OBJECTIVE: To investigate the protective effects of Jiayan Kangtai(JYKT) granules, consisting of 9 Chinese herbs, in a rat model of autoimmune thyroiditis(AIT), and the possible underlying mechanism.METHODS: Female Le...OBJECTIVE: To investigate the protective effects of Jiayan Kangtai(JYKT) granules, consisting of 9 Chinese herbs, in a rat model of autoimmune thyroiditis(AIT), and the possible underlying mechanism.METHODS: Female Lewis rats(6-8 weeks) were randomly apportioned to 5 groups of 10, including a normal control. AIT was induced in the untreated AIT-model group, and rats treated subsequently with daily low, medium, or high dose JYKT granules. After 12 weeks, plasma levels of thyroid autoantibodies and morphological changes in the thyroid were detected by enzyme-linked immunosorbent assay and histological examination, respectively. The presence of interleukin(IL)-6,IL23 p19, and IL-2 in thyroid tissue was assessed by immunohistochemical staining. The percentages of T helper(Th)17 cells and regulatory T cells(Tregs) in the peripheral blood were analyzed by flow cytometry. Relevant levels of cytokines and proteins were examined via bead-based multiplex flow cytometry and ELISA, respectively. Expressions of genes and proteins regulated by Th17 cells and Tregs were shown by real-time PCR and Western blot.RESULTS: Compared to the control, AIT-model rats had higher plasma concentrations of thyroid autoantibodies. The high-dose JYKT rats showed significantly lower levels of thyroid autoantibodies compared with the AIT model group. Rats in the AIT-JYKT groups also had fewer thyroid lesions and less lymphocytic infiltration, a lower percentage of Th17 cells, and a higher percentage of Tregs, compared with the AIT-model. Rats given high-dose JYKT had a significantly lower Th17/Treg ratio compared with the AIT model. Differences in plasma cytokine concentrations and relevant gene and protein expressions in the spleens of JYKT-treated rats and the AIT group suggested an association between JYKT treatment and lower Th17 cell percentage and higher Treg activity.CONCLUSION: JYKT treatment appeared to be protective against AIT in rats, possibly via the regulation of the Th17 cell/Treg imbalance in AIT.展开更多
Vitamin D deficiency is a global problem,which has taken the form of a pandemic.Existing data indicate that vitamin D is not only a nutrient.It has also a hormone-specific activity.Vitamin D is characterized by anti-i...Vitamin D deficiency is a global problem,which has taken the form of a pandemic.Existing data indicate that vitamin D is not only a nutrient.It has also a hormone-specific activity.Vitamin D is characterized by anti-inflammatory and immunomodulatory properties.Chronic autoimmune thyroiditis is a disease of autoimmune genesis,in which lymphocytic infiltration gradually destroys thyroid tissue.There are some evidences about vitamin D deficiency and the development of chronic autoimmune thyroiditis.The article has reviewed the current literature about the impact and the benefits of vitamin D on thyroid antibodies levels.展开更多
Selenium （Se） is an essential trace element. Autoimmune thyroid diseases （AITD） are destructive inflammatory or anti-receptor autoimmune diseases characterized by reactivity to self-thyroid antigens. However, the ...Selenium （Se） is an essential trace element. Autoimmune thyroid diseases （AITD） are destructive inflammatory or anti-receptor autoimmune diseases characterized by reactivity to self-thyroid antigens. However, the effects of Se on the cytokines in AITD are still unclear. So we researched the role of Selenium （Se） and Thl/Th2 cytokine productions in the pathogenesis of autoimmune thyroid diseases （AITD）.展开更多
OBJECTIVE:To observe the effects of Buzhong Yiqi granule(补中益气颗粒)on thyroid function and ovarian function in rats with experimental autoimmune thyroiditis(EAT).METHODS:EAT model was replicate by using the method ...OBJECTIVE:To observe the effects of Buzhong Yiqi granule(补中益气颗粒)on thyroid function and ovarian function in rats with experimental autoimmune thyroiditis(EAT).METHODS:EAT model was replicate by using the method of mixing and injecting porcine thyroglobulin with Freund's adjuvant and high iodine.Rats were randomly divided into normal control(NC)group,EAT model(EAT)group,selenium yeast(PC)group,low dose Buzhong Yiqi(BZYQ-L)group,medium dose Buzhong Yiqi(BZYQ-M)group and high dose Buzhong Yiqi(BZYQ-H)group.After two months of drug intervention according to dosage,enzyme-linked immunosorbent assay(ELISA)was used to measure the levels of free triiodothyronine(FT3),free thyroxine(FT4),thyroid-stimulating hormone(TSH),antithyroid peroxidase antibody(TPOAb),thyroglobulin antibody(TGAb)in peripheral blood of rats.The pathological changes of rat thyroid tissues were observed under light microscope with HE staining;ELISA was used to determine estradiol(E2),follicle-stimulating hormone(FSH),luteinizing hormone(LH),testosterone(T),antimüllerian hormone(AMH),and the pathological changes of rat ovarian tissues were observed under light microscope with hematoxylin and eosin staining.RESULTS:Compared with the NC group,BZYQ granule improved the thyroid and ovarian tissue morphology,and the levels of TPOAb,TGAb and TSH in the model group rats significantly increased(P<0.05),the thyroid tissue was severely destroyed,the levels of E2,FSH,LH,T,AMH significantly increased(P<0.05),and the ovary exhibited polycystic changes;Compared with the model group,TSH level in the BZYQ-L group rats decreased(P<0.05),FSH,T,AMH levels decreased(P<0.05),in the BZYQ-M group TPOAb,TSH levels decreased(P<0.05),FSH,LH,T,AMH levels significantly decreased(P<0.05),BZYQ-H group TPOAb,TGAb,TSH levels significantly decreased(P<0.05),FSH,LH,T,AMH levels significantly decreased(P<0.05),with the greatest improvement and significantly better than selenium yeast group(P<0.05).CONCLUSIONS:BZYQ granule could regulate the thyroid function of EAT rats,reduce thyroid antibody titers,then act on the ovarian function,regulate hormone disorders,and alleviate the pathological damage of rat's ovarian tissues.The effect of high dose Buzhong Yiqi granule is the best.展开更多
