S3.Entecavir was administered in combination with prednisone and azathioprine,and after 3 months,liver function returned to normal,and IgG reduced to 14.22 g/L.CONCLUSION Patients with HDV-HBV co-infection combined with AIH can achieve clinical remission following combination therapy,and the study of immunomodulatory mechanisms should be emphasized.展开更多
Rheumatoid arthritis(RA)is an autoimmune disease characterized by inflammation and abnormal osteoclast activation,leading to bone destruction.We previously demonstrated that the large extracellular loop(LEL)of Tm4sf19...Rheumatoid arthritis(RA)is an autoimmune disease characterized by inflammation and abnormal osteoclast activation,leading to bone destruction.We previously demonstrated that the large extracellular loop(LEL)of Tm4sf19 is important for its function in osteoclast differentiation,and LEL-Fc,a competitive inhibitor of Tm4sf19,effectively suppresses osteoclast multinucleation and prevent bone loss associated with osteoporosis.This study aimed to investigate the role of Tm4sf19 in RA,an inflammatory and abnormal osteoclast disease,using a mouse model of collagen-induced arthritis(CIA).Tm4sf19 expression was observed in macrophages and osteoclasts within the inflamed synovium,and Tm4sf19 expression was increased together with inflammatory genes in the joint bones of CIA-induced mice compared with the sham control group.Inhibition of Tm4sf19 by LEL-Fc demonstrated both preventive and therapeutic effects in a CIA mouse model,reducing the CIA score,swelling,inflammation,cartilage damage,and bone damage.Knockout of Tm4sf19 gene or inhibition of Tm4sf19 activity by LEL-Fc suppressed LPS/IFN-γ-induced TLR4-mediated inflammatory signaling in macrophages.LEL-Fc disrupted not only the interaction between Tm4sf19 and TLR4/MD2,but also the interaction between TLR4 and MD2.μCT analysis showed that LEL-Fc treatment significantly reduced joint bone destruction and bone loss caused by hyperactivated osteoclasts in CIA mice.Taken together,these findings suggest that LELFc may be a potential treatment for RA and RA-induced osteoporosis by simultaneously targeting joint inflammation and bone destruction caused by abnormal osteoclast activation.展开更多
文摘Objective To investigate the prevalence and clinical significance of the centromere protein-F-like(CENP-F-like)immunofluorescence staining pattern in a large patient cohort and through literature review.Methods We retrospectively analyzed antinuclear antibody(ANA)immunofluorescence assay results from 191274 patients at West China Hospital of Sichuan University between March 2018 and November 2020.Specific immunological markers were tested in sera with CENP-F-like patterns.Additionally,a narrative review of seven relevant studies was performed for comparison.Results In Southwest China,ANA positivity was found in 32.09%of patients,with the CENP-F-like pattern detected in 0.015%of all cases and 0.05%of ANA-positive individuals.The CENP-F-like pattern appeared predominantly at titers≥1∶320,most often in isolation(68.97%),but also mixed with cytoplasmic speckled patterns.Patients with cancers accounted for the highest proportion(31.03%),including solid tumors and hematologic malignancies.Metastasis was observed in patients with solid tumors,while graft-versus-host disease(GVHD)occurred in those with hematologic malignancies post-transplantation.Autoimmune diseases(AIDs)were diagnosed in 20.69%of cases,all showing disease-specific autoantibodies.These findings were broadly consistent with previous reports and suggest a possible association between the CENP-F-like pattern and malignancies.Conclusion The CENP-F-like pattern is rare in ANA tests but may be associated with clinically important conditions,particularly cancers and AIDs.The occurrence of metastasis and GVHD in patients with this pattern highlights its potential clinical relevance,and concurrent autoantibodies may assist in diagnosing AIDs.
基金Jiangsu Province Traditional Chinese Medicine Science and Technology Development Program(YB2020037)Nanjing Infectious Disease Clinical Medical Center,Innovation Center for Infectious Disease of Jiangsu Province(NO.CXZX202232)Nanjing Health Science and Technology Development Special Fund Project(YKK22127).
