BACKGROUND Although breast milk is ideal for newborns,in some cases,it is replaced with cow’s milk,which contains proteins that increase the risk of cow’s milk protein allergy(CMPA).AIM To evaluate CMPA prevalence i...BACKGROUND Although breast milk is ideal for newborns,in some cases,it is replaced with cow’s milk,which contains proteins that increase the risk of cow’s milk protein allergy(CMPA).AIM To evaluate CMPA prevalence in Bahrain and compare clinical characteristics of children with immunoglobulin E(IgE)-and non-IgE-mediated CMPA.METHODS This retrospective cohort study examined children with CMPA diagnosed at the pediatric gastroenterology outpatient clinic of the Salmaniya Medical Complex,Bahrain,between 2014 and 2022,and assessed CMPA prevalence.Clinical presentations,laboratory findings,dietary modifications,and outcomes were compared between children with IgE-mediated and non-IgE-mediated CMPA.Categorical variables were compared using Fisher’s exact test or Pearson’sχ2 test,whereas continuous variables were compared using Student’s t-test or the Mann-Whitney U test.RESULTS Of 8332 patients,6022(72.3%)adhered to their appointment.Of them,618(10.3%)were suggested of having CMPA and 595(96.3%)were included;CMPA prevalence was 2%.Most patients were Bahraini(93.8%)and males(55.3%).Non-IgE-mediated type accounted for 77.3%cases and IgE-mediated type,22.7%.IgE-mediated CMPA presented more in boys(P=0.030),and later in life(5.1 months±4.5 months vs 4.2 months±4.2 months,P=0.016,95%CI:0.08-1.73),had more associated diseases(P<0.001);and presented with more cutaneous(P=0.024)and respiratory(P=0.003)manifestations,severe symptoms[rash/dry skin(P=0.031),facial swelling/angioedema(P=0.003),failure to thrive(P=0.013),apparent life-threatening event(P<0.001)],and positive physical findings(P=0.002)than non-IgE-mediated CMPA.Most patients were exclusively fed cow milk formula(50.3%).The amino acid-based formula(AAF)was most prescribed(60.5%)with no difference between the two types(P=0.173).Although breastfeeding was recommended to 49.6%,only 8.2%were exclusively breastfed.IgE-mediated CMPA was associated with a longer follow-up duration than non-IgE-mediated CMPA(17.3 months±14.0 months vs 13.5 months±13.4 months,P=0.005,95%CI:1.1-6.3).CONCLUSION This study revealed a high CMPA prevalence with clinical differences between both types that can influence treatment.AAF was most prescribed,while breastfeeding with dietary modification is rarely applied.展开更多
BACKGROUND Coronavirus disease 2019(COVID-19)pneumonia with severe septic shock and acute respiratory distress syndrome(ARDS)are critical illnesses for patients following transplant.Intravenous immunoglobulin(IVIG)pla...BACKGROUND Coronavirus disease 2019(COVID-19)pneumonia with severe septic shock and acute respiratory distress syndrome(ARDS)are critical illnesses for patients following transplant.Intravenous immunoglobulin(IVIG)plays a role in both immune support and inflammation control,especially in immunocompromised patients.This case report describes the first successful experience using IVIG and pulse steroids to manage this critical condition following lung transplantation.CASE SUMMARY A 65-year-old male patient reported a history of chronic obstructive pulmonary disease and poor lung function and received bilateral sequential lung transplantations.Postoperatively,he developed COVID-19 pneumonia,severe septic shock,and ARDS.He recovered from this critical condition after empirical antibiotics administration and veno-venous extracorporeal membrane oxygenation,in addition to IVIG and pulse steroids.CONCLUSION IVIG is a valuable adjunct in managing severe sepsis in lung transplant recipients after COVID-19 infection.We aim,for the first time,to report the success of such a management approach for COVID-19 ARDS and sepsis in the post-lung transplant setting.With further investigations,this is a starting point for wider analysis of such an approach in this setting and consequently helps guide clinical practice for such a challenging patient population moving forward.展开更多