OBJECTIVE:To observe the effect of herb-partitioned moxibustion(HPM)on the miRNA expression profile of thyroid tissue in experimental autoimmune thyroiditis(EAT)rats.METHODS:Rats were randomly divided into normal cont...OBJECTIVE:To observe the effect of herb-partitioned moxibustion(HPM)on the miRNA expression profile of thyroid tissue in experimental autoimmune thyroiditis(EAT)rats.METHODS:Rats were randomly divided into normal control(NC)group,EAT model(EAT)group,HPM group and western medicine(Med)group.EAT model rats were prepared by a combined immunization with complete and incomplete Freund’s adjuvant emulsified with porcine thyroglobulin and iodine.Rats in the HPM group were treated with HPM,while rats in the Med group were treated with levothyrocine(1μg/2 m L)by gavage.HE staining was used to observe the pathological morphological changes of thyroid tissue,ELISAs was uaed to detect the serum concentrations of TGAb,TPOAb,FT3,FT4,TSH.We then performed high-throughput mi RNA sequencing to analyse the mi RNA expression profiles in the thyroid tissues,followed by a bioinformatics analysis.RT-q PCR was used to verify the identified differentially expressed mi RNAs.RESULTS:HPM improved the thyroid tissue morphology and reduced serum TPOAb,TGAb,TSH concentration in EAT rats(P<0.05),but with no obvious effect on FT3 and FT4 concentration.While the TSH,FT3 and FT4 concentration was significantly changed in the Med group(P<0.01 or P<0.05)compared with that of EAT group.Sequencing results showed that a total of 17 mi RNAs were upregulated,and 4 were downregulated in the EAT rats,in which the expression levels of mi R-346 and mi R-331-5 p were reversed by HPM.The target genes of the mi RNAs that regulated by HPM wereassociated with a variety of immune factors and immune signals.RT-q PCR verification showed that the expression of mi RNA-346 and mi RNA-331-5 p was consistent with the sequencing results.CONCLUSIONS:HPM could regulate the the expression of mi RNA-346 and mi RNA-331-5 p,then act on their target genes to immune and inflammation-related pathways,which may be one of the mechanisms of HPM on EAT rats.展开更多
AIM:To investigate the prevalence of coeliac disease in a series of Turkish patients with autoimmune thyroiditis.METHODS:Sera from 136 consecutive patients with newly diagnosed autoimmune thyroiditis and 119 healthy b...AIM:To investigate the prevalence of coeliac disease in a series of Turkish patients with autoimmune thyroiditis.METHODS:Sera from 136 consecutive patients with newly diagnosed autoimmune thyroiditis and 119 healthy blood donors were tested for IgA tissue transglutaminase antibody with enzyme-linked immunosorbent assay.Endoscopic mucosal biopsy from the second part of duodenum was performed in patients with positive antibody test.RESULTS:Eight patients(5.9%)and one control subject(0.8%)were positive for IgA tissue transglutaminase antibody(OR:7.38,95% CI:0.91-59.85,P = 0.04).Six patients and one control agreed to take biopsies.Histopathological examination revealed changes classified as Marsh Ⅲa in one,Marsh Ⅱ in one,Marsh Ⅰ in two,and Marsh 0 in two patients with autoimmune throiditis,and MarshⅠin one blood donor.CONCLUSION:Turkish patients with autoimmune thyroiditis have an increased risk of coeliac disease and serological screening may be useful for early detection of coeliac disease in these patients.Our findings need to be confirmed in a larger series of patients.展开更多
A case report presents a progression of autoimmune thyroiditis with an abnormal enlargement of the thyroid glands and increased thyreotropin hormone concentration-associated with interferon treatment in human papillom...A case report presents a progression of autoimmune thyroiditis with an abnormal enlargement of the thyroid glands and increased thyreotropin hormone concentration-associated with interferon treatment in human papillomavirus infected patient with the autoimmune thyroiditis and a daily L-thyroxin hormone replacement therapy background. Observation was supplemented with a brief review of literature and discussion. On the basis of this observation and a brief review of literature authors suggested that the potential adverse effects of interferon therapy are overbalanced than its benefits for gynecological patients, therefore any interferon treatment should be recommended with strict indications as well as after screening of conditions and functions of thyroid glands and other interferon target organs to avoid interferon treatment side effects. Practitioners especially gynecologists should inform their patients about pleiotropic interferon effects and its high frequent and wide range side effects before to start such kind of treatment.展开更多
OBJECTIVE: To investigate the efficacy and potential mechanism of Bailing capsule( 百令胶囊, BL) antiautoimmune thyroiditis(AIT). METHODS: Based on the AIT rat model, the effect of BL in alleviating AIT was evaluated ...OBJECTIVE: To investigate the efficacy and potential mechanism of Bailing capsule( 百令胶囊, BL) antiautoimmune thyroiditis(AIT). METHODS: Based on the AIT rat model, the effect of BL in alleviating AIT was evaluated by detecting serum thyroid index free triiodothyronine(FT3), free thyroxine(FT4), thyroid-stimulating hormone(TSH), thyroglobulin antibody(TGAb), thyroid peroxidase antibody(TPOAb), and inflammatory factors Interferon-gamma(IFN-γ), Interleukin-4,-10, and-12(IL-4, IL-10, and IL-12) as well as thyroid tissue Hematoxylin-eosin(HE) staining and ultrastructure observation. The mechanism of BL was explored by combining transcriptome and proteome analysis, and further verified by Western blot(WB). RESULTS: BL effectively reduced serum FT3, FT4, TGAb, and TPOAb levels in AIT rats, restored TSH balance, inhibited the release of pro-inflammatory cytokines IFN-γ and IL-12, promoted the production of anti-inflammatory cytokines IL-4 and IL-10, and significantly reduced IFN-γ/IL-4 and IL-12/IL-10, improved thyroid follicular structure, and protected thyroid tissue from injury. Kyoto Encyclopedia of Genes and Genomes and protein interaction network analysis showed that BL affected the expression of fatty acidbinding protein 4, acyl-Co A synthetase long-chain family member 1, and acyl-Co A dehydrogenase long chain to regulate the peroxisome proliferator-activated receptor signaling pathway, thereby inhibiting the fatty acid metabolism and the inflammatory state of AIT rats.CONCLUSIONS: BL could effectively reduce thyroid inflammation in AIT model rats. The possible BL mechanism was to regulate the peroxisome proliferatoractivated receptor signaling pathway and inhibit fatty acid metabolism. This study suggested that BL has the potential to be used in clinical treatment of AIT.展开更多