文摘Background and AimsAutoimmune hepatitis(AIH)frequently coexists with extrahepatic autoimmune diseases(EADs),but their prevalence,characteristics,progression,and treatment effect in the Han Chinese population remain unclear.This study aimed to evaluate the prevalence and spectrum of EADs and to assess their clinical features,disease course,and treatment outcomes in Han Chinese patients with AIH.MethodsMedical records of 371 Han Chinese patients with AIH(diagnosed from March 2016 to October 2023)were retrospectively analyzed.ResultsAmong the 371 AIH patients,304(81.94%)were female,with a median age of 52.5 years(interquartile range,46.0-61.0).A total of 23.98%(89/371)had at least one EAD,including 27.06%(82/303)in type 1 AIH,11.11%(7/63)in antibody-negative AIH,and none in type 2.A single EAD was the most common(20.21%,75/371).The most frequent EADs were Sjogren’s syndrome(8.63%)and autoimmune thyroid disease(8.36%).Compared with patients without EADs,those with EADs had lower alanine aminotransferase,red blood cell,and hemoglobin levels,but higher aspartate aminotransferase/alanine aminotransferase ratio and antinuclear antibody(ANA)positivity(all P<0.05).ANA positivity was independently associated with EADs(odds ratio=2.209,95%confidence interval=1.242-3.927,P=0.007).After three months of treatment,the complete biochemical response rate was lower in the EADs group than in the non-EADs group(40.0%vs.55.3%,P=0.024),whereas no significant differences were observed at 6,12,24,or 36 months(all P>0.05).ConclusionsIn the Han Chinese population,23.98%of AIH patients had EADs,with Sjogren’s syndrome and autoimmune thyroid disease being the most common.ANA positivity was a significant risk factor for EADs.EAD patients had a poorer initial treatment response at three months,but comparable long-term biochemical response from six months.
文摘Background:In patients with autoimmune hemolytic anemia(AIHA),the risk of relapse is high owing to persistent autoreactive B-cell activity.Multirefractory AIHA is a more advanced stage of disease that is defined by a lack of response to at least three lines of therapy.CD19-directed chimeric antigen receptor(CAR)T-cell therapy results in profound B-cell depletion and may be a useful approach to achieving drug-free remission in multirefractory AIHA.
文摘The rising incidence of dementia and associated neurodegenerative disorders poses a growing public health challenge.These conditions have traditionally been studied as isolated central nervous system disorders;however,emerging evidence suggests that broader systemic factors,including chronic inflammation,immune dysregulation,metabolic dysfunction,and genetic susceptibility,may also play a role.This review ex-amines the interconnection between autoimmune diseases and metabolic syndromes in the pathogenesis and exacerbation of neurodegeneration.Conditions such as rheu-matoid arthritis,systemic lupus erythematosus,and type 1 diabetes mellitus have been associated with a heightened risk of developing dementia through chronic immune activation,blood-brain barrier disruption,and neuroinflammatory signaling.Similarly,metabolic disorders such as diabesity promote insulin resistance and oxidative stress,accelerating cognitive decline.The review also discusses glaucoma as a neurodegenera-tive condition with autoimmune features,underscoring the need for expanded classifi-cation and treatment strategies.A key focus is the utilization of the Collaborative Cross(CC)mouse model,which enables the study of gene-environment interactions across genetically diverse backgrounds.Findings from CC mice reveal strain-dependent sus-ceptibility to inflammation,cognitive impairment,and gut-brain axis dysfunction,pro-viding a translational bridge to human variability.This review highlights the importance of integrating precision-based approaches to dementia research that consider systemic influences.Advancing our understanding of these multiorgan interactions holds po-tential for designing precision-based therapeutic approaches to postpone the onset or reduce the incidence of neurodegenerative conditions.