Background The objective was to characterize the colostrum proteome of primiparous Holstein cows in association with immunoglobulin G(IgG)content.Immediately after calving,colostrum samples were collected from 18 cows...Background The objective was to characterize the colostrum proteome of primiparous Holstein cows in association with immunoglobulin G(IgG)content.Immediately after calving,colostrum samples were collected from 18 cows to measure IgG concentration.Based on colostrum IgG content,samples were classified through cluster analysis and were identified as poor,average,and excellent quality.The proteome was assessed with quantitative shotgun proteomics;abundance data were compared among the colostrum types;enrichment analysis of metabolic processes and proteins classes was performed as well.We also tested correlations between this proteome and blood globulin level of cows and passive immunity level of calves.Results On average,428 proteins were identified per sample,which belonged mainly to cellular process,biological regulation,response to stimulus,metabolic process,and immune system process.Most abundant proteins were complement C3(Q2UVX4),alpha-S1-casein(P02662),Ig-like domain-containing protein(A0A3Q1M032),albumin(A0A140T897),polymeric immunoglobulin receptor(P81265),lactotransferrrin(P24627),and IGHG1*01(X167014).Colostrum of excellent quality had greater(P<0.05)abundance of serpin A3-7(A2I7N3),complement factorl(A0A3Q1 MIF4),lipocalin/cytosolic fatty-acid binding domain-containing protein(A0A3Q1 MRQ2),complement C3(E1B805),complement component 4 binding protein alpha(A0AAF6ZHP5),and complement component C6(F1MM86).However,colostrum of excellent quality had lower(P<0.05)abundance of HGF activator(E1BCW0),alpha-S1-casein(P02662),and xanthine dehydrogenase/oxidase(P80457).This resulted in enrichment of the biological processes predominantly for complement activation alternative pathway,complement activation,complement activation classical pathway,humoral immune response,leukocyte mediated immunity,and negative regulation of endopeptidase activity in excellent-quality colostrum.Additionally,some colostrum proteins were found to be correlated with the blood globulin level of cows and with the passive immunity level of calves(P<0.05;r≥0.57).Conclusions This study provides new insights into the bovine colostrum proteome,demonstrating associations between IgG levels and the abundance of other proteins,as well as the enrichment of metabolic processes related to innate immune response.Thus,results suggest that the colostrum proteomic profile is associated with the content of IgG.Future research should deeply explore the association of these findings with pre-calving nutrition status and blood composition of the cow,and with passive immunity transfer to the calf.展开更多
Understanding the liquid-liquid phase separation(LLPS)of immunoglobulin G(IgG)is crucial,as it profoundly influences IgG’s biological activity and stability.In this study,we employed coarse-grained molecular dynamics...Understanding the liquid-liquid phase separation(LLPS)of immunoglobulin G(IgG)is crucial,as it profoundly influences IgG’s biological activity and stability.In this study,we employed coarse-grained molecular dynamics simulations to systematically investigate the phase separation behavior of IgG.We first constructed two types of IgG models:all-pair IgG model and partial-pair IgG model,and compared the coexistence curve from our simulations with experimental data.Our results showed that the partial-pair IgG model aligns better with the experimental critical temperature and critical density.Using this model,we then calculated the temperature-dependent variations of IgG’s radius of gyration,surface tension,viscosity,etc.More importantly,we demonstrated that variations in the interaction strengths among IgG molecules significantly influence their phase separation behavior.Specifically,a higher standard deviation of interaction strength at different temperatures is found to lead to more stable phase-separated states.Furthermore,we observed that the introduction of repulsive polymers and strongly attractive polymers consistently enhances IgG phase separation,while weakly attractive polymers exhibit a dual regulatory effect on the phase separation.Overall,this study provides valuable insights into the mechanisms governing IgG phase behavior,with potential implications for optimizing biopharmaceutical products.展开更多
Immunoglobulin(Ig)A nephropathy is the most common type of primary glomerulonephritis globally.It typically manifests with microscopic hematuria and a spectrum of proteinuria,although rapidly progressive glomeruloneph...Immunoglobulin(Ig)A nephropathy is the most common type of primary glomerulonephritis globally.It typically manifests with microscopic hematuria and a spectrum of proteinuria,although rapidly progressive glomerulonephritis may occur in rare instances.Deposition of IgA in the mesangium seems to be the underlying disease mechanism.Despite current treatment,IgA nephropathy may progress into end-stage renal disease,indicating the necessity for the development of new therapeutic agents.Lifestyle modifications and anti-proteinuric treatment are recommended,and steroids have shown to be beneficial to high risk groups.Nevertheless,other conventional immunosuppressive agents,such as cyclophosphamide and mycophenolate mofetil,may be considered,despite the lack of sufficient evidence to support their efficacy.A considerable proportion of cases remain unresponsive to these treatments,underscoring the need for novel therapeutic approaches.There are several promising immunosuppressive drugs,such as B-cell lineage depleting agents or complement system inhibitors,that are currently undergoing clinical trials.These therapies may be considered for use in selected cases.展开更多