Objective This study aimed to identify differentially methylated genes(DMGs) associated with natural killer cells in patients with autoimmune thyroiditis(AIT), focusing on the influence of varying water iodine exposur...Objective This study aimed to identify differentially methylated genes(DMGs) associated with natural killer cells in patients with autoimmune thyroiditis(AIT), focusing on the influence of varying water iodine exposure levels.Methods Participants were divided into categories based on median water iodine(MWI)concentrations: iodine-fortified areas(IFA, MWI < 10 μg/L), iodine-adequate areas(IAA, 40 ≤ MWI ≤ 100μg/L), and iodine-excessive areas(IEA, MWI > 300 μg/L). A total of 176 matched AIT cases and controls were recruited and divided into 89, 40, and 47 pairs for IFA, IAA, and IEA, respectively. DMGs were identified using 850K Bead Chip analysis for 10/10 paired samples. Validation of DNA methylation and m RNA expression levels of the DMGs was conducted using Methyl Target^(TM) and QRT-PCR for 176/176paired samples.Results KLRC1, KLRC3, and SH2D1B were identified as significant DMGs. Validation revealed that KLRC1 was hypomethylated and highly expressed, whereas KLRC3 was hypermethylated and highly expressed in individuals with AIT. Furthermore, KLRC1 was hypomethylated and highly expressed in both IFA and IEA.Conclusion The DNA methylation status of KLRC1 and KLRC3 may play crucial roles in AIT pathogenesis. Additionally, DNA methylation of KLRC1 seems to be influenced by different iodine concentrations in water.展开更多
Objective:To investigate the effect of Fuzheng Xiaoying Decoction on experimental autoimmune thyroiditis(EAT)model rats and explore its possible mechanism of immune regulation.Methods:Among the 40 female SD rats,10 we...Objective:To investigate the effect of Fuzheng Xiaoying Decoction on experimental autoimmune thyroiditis(EAT)model rats and explore its possible mechanism of immune regulation.Methods:Among the 40 female SD rats,10 were randomly selected as the blank group,and the rest were immunized with pig thyroglobulin and Freund's adjuvant combined with high iodine feeding to make the EAT model.After the model was established,they were randomly divided into three groups:the model group,the selenium yeast tablet group and the Fuzheng Xiaoying Decoction group,which were continuously gavaged for 2 months.The anti thyroid autoantibodies,thyroid function,IL-38 and Th17/Treg distribution were measured.The pathological changes of thyroid tissue were observed by HE staining.Results:Compared with the blank group,the levels of TPOAb and TGAb in the model group were significantly higher(P<0.05).Lymphocyte infiltration was seen in the thyroid tissue of the model group,and also the thyroid follicles were partially destroyed,the shape was irregular,and the colloid distribution was uneven,indicating that the modeling was successful.Compared with the model group,the levels of TPOAb and TGAb in the selenium yeast tablet group and the Fuzheng Xiaoying Decoction group decreased significantly(P<0.05).And the Fuzheng Xiaoying Decoction group had more significant improvement in thyroid follicle destruction and lymphocyte infiltration than the selenium yeast tablet group(P<0.05).Compared with the blank group,the levels of T3,T4,FT3 and FT4 in the model group increased,the level of IL-38 decreased,the proportion of Th17 increased,and the ratio of Th17/Treg increased(P<0.05).Compared with the model group,T4 level decreased,IL-38 level increased in the selenium yeast tablet group and the Fuzheng Xiaoying Decoction group(P<0.05).But there was no statistically significant difference in the reduction of Th17 proportion and Th17/Treg ratio between the above two groups and the model group(P>0.05).There was no significant difference in Treg ratio among the groups.Conclusion:Fuzheng Xiaoying Decoction can significantly reduce the level of anti thyroid autoantibodies in EAT rats by regulating the immunity of EAT rats,and improve the follicular destruction and lymphocyte infiltration of thyroid tissue in rats.展开更多
To explore im mune intervention effects of the combined use of cycloporin A (Cs A ) and 1,2 5 - dihydroxyvitam in D3[1,2 5 (OH ) 2 D3]at low doses on experimental autoim mune thyroiditis (EAT) ,porcine thyroglobulin...To explore im mune intervention effects of the combined use of cycloporin A (Cs A ) and 1,2 5 - dihydroxyvitam in D3[1,2 5 (OH ) 2 D3]at low doses on experimental autoim mune thyroiditis (EAT) ,porcine thyroglobulin (p TG) was injected into a CBA mouse at the dose of 10 0μg on day 0 and day14 to establish the model of EAT.The immune prevention group from day0 to day2 8, and treatm ent group from day10 to day38were daily adm inistered Cs A(10 mg/ kg) intragastri- cally and/ or1,2 5 (OH) 2 D3(0 .2 μg/ kg) ip.After im munized by p TG,the m ice were sacrificed on day2 8and day38to examine their thyroid gland pathologically,and to check the levels of serum porcine thyroglobulin antibodies (p TGAb) ,porcine thyromicrosom al antibodies (p TMAb) .The incidences of EAT in the immune prevention group and treatment group,with administration of low dose of Cs A and 1,2 5 (OH) 2 D3,were decreased respectively by 4 4 .4 4 % and 37.5 0 % .Those of severe disease in the two groups were decreased respectively by71.4 3% and6 0 .32 % .The levels of serum p TGAb and p TMAb in the imm une prevention group were lower than those of the positive control group.It was concluded thatcombined use of Cs A and1,2 5 (OH) 2 D3at low doses could effectively prevent EAT with a synergic effect.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
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