文摘AIM:To investigate the association between anti-DFS70 antibody positivity and ocular parameters,specifically,the choroidal vascularity index(CVI)and other optical coherence tomography(OCT)metrics,in a healthy population.METHODS:This age-and sex-matched case-control study enrolled 84 healthy individuals with positive anti-DFS70 antibody findings and 84 healthy negative controls.All participants underwent detailed ophthalmological examinations,including biometry and OCT imaging.Anti-DFS70 positivity was determined by indirect immunofluorescence and scored semi-quantitatively(1+to 3+).CVI was calculated from OCT images using a standardized protocol with Image J software.Statistical analyses,including Student’s t-test,Mann-Whitney U test,Spearman correlation,and logistic regression,were used to compare groups and identify predictive factors.RESULTS:The individuals who tested positive and negative for anti-DFS70 included in the study were matched for age(median age=47y)and sex(F:M=7:1).CVI was significantly lower in the anti-DFS70-positive group compared to the negative group.A higher anti-DFS70 antibody titer was significantly associated with decreased subfoveal and nasal choroidal thickness(P=0.016 and P=0.014,respectively).In univariate regression analysis,CVI was the only significant predictor of anti-DFS70 positivity[odds ratio(OR)=0.02,P=0.025].Multivariate analysis revealed a positive correlation between macular thinning outside the subfoveal area and anti-DFS70 status(P<0.05).CONCLUSION:Our study demonstrates a novel association between anti-DFS70 antibody positivity and reduced choroidal vascularity in healthy individuals.These findings suggest that anti-DFS70 antibodies may be associated with subtle choroidal vascular changes detectable by OCT,even in asymptomatic individuals.Further longitudinal research is warranted to clarify the underlying mechanisms and long-term clinical significance of these ocular changes.
文摘Loss of immune tolerance to central nervous system(CNS)antigens lies at the heart of multiple sclerosis(MS),the most common chronic autoimmune disease of the CNS.MS affects nearly2 million people wo rldwide and is chara cterized by focal areas of demyelination,inflammation,axonal injury,and neurodegeneration(Bronge et al.,2022;Magliozzi et al.,2023).
基金Supported by National High-Level Hospital Clinical Research Funding,No.2022-PUMCH-B-022,and No.2022-PUMCH-D-002CAMS Innovation Fund for Medical Sciences,No.CIFMS 2021-1-I2M-003Undergraduate Innovation Program,No.2024dcxm025.
文摘Small intestinal villi are essential for nutrient absorption,and their impairment can lead to malabsorption.Small intestinal villous atrophy(VA)encompasses a heterogeneous group of disorders,including immune-mediated conditions(e.g.,celiac disease,autoimmune enteropathy,inborn errors of immunity),lymphoproliferative disorders(e.g.,enteropathy-associated T-cell lymphoma),infectious causes(e.g.,tropical sprue,Whipple’s disease),iatrogenic factors(e.g.,Olmesartanassociated enteropathy,graft-vs-host disease),as well as inflammatory and idiopathic types.These disorders are often rare and challenging to distinguish due to overlapping clinical,serological,endoscopic,and histopathological features.Through a systematic literature search using keywords such as small intestinal VA,malabsorption,and specific enteropathies,this review provides a comprehensive overview of diagnostic clues for VA and malabsorption.We systematically summarize the pathological characteristics of each condition to assist pathologists and clinicians in accurately identifying the underlying etiologies.Current studies still have many limitations and lack broader and deeper investigations into these diseases.Therefore,future research should focus on the development of novel diagnostic tools,predictive models,therapeutic targets,and mechanistic molecular studies to refine both diagnosis and management strategies.
文摘Microglia cells are the resident innate immune cells of the central nervous system(CNS)(Paolicelli et al.,2022).They play a pivotal role in CNS development and in maintaining homeostasis during adulthood.Microglia are being extensively studied for their involvement in CNS disorders,ranging from autoimmune diseases such as multiple sclerosis to neurodegenerative and psychiatric conditions,as well as stroke and brain tumors(Paolicelli et al.,2022).