Metal may affect maternal immune function,but few epidemiological studies have reported the associations between multiple-metal exposure and maternal immunoglobulin(Ig)levels.Based on the Hangzhou Birth Cohort Study,1...Metal may affect maternal immune function,but few epidemiological studies have reported the associations between multiple-metal exposure and maternal immunoglobulin(Ig)levels.Based on the Hangzhou Birth Cohort Study,1059 participants were included,and eleven metals in whole blood samples and serum IgA,IgG,IgE and IgM levels were measured.Linear regression,quantile-based g-computation(QGC),and Bayesian kernel machine regression(BKMR)models were used to evaluate the associations.Compared with the first tertile of metal levels,arsenic(As)was negatively associated with IgE(β=-0.25,95%confidence interval(CI)=-0.48 to-0.02).Moreover,significant associations of manganese(Mn)with IgA,IgG and IgM were demonstrated(β=0.10,95%CI=0.04 to 0.18;β=0.07,95%CI=0.03 to 0.12;β=0.10,95%CI=0.03 to 0.18,respectively).Cadmium(Cd)were associated with higher levels of IgM.QGC models showed the positive association of the metalmixtures with IgA and IgG,with Mn playing amajor role.Mn and Cd had positive contributions to IgM,while As had negative contributions to IgE.In the BKMR models,the latent continuous outcomes of IgA and IgG showed a significant increase when all the metals were at their 60th percentile or above compared to those at their 50th percentile.Therefore,exposure to metals was associated with maternal Igs,and mainly showed that Mn was associated with increased levels of IgA,IgG and IgM,and As was associated with low IgE levels.展开更多
BACKGROUND The exact mechanisms underlying diabetic nephropathy(DN)remain incompletely elucidated,prompting researchers to explore new perspectives and identify novel intervention targets in this field.AIM To explore ...BACKGROUND The exact mechanisms underlying diabetic nephropathy(DN)remain incompletely elucidated,prompting researchers to explore new perspectives and identify novel intervention targets in this field.AIM To explore the role and underlying mechanisms of farnesoid X receptor(FXR)in the development of DN by regulating endoplasmic reticulum stress(ERS)molecular chaperone binding immunoglobulin protein(BiP)expression.METHODS Bioinformatics analyses identified potential FXR-binding elements in the BiP promoter.Dual-luciferase and chromatin immunoprecipitation(ChIP)assays confirmed FXR-BiP binding sites.In vitro studies used SV40 MES 13 cells under varying glucose conditions and treatments with FXR modulators[obeticholic acid(INT-747)and guggulsterones]or BiP small interfering RNA.The expression of BiP and ERS-related proteins[protein kinase R-like endoplasmic reticulum kinase(PERK),inositol-requiring enzyme 1(IRE1),activating transcription factor 6(ATF6)]was assessed alongside cell proliferation and extracellular matrix(ECM)synthesis.In vivo studies in DN mice(db/db)examined the effects of FXR activation on renal function and morphology.RESULTS FXR bound to the target sequence in the BiP promoter region,enhancing transcriptional activity,as confirmed by ChIP experiments.FXR expression decreased in SV40 MES 13 cells stimulated with high glucose and in renal tissues of DN mice compared with control.Treatment of SV40 MES 13 cells with the FXR agonist INT-747 significantly increased intracellular BiP expression,whereas silencing the FXR gene led to the downregulation of BiP levels.In vivo administration of INT-747 significantly elevated BiP levels in renal tissues,improved renal function and fibrosis in DN mice,while inhibiting the expression of ERS-related signaling proteins PERK,IRE1,and ATF6.CONCLUSION FXR promotes BiP expression by binding to its promoter,suppressing ERS pathways,and reducing mesangial cell proliferation and ECM synthesis.These findings highlight FXR as a potential therapeutic target for diabetic glomerulosclerosis.展开更多