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 study the role of cadherin 1 (CDH1)gene DNA methylation in autoimmune thyroiditis (AIT)in population from different water-iodine regions.Methods From May to June 2019,the information of AIT cases and heal...Objective To study the role of cadherin 1 (CDH1)gene DNA methylation in autoimmune thyroiditis (AIT)in population from different water-iodine regions.Methods From May to June 2019,the information of AIT cases and healthy individuals in Shandong Province was collected in three types of water-iodine regions:iodinefortification (IF) region,iodine-adequate(IA) region and iodine-excess (IE) region.展开更多
Autoimmune hepatitis(AIH)is a rare cause of chronic liver disease.The exact pa-thophysiology of AIH is unknown.Breakdown of self-tolerance against hepatic antigens and molecular mimicry are often implicated in the pat...Autoimmune hepatitis(AIH)is a rare cause of chronic liver disease.The exact pa-thophysiology of AIH is unknown.Breakdown of self-tolerance against hepatic antigens and molecular mimicry are often implicated in the pathogenesis of AIH.Immunosuppressive therapy is the mainstay of treatment;however,10%–25%of patients with AIH may not respond to primary therapy.Those patients are often salvaged with second-and third-line immunosuppressive therapy.Workup for other concomitant diseases should be done for patients who fail to respond to primary immunosuppressive therapy.Concurrent metabolic dysfunction-asso-ciated steatotic liver disease,alcohol-related liver disease,overlap syndrome(AIH with primary biliary cholangitis or sclerosing cholangitis),chronic hepatitis B virus,hepatitis C virus,and human immunodeficiency virus infection should be ruled out in such cases.Targeting the concomitant etiology may lead to resolution of the clinical symptoms and induce biochemical and histological remission.Isolated AIH without other etiologies for liver injury should be managed with a higher dose of steroids,azathioprine,or other immunosuppressive agents.Second-and third-line immunosuppressive agents include mycophenolate mofetil,cyclosporine,tacrolimus,infliximab,and rituximab.Patients with AIH may present with acute severe AIH(AS-AIH)and AIH-related acute on chronic liver failure,and they often require liver transplantation.The terms refractory or difficult-to-treat AIH have been used interchangeably and have no distinct definition.Difficult-to-treat AIH includes patients with intolerable side effects,fulminant disease(AIH with acute on chronic liver failure and AS-AIH),AIH in pregnancy,and HIV infection.Patients who fail to respond to standard first-line immunosuppressive therapy should be classified as refractory AIH.This review addresses the issues in the management of difficult-to-treat AIH with recent advances in pharmacological management.展开更多
BACKGROUND Autoimmune autonomic ganglionopathy(AAG),formerly known as acute pandysautonomia,is a rare,acquired,antibody-mediated,potentially curable autonomic disorder that presents with diffuse autonomic failure.High...BACKGROUND Autoimmune autonomic ganglionopathy(AAG),formerly known as acute pandysautonomia,is a rare,acquired,antibody-mediated,potentially curable autonomic disorder that presents with diffuse autonomic failure.High levels of anti-ganglionic nicotinic acetylcholine receptor(gAChR)serum antibodies are detected in approximately 50%of AAG cases,confirming the diagnosis.CASE SUMMARY We present the case of a 68-year-old man who developed autonomic failure gradually over a 2-year period.Recently,the patient was unable to stand upright for more than a few seconds before fainting.Additionally,he presented with decreased sweating,dry mouth,urinary retention,early satiety,weight loss,bloating,constipation,and erectile dysfunction.Neurological examination revealed dilated pupils that were unresponsive to light.Deep tendon reflexes were absent or diminished.Serologic evaluation revealed the presence of gAChR autoantibodies.An orthostatic hypotension test yielded a positive result.The patient did not respond to symptomatic therapy,including midodrine,fludrocortisone and atomoxetine.Second-line therapy with immunoadsorption produced a noticeable clinical improvement;however,orthostatic hypotension persisted.Sequential rituximab infusion therapy successfully led to a significant improvement in symptoms.CONCLUSION Our case report supports the benefit of combined immunomodulatory therapy for refractory AAG cases that are unresponsive to single-agent treatment.展开更多
Recently,Jayabalan et al published an important study.The authors defined the liver outcome score as a novel biomarker for predicting liver-related mortality in patients with autoimmune hepatitis-primary biliary chola...Recently,Jayabalan et al published an important study.The authors defined the liver outcome score as a novel biomarker for predicting liver-related mortality in patients with autoimmune hepatitis-primary biliary cholangitis overlap syndrome.After thoroughly reviewing their work,we offer insights that primarily relate to their study design to enhance the medical community’s understanding of this complex disease.展开更多
Autoimmune liver disease overlap syndrome(OS)is a rare and clinically significant condition that has received limited attention in microbiome research.In their recent study,Wang et al combined 16S rRNA sequencing with...Autoimmune liver disease overlap syndrome(OS)is a rare and clinically significant condition that has received limited attention in microbiome research.In their recent study,Wang et al combined 16S rRNA sequencing with untargeted metabolomics to characterize the gut-liver axis in OS,identifying shared features of dysbiosis in autoimmune hepatitis(AIH)and primary biliary cholangitis(PBC),and unique signatures,including enrichment of Klebsiella and Escherichia and depletion of aromatic amino acids.In this letter,we critically appraise these findings,emphasizing that OS should be considered a distinct immunometabolic phenotype rather than a simple mixture of AIH and PBC.We discuss the potential mechanistic relevance of the Fusicatenibacter-tyrosine relationship,highlight the clinical implications of integrating microbiota-metabolite analyses,and outline the limitations that future studies must address.展开更多