基金supported by the National Natural Science Foundational of China(Key Program),No.U24A20692(to CJZ)the National Natural Science Foundational of China,Nos.82101414(to MLJ),82371355(to CJZ)+4 种基金the National Natural Science Foundational of China for Excellent Young Scholars,No.82022019(to CJZ)Sichuan Special Fund for Distinguished Young Scholars,No.24NSFJQ0052(to CJZ)The Innovation and Entrepreneurial Team of Sichuan Tianfu Emei Program,No.CZ2024018(to CJZ)Funding for Distinguished Young Scholars of Sichuan Provincial People’s Hospital,No.30420230005(to CJZ)Funding for Distinguished Young Scholars of University of Electronic Science and Technology of China,No.A1098531023601381(to CJZ)。
文摘The interleukin-17 family is the key group of cytokines and displays a broad spectrum of biological functions,including regulating the inflammatory cascade in various autoimmune and inflammatory diseases,such as multiple sclerosis,neuromyelitis optica spectrum disorder,myasthenia gravis,Guillain–Barre syndrome,acute disseminated encephalomyelitis,diabetes,inflammatory skin diseases,joint inflammation,and cancer.Although the function of the interleukin-17 family has attracted increasing research attention over many years,the expression,function,and regulation mechanisms of different interleukin-17 members are complicated and still only partially understood.Currently,the interleukin-17A pathway is considered a critical therapeutic target for numerous immune and chronic inflammatory diseases,with several monoclonal antibodies against interleukin-17A having been successfully used in clinical practice.Whether other interleukin-17 members have the potential to be targeted in other diseases is still debated.This review first summarizes the recent advancements in understanding the physicochemical properties,physiological functions,cellular origins,and downstream signaling pathways of different members and corresponding receptors of the interleukin-17 family.Subsequently,the function of interleukin-17 in various immune diseases is discussed,and the important role of interleukin-17 in the pathological process of immune diseases is demonstrated from multiple perspectives.Then,the current status of targeted interleukin-17 therapy is summarized,and the effectiveness and safety of targeted interleukin-17 therapy are analyzed.Finally,the clinical application prospects of targeting the interleukin-17 pathway are discussed.
基金supported by the National Research Foundation of South Korea(2023R1A2C2004516,RS-2023-00219399 to SPY,and 2022R1I1A1A01063513 to MGJ)。
文摘Parkinson's disease is a neurodegenerative disorder marked by the degeneration of dopaminergic neurons and clinical symptoms such as tremors,rigidity,and slowed movements.A key feature of Parkinson's disease is the accumulation of misfoldedα-synuclein,forming insoluble Lewy bodies in the substantia nigra pars compacta,which contributes to neurodegeneration.Theseα-synuclein aggregates may act as autoantigens,leading to T-cell-mediated neuroinflammation and contributing to dopaminergic cell death.Our perspective explores the hypothesis that Parkinson's disease may have an autoimmune component,highlighting research that connects peripheral immune responses with neurodegeneration.T cells derived from Parkinson's disease patients appear to have the potential to initiate an autoimmune response againstα-synuclein and its modified peptides,possibly leading to the formation of neo-epitopes.Recent evidence associates Parkinson's disease with abnormal immune responses,as indicated by increased levels of immune cells,such as CD4^(+)and CD8^(+)T cells,observed in both patients and mouse models.The convergence of T cells filtration increasing major histocompatibility complex molecules,and the susceptibility of dopaminergic neurons supports the hypothesis that Parkinson's disease may exhibit autoimmune characteristics.Understanding the immune mechanisms involved in Parkinson's disease will be crucial for developing therapeutic strategies that target the autoimmune aspects of the disease.Novel approaches,including precision medicine based on major histocompatibility complex/human leukocyte antigen typing and early biomarker identification,could pave the way for immune-based treatments aimed at slowing or halting disease progression.This perspective explores the relationship between autoimmunity and Parkinson's disease,suggesting that further research could deepen understanding and offer new therapeutic avenues.In this paper,it is organized to provide a comprehensive perspective on the autoimmune aspects of Parkinson's disease.It investigates critical areas such as the autoimmune response observed in Parkinson's disease patients and the role of autoimmune mechanisms targetingα-synuclein in Parkinson's disease.The paper also examines the impact of CD4~+T cells,specifically Th1 and Th17,on neurons through in vitro and ex vivo studies.Additionally,it explores howα-synuclein influences glia-induced neuroinflammation in Parkinson's disease.The discussion extends to the clinical implications and therapeutic landscape,offering insights into potential treatments.Consequently,we aim to provide a comprehensive perspective on the autoimmune aspects of Parkinson's disease,incorporating both supportive and opposing views on its classification as an autoimmune disorder and exploring implications for clinical applications.