BACKGROUND Immunoglobulin G4(IgG4)-related disease(IgG4-RD),a relatively rare immunemediated chronic inflammatory condition characterized by fibrosis,is capable of affecting multiple organs and systems.Epidemiological...BACKGROUND Immunoglobulin G4(IgG4)-related disease(IgG4-RD),a relatively rare immunemediated chronic inflammatory condition characterized by fibrosis,is capable of affecting multiple organs and systems.Epidemiologically,the disease predominantly affects middle-aged and older men in Asian populations,whereas it shows a female predominance in the corresponding age group in the United States.In IgG4-RD,affected tissues and organs may exhibit diffuse or localized swelling,mimicking neoplastic lesions.IgG4-related cholecystitis(IgG4-CC)represents a manifestation involving the gallbladder,with isolated gallbladder involvement without other organ lesions being exceptionally uncommon.CASE SUMMARY A 53-year-old man was admitted to the hospital with abdominal pain.Preoperative evaluations could not exclude gallbladder carcinoma,and surgical intervention was required.Based on intraoperative findings,postoperative pathology,and postoperative serum IgG4 levels,a diagnosis of IgG4-CC was considered.After glucocorticoid therapy,the patient’s general condition substantially improved.CONCLUSION For patients present with space-occupying lesions of the gallbladder,IgG4-RD should be included in the differential diagnosis.展开更多
BACKGROUND Immunoglobulin A nephropathy is a leading cause of primary glomerulonephritis globally.Predicting disease progression using clinical markers alone is often inadequate.Integrating the Oxford classification m...BACKGROUND Immunoglobulin A nephropathy is a leading cause of primary glomerulonephritis globally.Predicting disease progression using clinical markers alone is often inadequate.Integrating the Oxford classification may enhance kidney survival predictions,though its relevance in Pakistan remains unexplored.AIM To determine the correlation between MEST-C scores and clinical parameters,as well as their utility in predicting long-term kidney outcomes.METHODS A retrospective analysis was conducted on biopsy-confirmed immunoglobulin A nephropathy cases diagnosed from 1998 to 2019 at the Sindh Institute of Urology and Transplantation,with a minimum follow-up of 12 months.RESULTS Among 118 patients(mean age:29.03±10.58 years),median proteinuria was 2.13 g/day,and mean estimated glomerular filtration rate(eGFR)was 67.82±44.60 mL/minute/1.73 m^(2).Upon admission,26.4%required kidney replacement therapy.Oxford classification components(E1,T1/T2,C1/C2)were significantly linked to proteinuria and eGFR decline(P=0.00).Remission rates were 79.6%,77.9%,77.1%,49.3%,and 33.3%at 6 months,and at 1 year,2 years,5 years,and 10 years,respectively.End-stage kidney disease progression increased over time,reaching 20.3%,22%,22.8%,31.3%,and 33.8%at 6 months,1 year,2 years,5 years,and 10 years,respectively.Three(2.5%)patients died.The median follow-up was 3.5 years;kidney survival rates were 79.6%,77.9%,77.1%,49.3%and 33.3%at 6 months and at 1 year,2 years,5 years,and 10 years,respectively.Higher MEST-C scores and lower baseline eGFR were associated with poorer kidney survival(log-rank P=0.00),while no significant correlation was observed with the degree of proteinuria(log-rank P=0.26).CONCLUSION The E1,T1/2,and C1/C2 components of the MEST-C score showed strong correlations with baseline clinical markers.Delayed diagnosis has led to poor long-term kidney outcomes.展开更多
BACKGROUND Immunoglobulin A(IgA)vasculitis,formerly known as Henoch-Schönlein purpura,is a small vessel vasculitis predominantly affecting children.It commonly presents with a triad of purpuric rash,arthralgia,an...BACKGROUND Immunoglobulin A(IgA)vasculitis,formerly known as Henoch-Schönlein purpura,is a small vessel vasculitis predominantly affecting children.It commonly presents with a triad of purpuric rash,arthralgia,and abdominal pain.However,dermatologic manifestations of IgA vasculitis in black-skinned individuals are poorly documented in literature.CASE SUMMARY This case report describes an 11-year-old black girl with acute onset of rash,joint pain,and abdominal pain,subsequently diagnosed with IgA vasculitis.CONCLUSION The case highlights the importance of early recognition and supportive management in ensuring a favorable outcome,particularly in dark-skinned populations.展开更多