基金Supported by the International Science and Technology Cooperation Project(No.2015DFA309010):Screening technology and formula optimization on traditional Chinese medicine intervention in Hashimoto's thyroiditis
文摘OBJECTIVE: To investigate the protective effects of Jiayan Kangtai(JYKT) granules, consisting of 9 Chinese herbs, in a rat model of autoimmune thyroiditis(AIT), and the possible underlying mechanism.METHODS: Female Lewis rats(6-8 weeks) were randomly apportioned to 5 groups of 10, including a normal control. AIT was induced in the untreated AIT-model group, and rats treated subsequently with daily low, medium, or high dose JYKT granules. After 12 weeks, plasma levels of thyroid autoantibodies and morphological changes in the thyroid were detected by enzyme-linked immunosorbent assay and histological examination, respectively. The presence of interleukin(IL)-6,IL23 p19, and IL-2 in thyroid tissue was assessed by immunohistochemical staining. The percentages of T helper(Th)17 cells and regulatory T cells(Tregs) in the peripheral blood were analyzed by flow cytometry. Relevant levels of cytokines and proteins were examined via bead-based multiplex flow cytometry and ELISA, respectively. Expressions of genes and proteins regulated by Th17 cells and Tregs were shown by real-time PCR and Western blot.RESULTS: Compared to the control, AIT-model rats had higher plasma concentrations of thyroid autoantibodies. The high-dose JYKT rats showed significantly lower levels of thyroid autoantibodies compared with the AIT model group. Rats in the AIT-JYKT groups also had fewer thyroid lesions and less lymphocytic infiltration, a lower percentage of Th17 cells, and a higher percentage of Tregs, compared with the AIT-model. Rats given high-dose JYKT had a significantly lower Th17/Treg ratio compared with the AIT model. Differences in plasma cytokine concentrations and relevant gene and protein expressions in the spleens of JYKT-treated rats and the AIT group suggested an association between JYKT treatment and lower Th17 cell percentage and higher Treg activity.CONCLUSION: JYKT treatment appeared to be protective against AIT in rats, possibly via the regulation of the Th17 cell/Treg imbalance in AIT.
文摘Vitamin D deficiency is a global problem,which has taken the form of a pandemic.Existing data indicate that vitamin D is not only a nutrient.It has also a hormone-specific activity.Vitamin D is characterized by anti-inflammatory and immunomodulatory properties.Chronic autoimmune thyroiditis is a disease of autoimmune genesis,in which lymphocytic infiltration gradually destroys thyroid tissue.There are some evidences about vitamin D deficiency and the development of chronic autoimmune thyroiditis.The article has reviewed the current literature about the impact and the benefits of vitamin D on thyroid antibodies levels.
基金supported by three programs from the National Natural Science Foundation of China (NSFC) (The experimental study on the effect of trace elements iodine and selenium on the autoimmune thyroid disease (No.30571564)The cross-sectional investigation on hypothyroidism induced by excess iodine intake and the experimental research on pathogenesy (No.30972465)The change of thyroid pathology and the levels of T3,T4 in SePP1,GPX3 knock out mice (No.30810103004)
文摘Selenium （Se） is an essential trace element. Autoimmune thyroid diseases （AITD） are destructive inflammatory or anti-receptor autoimmune diseases characterized by reactivity to self-thyroid antigens. However, the effects of Se on the cytokines in AITD are still unclear. So we researched the role of Selenium （Se） and Thl/Th2 cytokine productions in the pathogenesis of autoimmune thyroid diseases （AITD）.
基金National Natural Science Foundation of China:Action Mechanism of Buzhong Yiqi Decoction in Treating Hashimoto's Thyroiditis based on transforming growth factor β/Smad Signaling Pathway and the Balance between Treg and Th17 Cells(No.81973855)。
文摘OBJECTIVE:To observe the effects of Buzhong Yiqi granule(补中益气颗粒)on thyroid function and ovarian function in rats with experimental autoimmune thyroiditis(EAT).METHODS:EAT model was replicate by using the method of mixing and injecting porcine thyroglobulin with Freund's adjuvant and high iodine.Rats were randomly divided into normal control(NC)group,EAT model(EAT)group,selenium yeast(PC)group,low dose Buzhong Yiqi(BZYQ-L)group,medium dose Buzhong Yiqi(BZYQ-M)group and high dose Buzhong Yiqi(BZYQ-H)group.After two months of drug intervention according to dosage,enzyme-linked immunosorbent assay(ELISA)was used to measure the levels of free triiodothyronine(FT3),free thyroxine(FT4),thyroid-stimulating hormone(TSH),antithyroid peroxidase antibody(TPOAb),thyroglobulin antibody(TGAb)in peripheral blood of rats.The pathological changes of rat thyroid tissues were observed under light microscope with HE staining;ELISA was used to determine estradiol(E2),follicle-stimulating hormone(FSH),luteinizing hormone(LH),testosterone(T),antimüllerian hormone(AMH),and the pathological changes of rat ovarian tissues were observed under light microscope with hematoxylin and eosin staining.RESULTS:Compared with the NC group,BZYQ granule improved the thyroid and ovarian tissue morphology,and the levels of TPOAb,TGAb and TSH in the model group rats significantly increased(P<0.05),the thyroid tissue was severely destroyed,the levels of E2,FSH,LH,T,AMH significantly increased(P<0.05),and the ovary exhibited polycystic changes;Compared with the model group,TSH level in the BZYQ-L group rats decreased(P<0.05),FSH,T,AMH levels decreased(P<0.05),in the BZYQ-M group TPOAb,TSH levels decreased(P<0.05),FSH,LH,T,AMH levels significantly decreased(P<0.05),BZYQ-H group TPOAb,TGAb,TSH levels significantly decreased(P<0.05),FSH,LH,T,AMH levels significantly decreased(P<0.05),with the greatest improvement and significantly better than selenium yeast group(P<0.05).CONCLUSIONS:BZYQ granule could regulate the thyroid function of EAT rats,reduce thyroid antibody titers,then act on the ovarian function,regulate hormone disorders,and alleviate the pathological damage of rat's ovarian tissues.The effect of high dose Buzhong Yiqi granule is the best.