基金Supported by the Nanjing Health Science and Technology Key Medical Science and Technology Development Program:Mechanism of Action of the Modified Si-Miao Powder with Sanguisorba Carbonisata in Regulating Microbiota and Microecology for the Treatment of Recurrent Vulvovaginal Candidiasis(ZKX22039)。
文摘OBJECTIVE:To elucidate the therapeutic efficacy and mechanism of action of Chaihu Guizhi Ganjiang decoction(柴胡桂枝干姜汤,CGGD)in autoimmune hepatitis.METHODS:CGGD components and potential target genes were extracted from previously published databases.The autoimmune hepatitis(AIH)-related regulatory genes were obtained from the Dis Ge NET database.Intersections were taken,and enrichment analyses were performed on the extracted data.Concanavalin A(Con A)-induced AIH model mice were treated with CGGD via gavage.The results of network pharmacological analysis were experimentally validated.RESULTS:Network pharmacology revealed 228 genes at the intersection of AIH and CGGD.Kyoto Encyclopedia of Genes and Genomes analysis revealed that CGGD primarily regulates the phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)signaling pathway and cellular metabolism in AIH.Gene Ontology enrichment analysis revealed that CGGD modulates inflammation through transcription factor-mediated signaling pathways.As predicted,CGGD attenuated Con A-induced AIH in a dose-dependent manner by activating the PI3K/AKT signaling pathway.Histopathological assessment confirmed the protective effects of CGGD against Con Ainduced AIH.Further investigation revealed that CGGD regulated the T helper cell 17(Th17)/regulatory T cell(Treg)balance by modulating the PI3K/Akt/nuclear factor kappa-B(NF-κB)pathway.CONCLUSIONS:This study demonstrated the therapeutic effect of CGGD on AIH through a combination of network pharmacological prediction and experimental validation.Its mechanism of action involves PI3K/Akt/NF-κB-mediated regulation of Th17/Treg cells.
基金National Natural Science Foundation of China,No.82271440Jiangxi Provincial Health Technology Project,No.202510009(both to LX).
文摘Interferon regulatory factor 1 is involved in many autoimmune conditions and is increased in patients with myasthenia gravis.However,its function in myasthenia gravis remains unclear.Herein,we explored the function of interferon regulatory factor 1 in myasthenia gravis,with an aim to understand the underlying mechanisms.Patients with myasthenia gravis who had acetylcholine receptor antibodies were included in the study.Peripheral blood lymphocytes were extracted from the included patients,and B lymphocyte subsets were isolated.Next,T and B cells from peripheral blood were co-cultured to explore the interferon regulatory factor 1-related mechanisms in myasthenia gravis.Chromatin immunoprecipitation experiments confirmed an interaction between interferon regulatory factor 1 and the CD180 promoter region.Dual-luciferase reporter gene confirmed the transcriptional activity of interferon regulatory factor 1 on CD180 promoter.In vitro results further indicated that interferon regulatory factor 1 promoted B cell activation and T cell differentiation via the inhibition of CD180.Interferon regulatory factor 1 recruited histone deacetylase 1 to inhibit CD180 transcription.Additionally,histone deacetylase 1 promoted B cell activation and T cell differentiation.Finally,in vitro experiments demonstrated that CD180 inhibited B cell activation and T cell differentiation by inhibiting the Toll-like receptor 4/mitogen-activated protein kinases/nuclear factor-kappa B pathway.Collectively,our results suggest that interferon regulatory factor 1 enhances T cell differentiation by recruiting histone deacetylase 1 to block B cell CD180 transcription in myasthenia gravis via the Toll-like receptor 4/mitogen-activated protein kinases/nuclear factor-kappa B pathway.Together,these findings indicate the important role of interferon regulatory factor 1 in myasthenia gravis and suggest its molecular mechanisms.They also provide new ideas and targets for diagnosing and treating myasthenia gravis,which will be both scientifically and clinically valuable.
基金supported by the National Natural Science Foundational of China,Nos.U24A20692(to CJZ),82371355(to CJZ),and 82101414(to MH)National NaturalScience Foundational of China for Excellent Young Scholars,No.82022019(to CJZ)+5 种基金Sichuan Special Fund for Distinguished Young Scholars,No.24NSFJQ0052(to CJZ)The Innovationand Entrepreneurial Team of Sichuan Tianfu Emei Program,No.CZ2024018(to CJZ)Funding for Distinguished Young Scholars of Sichuan Provincial People’sHospital,No.30420230005Funding for Distinguished Young Scholars of University of Electronic Science and Technology of China,No.A1098531023601381(toCJZ)Sichuan Science and Technology Support Project,No.2023YFS0212(to BH)Project of Sichuan Provincial Health Commission,No.19PJ265(to LD).