Heparin-induced thrombocytopenia(HIT) is a relatively infrequent complication of heparin administration. HIT can cause devastating thrombosis, making it one of the most serious adverse drug reactions encountered in cl...Heparin-induced thrombocytopenia(HIT) is a relatively infrequent complication of heparin administration. HIT can cause devastating thrombosis, making it one of the most serious adverse drug reactions encountered in clinical practice. We successfully treated a case of severe HIT presenting with thrombosis and life-threatening bleeding complications with intravenous immunoglobulin(IVIG), platelet transfusion and oral anticoagulant Rivaroxaban. In this case, we considered that IVIG played the most important role by preventing further thrombosis, increasing the platelet count, and ensuring the efficacy of Rivaroxaban. We therefore suggest that IVIG might be the optimal treatment for patients with this urgent condition.展开更多
IgG4相关性疾病(immunoglobulin-G4 related disease,IgG4-RD)是一种免疫介导的慢性纤维炎性疾病,可累及多个系统及器官。目前IgG4-RD合并恶性肿瘤且累及同一部位的病例鲜有报道。本文报道1例72岁男性患者,以肾脏肿瘤入院,结合镜检、免...IgG4相关性疾病(immunoglobulin-G4 related disease,IgG4-RD)是一种免疫介导的慢性纤维炎性疾病,可累及多个系统及器官。目前IgG4-RD合并恶性肿瘤且累及同一部位的病例鲜有报道。本文报道1例72岁男性患者,以肾脏肿瘤入院,结合镜检、免疫表型及血清学测定最终诊断为肾透明细胞肾细胞癌合并IgG4-RD。由于IgG4-RD缺少临床特异性,容易在诊治过程中被忽略,本例意在提示IgG4-RD与肿瘤同时存在的可能性,且两者之间的发生可能存在相关性,为诊断及研究提供新的思路,避免漏诊及误诊。展开更多
文摘BACKGROUND Although breast milk is ideal for newborns,in some cases,it is replaced with cow’s milk,which contains proteins that increase the risk of cow’s milk protein allergy(CMPA).AIM To evaluate CMPA prevalence in Bahrain and compare clinical characteristics of children with immunoglobulin E(IgE)-and non-IgE-mediated CMPA.METHODS This retrospective cohort study examined children with CMPA diagnosed at the pediatric gastroenterology outpatient clinic of the Salmaniya Medical Complex,Bahrain,between 2014 and 2022,and assessed CMPA prevalence.Clinical presentations,laboratory findings,dietary modifications,and outcomes were compared between children with IgE-mediated and non-IgE-mediated CMPA.Categorical variables were compared using Fisher’s exact test or Pearson’sχ2 test,whereas continuous variables were compared using Student’s t-test or the Mann-Whitney U test.RESULTS Of 8332 patients,6022(72.3%)adhered to their appointment.Of them,618(10.3%)were suggested of having CMPA and 595(96.3%)were included;CMPA prevalence was 2%.Most patients were Bahraini(93.8%)and males(55.3%).Non-IgE-mediated type accounted for 77.3%cases and IgE-mediated type,22.7%.IgE-mediated CMPA presented more in boys(P=0.030),and later in life(5.1 months±4.5 months vs 4.2 months±4.2 months,P=0.016,95%CI:0.08-1.73),had more associated diseases(P<0.001);and presented with more cutaneous(P=0.024)and respiratory(P=0.003)manifestations,severe symptoms[rash/dry skin(P=0.031),facial swelling/angioedema(P=0.003),failure to thrive(P=0.013),apparent life-threatening event(P<0.001)],and positive physical findings(P=0.002)than non-IgE-mediated CMPA.Most patients were exclusively fed cow milk formula(50.3%).The amino acid-based formula(AAF)was most prescribed(60.5%)with no difference between the two types(P=0.173).Although breastfeeding was recommended to 49.6%,only 8.2%were exclusively breastfed.IgE-mediated CMPA was associated with a longer follow-up duration than non-IgE-mediated CMPA(17.3 months±14.0 months vs 13.5 months±13.4 months,P=0.005,95%CI:1.1-6.3).CONCLUSION This study revealed a high CMPA prevalence with clinical differences between both types that can influence treatment.AAF was most prescribed,while breastfeeding with dietary modification is rarely applied.
文摘BACKGROUND Coronavirus disease 2019(COVID-19)pneumonia with severe septic shock and acute respiratory distress syndrome(ARDS)are critical illnesses for patients following transplant.Intravenous immunoglobulin(IVIG)plays a role in both immune support and inflammation control,especially in immunocompromised patients.This case report describes the first successful experience using IVIG and pulse steroids to manage this critical condition following lung transplantation.CASE SUMMARY A 65-year-old male patient reported a history of chronic obstructive pulmonary disease and poor lung function and received bilateral sequential lung transplantations.Postoperatively,he developed COVID-19 pneumonia,severe septic shock,and ARDS.He recovered from this critical condition after empirical antibiotics administration and veno-venous extracorporeal membrane oxygenation,in addition to IVIG and pulse steroids.CONCLUSION IVIG is a valuable adjunct in managing severe sepsis in lung transplant recipients after COVID-19 infection.We aim,for the first time,to report the success of such a management approach for COVID-19 ARDS and sepsis in the post-lung transplant setting.With further investigations,this is a starting point for wider analysis of such an approach in this setting and consequently helps guide clinical practice for such a challenging patient population moving forward.