基金Supported by the National Natural Science Foundation of China(81704176,82074551)Three-year Action Plan Project of Shanghai Traditional Chinese Medicine Development(ZY(2018-2020)-CCCX-2004-01)+1 种基金the National Program on Key Basic Research Project(973 program)(2009CB522900,2015CB554501)Shanghai Municipal Health Commission Project(20194Y0013)。
文摘OBJECTIVE:To observe the effect of herb-partitioned moxibustion(HPM)on the miRNA expression profile of thyroid tissue in experimental autoimmune thyroiditis(EAT)rats.METHODS:Rats were randomly divided into normal control(NC)group,EAT model(EAT)group,HPM group and western medicine(Med)group.EAT model rats were prepared by a combined immunization with complete and incomplete Freund’s adjuvant emulsified with porcine thyroglobulin and iodine.Rats in the HPM group were treated with HPM,while rats in the Med group were treated with levothyrocine(1μg/2 m L)by gavage.HE staining was used to observe the pathological morphological changes of thyroid tissue,ELISAs was uaed to detect the serum concentrations of TGAb,TPOAb,FT3,FT4,TSH.We then performed high-throughput mi RNA sequencing to analyse the mi RNA expression profiles in the thyroid tissues,followed by a bioinformatics analysis.RT-q PCR was used to verify the identified differentially expressed mi RNAs.RESULTS:HPM improved the thyroid tissue morphology and reduced serum TPOAb,TGAb,TSH concentration in EAT rats(P<0.05),but with no obvious effect on FT3 and FT4 concentration.While the TSH,FT3 and FT4 concentration was significantly changed in the Med group(P<0.01 or P<0.05)compared with that of EAT group.Sequencing results showed that a total of 17 mi RNAs were upregulated,and 4 were downregulated in the EAT rats,in which the expression levels of mi R-346 and mi R-331-5 p were reversed by HPM.The target genes of the mi RNAs that regulated by HPM wereassociated with a variety of immune factors and immune signals.RT-q PCR verification showed that the expression of mi RNA-346 and mi RNA-331-5 p was consistent with the sequencing results.CONCLUSIONS:HPM could regulate the the expression of mi RNA-346 and mi RNA-331-5 p,then act on their target genes to immune and inflammation-related pathways,which may be one of the mechanisms of HPM on EAT rats.
文摘AIM:To investigate the prevalence of coeliac disease in a series of Turkish patients with autoimmune thyroiditis.METHODS:Sera from 136 consecutive patients with newly diagnosed autoimmune thyroiditis and 119 healthy blood donors were tested for IgA tissue transglutaminase antibody with enzyme-linked immunosorbent assay.Endoscopic mucosal biopsy from the second part of duodenum was performed in patients with positive antibody test.RESULTS:Eight patients(5.9%)and one control subject(0.8%)were positive for IgA tissue transglutaminase antibody(OR:7.38,95% CI:0.91-59.85,P = 0.04).Six patients and one control agreed to take biopsies.Histopathological examination revealed changes classified as Marsh Ⅲa in one,Marsh Ⅱ in one,Marsh Ⅰ in two,and Marsh 0 in two patients with autoimmune throiditis,and MarshⅠin one blood donor.CONCLUSION:Turkish patients with autoimmune thyroiditis have an increased risk of coeliac disease and serological screening may be useful for early detection of coeliac disease in these patients.Our findings need to be confirmed in a larger series of patients.
文摘A case report presents a progression of autoimmune thyroiditis with an abnormal enlargement of the thyroid glands and increased thyreotropin hormone concentration-associated with interferon treatment in human papillomavirus infected patient with the autoimmune thyroiditis and a daily L-thyroxin hormone replacement therapy background. Observation was supplemented with a brief review of literature and discussion. On the basis of this observation and a brief review of literature authors suggested that the potential adverse effects of interferon therapy are overbalanced than its benefits for gynecological patients, therefore any interferon treatment should be recommended with strict indications as well as after screening of conditions and functions of thyroid glands and other interferon target organs to avoid interferon treatment side effects. Practitioners especially gynecologists should inform their patients about pleiotropic interferon effects and its high frequent and wide range side effects before to start such kind of treatment.