文摘Multiple sclerosis is a severe autoimmune disorder that is mainly mediated by pathogenic cluster of CD4^(+)T cell subsets.Despite advancements in the management of multiple sclerosis,there is a critical need for more effective and safer treatments.In the present study,we administered Lycium barbarum glycopeptide to a mouse model of experimental autoimmune encephalomyelitis-an animal model of multiple sclerosis-and evaluated its effects on pathogenic CD4^(+)T cell activation both in vivo and in vitro.Lycium barbarum glycopeptide significantly mitigated the clinical severity of experimental autoimmune encephalomyelitis,as demonstrated by reduced demyelination and neuroinflammation.Moreover,Lycium barbarum glycopeptide treatment decreased the infiltration of peripheral leukocytes into the central nervous system and suppressed pro-inflammatory cytokine expression.Lycium barbarum glycopeptide also modulated pathogenic CD4^(+)T cell activation by inhibiting T helper 1/T helper 17 cell differentiation while promoting regulatory T cell expansion.Notably,no side effects were observed,suggesting the long-term safety and tolerability of Lycium barbarum glycopeptide.Furthermore,RNA sequencing data indicated that Lycium barbarum glycopeptide inhibits activator protein-1,an essential regulator of T cell activation and differentiation.This finding was supported by the reversal of T helper/T helper 17 cell response suppression upon AP-1 blockade.Collectively,these results highlight the potential of Lycium barbarum glycopeptide as an innovative therapeutic agent for CD4^(+)T cell-associated autoimmune or inflammatory diseases,such as multiple sclerosis.
文摘BACKGROUND Autoimmune hepatitis(AIH)is typically treated with immunomodulators and steroids.However,some patients are refractory to these treatments,necessitating alternative approaches.Biological therapies have recently been explored for these difficult cases.AIM To assess the efficacy and safety of biologics in AIH,focusing on patients unresponsive to standard treatments and evaluating outcomes such as serological markers and histological remission.METHODS A case-based systematic review was performed following the PRISMA protocol to evaluate the efficacy and safety of biological therapies in AIH.The primary focus was on serological improvement and histological remission.The secondary focus was on assessing therapy safety and additional outcomes.A standardized search command was applied to MEDLINE,EMBASE,and Cochrane Library databases to identify relevant studies.Inclusion criteria encompassed adult AIH patients treated with biologics.Data were analyzed based on demographics,prior treatments,and therapy-related outcomes.A narrative synthesis was employed to address biases and provide a comprehensive overview of the evidence.RESULTS A total of 352 studies were reviewed,with 30 selected for detailed analysis.Key findings revealed that Belimumab led to a favourable response in five out of eight AIH patients across two studies.Rituximab demonstrated high efficacy,with 41 out of 45 patients showing significant improvement across six studies.Basiliximab was assessed in a single study,where the sole patient treated experienced a beneficial outcome.Additionally,a notable number of AIH cases were induced by anti-tumor necrosis factor(TNF)medications,including 16 cases associated with infliximab and four cases with adalimumab.All these cases showed improvement upon withdrawal of the biologic agent.CONCLUSION Belimumab and Rituximab show promise as effective alternatives for managing refractory AIH,demonstrating significant improvements in clinical outcomes and liver function.However,the variability in patient responses to different therapies highlights the need for personalized treatment strategies.The risk of AIH induced by anti-TNF therapies underscores the need for vigilant monitoring and prompt symptom recognition.These findings support the incorporation of biologic agents into AIH treatment protocols,particularly for patients who do not respond to conventional therapies.
基金Supported by the Oman Ministry of Higher Education,Research,and Innovation,No.BFP/RGP/HSS/24/015.
文摘Chloroquine(CQ)and hydroxychloroquine(HCQ),originally developed as anti-malarial drugs,have found a new purpose in treating various autoimmune dis-eases due to their immunomodulatory properties.These drugs work through mu-ltiple mechanisms,including inhibiting Toll-like receptor signaling,suppressing antigen presentation,and modulating autophagy.This review article provides a comprehensive analysis of the immunomodulatory effects of CQ and HCQ in several autoimmune diseases such as systemic lupus erythematosus,rheumatoid arthritis,systemic sclerosis,and others.We delve into the intricate mechanisms of action,highlighting the key immune cells involved and discussing the clinical implications of these drugs in managing autoimmune conditions.Our review covers the latest research and clinical trials,offering a comprehensive under-standing of the therapeutic potential of CQ and HCQ in autoimmune diseases.We also discuss the challenges and controversies surrounding the use of these drugs,such as their long-term side effects and the need for personalized treatment approaches.By synthesizing current knowledge and identifying areas for future research,this review aims to provide a valuable resource for healthcare profes-sionals and researchers involved in the management of autoimmune diseases.