基金supported by Austrian Federal Ministry for Digital and Economic Affairsthe National Foundation for Research,Technology and Developmentsupported using resources of the Vet Core Facility(Mass Spectrometry)of the University of Veterinary Medicine Vienna。
文摘Background The objective was to characterize the colostrum proteome of primiparous Holstein cows in association with immunoglobulin G(IgG)content.Immediately after calving,colostrum samples were collected from 18 cows to measure IgG concentration.Based on colostrum IgG content,samples were classified through cluster analysis and were identified as poor,average,and excellent quality.The proteome was assessed with quantitative shotgun proteomics;abundance data were compared among the colostrum types;enrichment analysis of metabolic processes and proteins classes was performed as well.We also tested correlations between this proteome and blood globulin level of cows and passive immunity level of calves.Results On average,428 proteins were identified per sample,which belonged mainly to cellular process,biological regulation,response to stimulus,metabolic process,and immune system process.Most abundant proteins were complement C3(Q2UVX4),alpha-S1-casein(P02662),Ig-like domain-containing protein(A0A3Q1M032),albumin(A0A140T897),polymeric immunoglobulin receptor(P81265),lactotransferrrin(P24627),and IGHG1*01(X167014).Colostrum of excellent quality had greater(P<0.05)abundance of serpin A3-7(A2I7N3),complement factorl(A0A3Q1 MIF4),lipocalin/cytosolic fatty-acid binding domain-containing protein(A0A3Q1 MRQ2),complement C3(E1B805),complement component 4 binding protein alpha(A0AAF6ZHP5),and complement component C6(F1MM86).However,colostrum of excellent quality had lower(P<0.05)abundance of HGF activator(E1BCW0),alpha-S1-casein(P02662),and xanthine dehydrogenase/oxidase(P80457).This resulted in enrichment of the biological processes predominantly for complement activation alternative pathway,complement activation,complement activation classical pathway,humoral immune response,leukocyte mediated immunity,and negative regulation of endopeptidase activity in excellent-quality colostrum.Additionally,some colostrum proteins were found to be correlated with the blood globulin level of cows and with the passive immunity level of calves(P<0.05;r≥0.57).Conclusions This study provides new insights into the bovine colostrum proteome,demonstrating associations between IgG levels and the abundance of other proteins,as well as the enrichment of metabolic processes related to innate immune response.Thus,results suggest that the colostrum proteomic profile is associated with the content of IgG.Future research should deeply explore the association of these findings with pre-calving nutrition status and blood composition of the cow,and with passive immunity transfer to the calf.
基金supported by the National Natural Science Foundation of China(Grant Nos.12222506,12347102,and 12174184).
文摘Understanding the liquid-liquid phase separation(LLPS)of immunoglobulin G(IgG)is crucial,as it profoundly influences IgG’s biological activity and stability.In this study,we employed coarse-grained molecular dynamics simulations to systematically investigate the phase separation behavior of IgG.We first constructed two types of IgG models:all-pair IgG model and partial-pair IgG model,and compared the coexistence curve from our simulations with experimental data.Our results showed that the partial-pair IgG model aligns better with the experimental critical temperature and critical density.Using this model,we then calculated the temperature-dependent variations of IgG’s radius of gyration,surface tension,viscosity,etc.More importantly,we demonstrated that variations in the interaction strengths among IgG molecules significantly influence their phase separation behavior.Specifically,a higher standard deviation of interaction strength at different temperatures is found to lead to more stable phase-separated states.Furthermore,we observed that the introduction of repulsive polymers and strongly attractive polymers consistently enhances IgG phase separation,while weakly attractive polymers exhibit a dual regulatory effect on the phase separation.Overall,this study provides valuable insights into the mechanisms governing IgG phase behavior,with potential implications for optimizing biopharmaceutical products.