基金Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine:Studies on the Antimalarial and Drug Resistance Mechanisms of Artemisinin and the Expansion of New Indications (No. ZYYCXTD-C-202002)。
文摘OBJECTIVE: To investigate the efficacy and potential mechanism of Bailing capsule( 百令胶囊, BL) antiautoimmune thyroiditis(AIT). METHODS: Based on the AIT rat model, the effect of BL in alleviating AIT was evaluated by detecting serum thyroid index free triiodothyronine(FT3), free thyroxine(FT4), thyroid-stimulating hormone(TSH), thyroglobulin antibody(TGAb), thyroid peroxidase antibody(TPOAb), and inflammatory factors Interferon-gamma(IFN-γ), Interleukin-4,-10, and-12(IL-4, IL-10, and IL-12) as well as thyroid tissue Hematoxylin-eosin(HE) staining and ultrastructure observation. The mechanism of BL was explored by combining transcriptome and proteome analysis, and further verified by Western blot(WB). RESULTS: BL effectively reduced serum FT3, FT4, TGAb, and TPOAb levels in AIT rats, restored TSH balance, inhibited the release of pro-inflammatory cytokines IFN-γ and IL-12, promoted the production of anti-inflammatory cytokines IL-4 and IL-10, and significantly reduced IFN-γ/IL-4 and IL-12/IL-10, improved thyroid follicular structure, and protected thyroid tissue from injury. Kyoto Encyclopedia of Genes and Genomes and protein interaction network analysis showed that BL affected the expression of fatty acidbinding protein 4, acyl-Co A synthetase long-chain family member 1, and acyl-Co A dehydrogenase long chain to regulate the peroxisome proliferator-activated receptor signaling pathway, thereby inhibiting the fatty acid metabolism and the inflammatory state of AIT rats.CONCLUSIONS: BL could effectively reduce thyroid inflammation in AIT model rats. The possible BL mechanism was to regulate the peroxisome proliferatoractivated receptor signaling pathway and inhibit fatty acid metabolism. This study suggested that BL has the potential to be used in clinical treatment of AIT.
基金supported by National Natural Science Foundation of China,82073490.
文摘Objective This study aimed to identify differentially methylated genes(DMGs) associated with natural killer cells in patients with autoimmune thyroiditis(AIT), focusing on the influence of varying water iodine exposure levels.Methods Participants were divided into categories based on median water iodine(MWI)concentrations: iodine-fortified areas(IFA, MWI < 10 μg/L), iodine-adequate areas(IAA, 40 ≤ MWI ≤ 100μg/L), and iodine-excessive areas(IEA, MWI > 300 μg/L). A total of 176 matched AIT cases and controls were recruited and divided into 89, 40, and 47 pairs for IFA, IAA, and IEA, respectively. DMGs were identified using 850K Bead Chip analysis for 10/10 paired samples. Validation of DNA methylation and m RNA expression levels of the DMGs was conducted using Methyl Target^(TM) and QRT-PCR for 176/176paired samples.Results KLRC1, KLRC3, and SH2D1B were identified as significant DMGs. Validation revealed that KLRC1 was hypomethylated and highly expressed, whereas KLRC3 was hypermethylated and highly expressed in individuals with AIT. Furthermore, KLRC1 was hypomethylated and highly expressed in both IFA and IEA.Conclusion The DNA methylation status of KLRC1 and KLRC3 may play crucial roles in AIT pathogenesis. Additionally, DNA methylation of KLRC1 seems to be influenced by different iodine concentrations in water.
基金supported by National Natural Science Foundation of China(No.81973855)。
文摘Objective:To investigate the effect of Fuzheng Xiaoying Decoction on experimental autoimmune thyroiditis(EAT)model rats and explore its possible mechanism of immune regulation.Methods:Among the 40 female SD rats,10 were randomly selected as the blank group,and the rest were immunized with pig thyroglobulin and Freund's adjuvant combined with high iodine feeding to make the EAT model.After the model was established,they were randomly divided into three groups:the model group,the selenium yeast tablet group and the Fuzheng Xiaoying Decoction group,which were continuously gavaged for 2 months.The anti thyroid autoantibodies,thyroid function,IL-38 and Th17/Treg distribution were measured.The pathological changes of thyroid tissue were observed by HE staining.Results:Compared with the blank group,the levels of TPOAb and TGAb in the model group were significantly higher(P<0.05).Lymphocyte infiltration was seen in the thyroid tissue of the model group,and also the thyroid follicles were partially destroyed,the shape was irregular,and the colloid distribution was uneven,indicating that the modeling was successful.Compared with the model group,the levels of TPOAb and TGAb in the selenium yeast tablet group and the Fuzheng Xiaoying Decoction group decreased significantly(P<0.05).And the Fuzheng Xiaoying Decoction group had more significant improvement in thyroid follicle destruction and lymphocyte infiltration than the selenium yeast tablet group(P<0.05).Compared with the blank group,the levels of T3,T4,FT3 and FT4 in the model group increased,the level of IL-38 decreased,the proportion of Th17 increased,and the ratio of Th17/Treg increased(P<0.05).Compared with the model group,T4 level decreased,IL-38 level increased in the selenium yeast tablet group and the Fuzheng Xiaoying Decoction group(P<0.05).But there was no statistically significant difference in the reduction of Th17 proportion and Th17/Treg ratio between the above two groups and the model group(P>0.05).There was no significant difference in Treg ratio among the groups.Conclusion:Fuzheng Xiaoying Decoction can significantly reduce the level of anti thyroid autoantibodies in EAT rats by regulating the immunity of EAT rats,and improve the follicular destruction and lymphocyte infiltration of thyroid tissue in rats.