文摘The human gut microbiota,a complex and diverse community of microorganisms,plays a crucial role in maintaining overall health by influencing various physio-logical processes,including digestion,immune function,and disease susceptibi-lity.The balance between beneficial and harmful bacteria is essential for health,with dysbiosis-disruption of this balance-linked to numerous conditions such as metabolic disorders,autoimmune diseases,and cancers.This review highlights key genera such as Enterococcus,Ruminococcus,Bacteroides,Bifidobacterium,Escheri-chia coli,Akkermansia muciniphila,Firmicutes(including Clostridium and Lactoba-cillus),and Roseburia due to their well-established roles in immune regulation and metabolic processes,but other bacteria,including Clostridioides difficile,Salmonella,Helicobacter pylori,and Fusobacterium nucleatum,are also implicated in dysbiosis and various diseases.Pathogenic bacteria,including Escherichia coli and Bacteroides fragilis,contribute to inflammation and cancer progression by disrupting immune responses and damaging tissues.The potential for microbiota-based therapies,such as probiotics,prebiotics,fecal microbiota transplantation,and dietary inter-ventions,to improve health outcomes is examined.Future research directions in the integration of multi-omics,the impact of diet and lifestyle on microbiota com-position,and advancing microbiota engineering techniques are also discussed.Understanding the gut microbiota’s role in health and disease is essential for for-mulating personalized,efficacious treatments and preventive strategies,thereby enhancing health outcomes and progressing microbiome research.
文摘Autoimmune enteropathy(AIE)is a rare immune mediated disorder primarily affecting children,characterized by chronic diarrhea,malabsorption,vomiting,weight loss and villous atrophy.It has also been observed in adults presenting diagnostic and treatment challenges due to its overlap with other gastrointestinal disorders such as celiac disease.Initial diagnostic criteria for AIE include small bowel villous atrophy,lack of response to dietary restrictions,presence of anti-enterocyte antibodies,and predisposition to autoimmunity without severe immu-nodeficiency.Refined criteria emphasize characteristic histological findings and exclusion of other causes of villous atrophy.AIE is associated with various autoimmune disorders and can present with overlapping features with Celiac disease,including villous atrophy but without significant intraepithelial lympho-cytosis.Treatment primarily involves immunosuppression using corticosteroids,calcineurin inhibitors,and anti-tumor necrosis factor therapy,alongside nutri-tional support.Despite the challenges,understanding AIE’s diverse manifest-ations and improving diagnostic criteria are essential for effective management and improved patient outcome.Further research is needed to elucidate the pathogenesis,disease progression and long-term outcomes of AIE.
基金supported in part by the Japan Pancreas Soci-ety and the MHLW Research Program on Rare and Intractable Dis-eases(Grant Number 23FC1015,Principal investigator:Mitsuhiro Kawano).
文摘Background:Previous studies have highlighted the frequent occurrence of sarcopenia in patients with pancreatic diseases,including chronic pancreatitis.We aimed to clarify the prevalence of skeletal muscle(SM)loss and sarcopenia,and their associations with clinical characteristics,bone mineral density,and pancreatic imaging findings in patients with autoimmune pancreatitis(AIP).Methods:This study included 114 patients with AIP treated at Tohoku University Hospital.The SM index was assessed using a bioelectrical impedance analysis device,grip strength was measured using a hand dynamometer,and bone mineral density was evaluated using dual-energy X-ray absorptiometry.Univari-ate and multivariate logistic regression analyses were used to analyze factors associated with SM loss and sarcopenia.Results:Among 114 patients,57(50.0%)had SM loss,31(27.2%)had reduced grip strength,and 27(23.7%)had both.Patients with SM loss were older and had a lower body mass index,weaker grip strength,higher Controlling Nutritional Status scores,and lower serum lipase and albumin levels compared to those without SM loss.Computed tomography scans revealed a higher prevalence of pancreatic parenchy-mal atrophy in patients with SM loss.Similar differences were observed between patients with sarcopenia and those without.Osteopathy was observed in 35.6%of patients with SM loss and 38.1%of those with sarcopenia,whereas only 4.1%of patients without SM loss had osteopathy.Low BMI(<21.0 kg/m^(2))was also found to be an independent risk factor for SM loss in multivariate analysis.Age>72 years,low BMI(<20.0 kg/m^(2)),and low serum lipase levels(<13 U/L)were independent risk factors for sarcopenia in multivariate analysis.Conclusions:SM loss and sarcopenia are prevalent in patients with AIP and are associated with aging,poor nutritional status,low serum lipase levels,and pancreatic parenchymal atrophy.In addition to the high risk of osteopathy,careful attention should be paid to maintain muscle health in AIP patients.