文摘Immunoglobulin(Ig)A nephropathy is the most common type of primary glomerulonephritis globally.It typically manifests with microscopic hematuria and a spectrum of proteinuria,although rapidly progressive glomerulonephritis may occur in rare instances.Deposition of IgA in the mesangium seems to be the underlying disease mechanism.Despite current treatment,IgA nephropathy may progress into end-stage renal disease,indicating the necessity for the development of new therapeutic agents.Lifestyle modifications and anti-proteinuric treatment are recommended,and steroids have shown to be beneficial to high risk groups.Nevertheless,other conventional immunosuppressive agents,such as cyclophosphamide and mycophenolate mofetil,may be considered,despite the lack of sufficient evidence to support their efficacy.A considerable proportion of cases remain unresponsive to these treatments,underscoring the need for novel therapeutic approaches.There are several promising immunosuppressive drugs,such as B-cell lineage depleting agents or complement system inhibitors,that are currently undergoing clinical trials.These therapies may be considered for use in selected cases.
基金supported by the National Natural Science Foundation of China(No.U22A20358)Zhejiang Provincial Program for the Cultivation of High-Level Innovative Health Talents(No.2020-18).
文摘Metal may affect maternal immune function,but few epidemiological studies have reported the associations between multiple-metal exposure and maternal immunoglobulin(Ig)levels.Based on the Hangzhou Birth Cohort Study,1059 participants were included,and eleven metals in whole blood samples and serum IgA,IgG,IgE and IgM levels were measured.Linear regression,quantile-based g-computation(QGC),and Bayesian kernel machine regression(BKMR)models were used to evaluate the associations.Compared with the first tertile of metal levels,arsenic(As)was negatively associated with IgE(β=-0.25,95%confidence interval(CI)=-0.48 to-0.02).Moreover,significant associations of manganese(Mn)with IgA,IgG and IgM were demonstrated(β=0.10,95%CI=0.04 to 0.18;β=0.07,95%CI=0.03 to 0.12;β=0.10,95%CI=0.03 to 0.18,respectively).Cadmium(Cd)were associated with higher levels of IgM.QGC models showed the positive association of the metalmixtures with IgA and IgG,with Mn playing amajor role.Mn and Cd had positive contributions to IgM,while As had negative contributions to IgE.In the BKMR models,the latent continuous outcomes of IgA and IgG showed a significant increase when all the metals were at their 60th percentile or above compared to those at their 50th percentile.Therefore,exposure to metals was associated with maternal Igs,and mainly showed that Mn was associated with increased levels of IgA,IgG and IgM,and As was associated with low IgE levels.
基金Supported by the Talent Launch Fund of Chongqing Medical University Affiliated University City HospitalChongqing Medical University Affiliated University City Hospital Youth Program,No.2021ZD05.
文摘BACKGROUND The exact mechanisms underlying diabetic nephropathy(DN)remain incompletely elucidated,prompting researchers to explore new perspectives and identify novel intervention targets in this field.AIM To explore the role and underlying mechanisms of farnesoid X receptor(FXR)in the development of DN by regulating endoplasmic reticulum stress(ERS)molecular chaperone binding immunoglobulin protein(BiP)expression.METHODS Bioinformatics analyses identified potential FXR-binding elements in the BiP promoter.Dual-luciferase and chromatin immunoprecipitation(ChIP)assays confirmed FXR-BiP binding sites.In vitro studies used SV40 MES 13 cells under varying glucose conditions and treatments with FXR modulators[obeticholic acid(INT-747)and guggulsterones]or BiP small interfering RNA.The expression of BiP and ERS-related proteins[protein kinase R-like endoplasmic reticulum kinase(PERK),inositol-requiring enzyme 1(IRE1),activating transcription factor 6(ATF6)]was assessed alongside cell proliferation and extracellular matrix(ECM)synthesis.In vivo studies in DN mice(db/db)examined the effects of FXR activation on renal function and morphology.RESULTS FXR bound to the target sequence in the BiP promoter region,enhancing transcriptional activity,as confirmed by ChIP experiments.FXR expression decreased in SV40 MES 13 cells stimulated with high glucose and in renal tissues of DN mice compared with control.Treatment of SV40 MES 13 cells with the FXR agonist INT-747 significantly increased intracellular BiP expression,whereas silencing the FXR gene led to the downregulation of BiP levels.In vivo administration of INT-747 significantly elevated BiP levels in renal tissues,improved renal function and fibrosis in DN mice,while inhibiting the expression of ERS-related signaling proteins PERK,IRE1,and ATF6.CONCLUSION FXR promotes BiP expression by binding to its promoter,suppressing ERS pathways,and reducing mesangial cell proliferation and ECM synthesis.These findings highlight FXR as a potential therapeutic target for diabetic glomerulosclerosis.
基金Supported by the National Natural Science Foundation of Shandong Province,No.ZR2019QH008.