文摘To explore im mune intervention effects of the combined use of cycloporin A (Cs A ) and 1,2 5 - dihydroxyvitam in D3[1,2 5 (OH ) 2 D3]at low doses on experimental autoim mune thyroiditis (EAT) ,porcine thyroglobulin (p TG) was injected into a CBA mouse at the dose of 10 0μg on day 0 and day14 to establish the model of EAT.The immune prevention group from day0 to day2 8, and treatm ent group from day10 to day38were daily adm inistered Cs A(10 mg/ kg) intragastri- cally and/ or1,2 5 (OH) 2 D3(0 .2 μg/ kg) ip.After im munized by p TG,the m ice were sacrificed on day2 8and day38to examine their thyroid gland pathologically,and to check the levels of serum porcine thyroglobulin antibodies (p TGAb) ,porcine thyromicrosom al antibodies (p TMAb) .The incidences of EAT in the immune prevention group and treatment group,with administration of low dose of Cs A and 1,2 5 (OH) 2 D3,were decreased respectively by 4 4 .4 4 % and 37.5 0 % .Those of severe disease in the two groups were decreased respectively by71.4 3% and6 0 .32 % .The levels of serum p TGAb and p TMAb in the imm une prevention group were lower than those of the positive control group.It was concluded thatcombined use of Cs A and1,2 5 (OH) 2 D3at low doses could effectively prevent EAT with a synergic effect.
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 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.
文摘Objective To study the role of cadherin 1 (CDH1)gene DNA methylation in autoimmune thyroiditis (AIT)in population from different water-iodine regions.Methods From May to June 2019,the information of AIT cases and healthy individuals in Shandong Province was collected in three types of water-iodine regions:iodinefortification (IF) region,iodine-adequate(IA) region and iodine-excess (IE) region.
文摘Autoimmune hepatitis(AIH)is a rare cause of chronic liver disease.The exact pa-thophysiology of AIH is unknown.Breakdown of self-tolerance against hepatic antigens and molecular mimicry are often implicated in the pathogenesis of AIH.Immunosuppressive therapy is the mainstay of treatment;however,10%–25%of patients with AIH may not respond to primary therapy.Those patients are often salvaged with second-and third-line immunosuppressive therapy.Workup for other concomitant diseases should be done for patients who fail to respond to primary immunosuppressive therapy.Concurrent metabolic dysfunction-asso-ciated steatotic liver disease,alcohol-related liver disease,overlap syndrome(AIH with primary biliary cholangitis or sclerosing cholangitis),chronic hepatitis B virus,hepatitis C virus,and human immunodeficiency virus infection should be ruled out in such cases.Targeting the concomitant etiology may lead to resolution of the clinical symptoms and induce biochemical and histological remission.Isolated AIH without other etiologies for liver injury should be managed with a higher dose of steroids,azathioprine,or other immunosuppressive agents.Second-and third-line immunosuppressive agents include mycophenolate mofetil,cyclosporine,tacrolimus,infliximab,and rituximab.Patients with AIH may present with acute severe AIH(AS-AIH)and AIH-related acute on chronic liver failure,and they often require liver transplantation.The terms refractory or difficult-to-treat AIH have been used interchangeably and have no distinct definition.Difficult-to-treat AIH includes patients with intolerable side effects,fulminant disease(AIH with acute on chronic liver failure and AS-AIH),AIH in pregnancy,and HIV infection.Patients who fail to respond to standard first-line immunosuppressive therapy should be classified as refractory AIH.This review addresses the issues in the management of difficult-to-treat AIH with recent advances in pharmacological management.
文摘BACKGROUND Autoimmune autonomic ganglionopathy(AAG),formerly known as acute pandysautonomia,is a rare,acquired,antibody-mediated,potentially curable autonomic disorder that presents with diffuse autonomic failure.High levels of anti-ganglionic nicotinic acetylcholine receptor(gAChR)serum antibodies are detected in approximately 50%of AAG cases,confirming the diagnosis.CASE SUMMARY We present the case of a 68-year-old man who developed autonomic failure gradually over a 2-year period.Recently,the patient was unable to stand upright for more than a few seconds before fainting.Additionally,he presented with decreased sweating,dry mouth,urinary retention,early satiety,weight loss,bloating,constipation,and erectile dysfunction.Neurological examination revealed dilated pupils that were unresponsive to light.Deep tendon reflexes were absent or diminished.Serologic evaluation revealed the presence of gAChR autoantibodies.An orthostatic hypotension test yielded a positive result.The patient did not respond to symptomatic therapy,including midodrine,fludrocortisone and atomoxetine.Second-line therapy with immunoadsorption produced a noticeable clinical improvement;however,orthostatic hypotension persisted.Sequential rituximab infusion therapy successfully led to a significant improvement in symptoms.CONCLUSION Our case report supports the benefit of combined immunomodulatory therapy for refractory AAG cases that are unresponsive to single-agent treatment.
基金Supported by The Key Research and Development Project of the Science and Technology Department of Sichuan Province,China,No.2023YFS0280The High-Level Research Initiation Fund of The First Affiliated Hospital of Chengdu Medical College,China,No.CYFY-GQ43.
文摘Recently,Jayabalan et al published an important study.The authors defined the liver outcome score as a novel biomarker for predicting liver-related mortality in patients with autoimmune hepatitis-primary biliary cholangitis overlap syndrome.After thoroughly reviewing their work,we offer insights that primarily relate to their study design to enhance the medical community’s understanding of this complex disease.
基金Supported by the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education,No.RS-2023-00237287.
文摘Autoimmune liver disease overlap syndrome(OS)is a rare and clinically significant condition that has received limited attention in microbiome research.In their recent study,Wang et al combined 16S rRNA sequencing with untargeted metabolomics to characterize the gut-liver axis in OS,identifying shared features of dysbiosis in autoimmune hepatitis(AIH)and primary biliary cholangitis(PBC),and unique signatures,including enrichment of Klebsiella and Escherichia and depletion of aromatic amino acids.In this letter,we critically appraise these findings,emphasizing that OS should be considered a distinct immunometabolic phenotype rather than a simple mixture of AIH and PBC.We discuss the potential mechanistic relevance of the Fusicatenibacter-tyrosine relationship,highlight the clinical implications of integrating microbiota-metabolite analyses,and outline the limitations that future studies must address.