基金Supported by Xinjiang“Tianshan Talents”Medical and Health High-Level Talent Training Program-Young and Middle-Aged Backbone Medical Talents.
文摘BACKGROUND Hepatitis D virus-hepatitis B virus(HDV-HBV)co-infection accelerates liver disease progression and increases the risk of hepatocellular carcinoma,but the immunopathogenic mechanism of its combination with autoimmune hepatitis(AIH)has not been clarified.This study reveals for the first time that HDV may induce AIH through abnormalities in immunoregulation in two specific cases.This is the first report of HDV-HBV co-infected patients who did not receive interferon therapy and achieved serological conversion and histological remission by combining antiviral(entecavir)with immunosuppression(prednisone+azathioprine)therapy,providing new evidence of the mechanism of this complex disease.CASE SUMMARY A 40-year-old female developed malaise and jaundice with an alanine aminotransferase/aspartate aminotransferase>20 upper limit of normal(ULN),total bilirubin:97.20μmol/L,immunoglobulin G(IgG)47.1 g/L(>3×ULN),HDV RNA 1.6×10^(7)copies/mL and liver biopsy showed G3S4.Tenofovir alafenamide combined with prednisone and azathioprine was administered,and three months later the Child-Turcotte-Pugh class C was reduced to class B and IgG decreased to 13.62 g/L.Another 58-year-old male complained of pain in the liver area,antinuclear antibody was 1:320,IgG 22.6 g/L(>1.3×ULN),and liver biopsy showed G2S3.Entecavir was administered in combination with prednisone and azathioprine,and after 3 months,liver function returned to normal,and IgG reduced to 14.22 g/L.CONCLUSION Patients with HDV-HBV co-infection combined with AIH can achieve clinical remission following combination therapy,and the study of immunomodulatory mechanisms should be emphasized.
基金supported by GILO Foundation.This research is in part supported by Korea Drug Development Fund funded by Ministry of Science and ICT,Ministry of Trade,Industry,and Energy,and Ministry of Health and Welfare(RS-2023-00282595,Republic of Korea).
文摘Rheumatoid arthritis(RA)is an autoimmune disease characterized by inflammation and abnormal osteoclast activation,leading to bone destruction.We previously demonstrated that the large extracellular loop(LEL)of Tm4sf19 is important for its function in osteoclast differentiation,and LEL-Fc,a competitive inhibitor of Tm4sf19,effectively suppresses osteoclast multinucleation and prevent bone loss associated with osteoporosis.This study aimed to investigate the role of Tm4sf19 in RA,an inflammatory and abnormal osteoclast disease,using a mouse model of collagen-induced arthritis(CIA).Tm4sf19 expression was observed in macrophages and osteoclasts within the inflamed synovium,and Tm4sf19 expression was increased together with inflammatory genes in the joint bones of CIA-induced mice compared with the sham control group.Inhibition of Tm4sf19 by LEL-Fc demonstrated both preventive and therapeutic effects in a CIA mouse model,reducing the CIA score,swelling,inflammation,cartilage damage,and bone damage.Knockout of Tm4sf19 gene or inhibition of Tm4sf19 activity by LEL-Fc suppressed LPS/IFN-γ-induced TLR4-mediated inflammatory signaling in macrophages.LEL-Fc disrupted not only the interaction between Tm4sf19 and TLR4/MD2,but also the interaction between TLR4 and MD2.μCT analysis showed that LEL-Fc treatment significantly reduced joint bone destruction and bone loss caused by hyperactivated osteoclasts in CIA mice.Taken together,these findings suggest that LELFc may be a potential treatment for RA and RA-induced osteoporosis by simultaneously targeting joint inflammation and bone destruction caused by abnormal osteoclast activation.