文摘BACKGROUND Immunoglobulin G4(IgG4)-related disease(IgG4-RD),a relatively rare immunemediated chronic inflammatory condition characterized by fibrosis,is capable of affecting multiple organs and systems.Epidemiologically,the disease predominantly affects middle-aged and older men in Asian populations,whereas it shows a female predominance in the corresponding age group in the United States.In IgG4-RD,affected tissues and organs may exhibit diffuse or localized swelling,mimicking neoplastic lesions.IgG4-related cholecystitis(IgG4-CC)represents a manifestation involving the gallbladder,with isolated gallbladder involvement without other organ lesions being exceptionally uncommon.CASE SUMMARY A 53-year-old man was admitted to the hospital with abdominal pain.Preoperative evaluations could not exclude gallbladder carcinoma,and surgical intervention was required.Based on intraoperative findings,postoperative pathology,and postoperative serum IgG4 levels,a diagnosis of IgG4-CC was considered.After glucocorticoid therapy,the patient’s general condition substantially improved.CONCLUSION For patients present with space-occupying lesions of the gallbladder,IgG4-RD should be included in the differential diagnosis.
文摘BACKGROUND Immunoglobulin A nephropathy is a leading cause of primary glomerulonephritis globally.Predicting disease progression using clinical markers alone is often inadequate.Integrating the Oxford classification may enhance kidney survival predictions,though its relevance in Pakistan remains unexplored.AIM To determine the correlation between MEST-C scores and clinical parameters,as well as their utility in predicting long-term kidney outcomes.METHODS A retrospective analysis was conducted on biopsy-confirmed immunoglobulin A nephropathy cases diagnosed from 1998 to 2019 at the Sindh Institute of Urology and Transplantation,with a minimum follow-up of 12 months.RESULTS Among 118 patients(mean age:29.03±10.58 years),median proteinuria was 2.13 g/day,and mean estimated glomerular filtration rate(eGFR)was 67.82±44.60 mL/minute/1.73 m^(2).Upon admission,26.4%required kidney replacement therapy.Oxford classification components(E1,T1/T2,C1/C2)were significantly linked to proteinuria and eGFR decline(P=0.00).Remission rates were 79.6%,77.9%,77.1%,49.3%,and 33.3%at 6 months,and at 1 year,2 years,5 years,and 10 years,respectively.End-stage kidney disease progression increased over time,reaching 20.3%,22%,22.8%,31.3%,and 33.8%at 6 months,1 year,2 years,5 years,and 10 years,respectively.Three(2.5%)patients died.The median follow-up was 3.5 years;kidney survival rates were 79.6%,77.9%,77.1%,49.3%and 33.3%at 6 months and at 1 year,2 years,5 years,and 10 years,respectively.Higher MEST-C scores and lower baseline eGFR were associated with poorer kidney survival(log-rank P=0.00),while no significant correlation was observed with the degree of proteinuria(log-rank P=0.26).CONCLUSION The E1,T1/2,and C1/C2 components of the MEST-C score showed strong correlations with baseline clinical markers.Delayed diagnosis has led to poor long-term kidney outcomes.
文摘BACKGROUND Immunoglobulin A(IgA)vasculitis,formerly known as Henoch-Schönlein purpura,is a small vessel vasculitis predominantly affecting children.It commonly presents with a triad of purpuric rash,arthralgia,and abdominal pain.However,dermatologic manifestations of IgA vasculitis in black-skinned individuals are poorly documented in literature.CASE SUMMARY This case report describes an 11-year-old black girl with acute onset of rash,joint pain,and abdominal pain,subsequently diagnosed with IgA vasculitis.CONCLUSION The case highlights the importance of early recognition and supportive management in ensuring a favorable outcome,particularly in dark-skinned populations.
文摘Heparin-induced thrombocytopenia(HIT) is a relatively infrequent complication of heparin administration. HIT can cause devastating thrombosis, making it one of the most serious adverse drug reactions encountered in clinical practice. We successfully treated a case of severe HIT presenting with thrombosis and life-threatening bleeding complications with intravenous immunoglobulin(IVIG), platelet transfusion and oral anticoagulant Rivaroxaban. In this case, we considered that IVIG played the most important role by preventing further thrombosis, increasing the platelet count, and ensuring the efficacy of Rivaroxaban. We therefore suggest that IVIG might be the optimal treatment for patients with this urgent condition.
文摘IgG4相关性疾病(immunoglobulin-G4 related disease,IgG4-RD)是一种免疫介导的慢性纤维炎性疾病,可累及多个系统及器官。目前IgG4-RD合并恶性肿瘤且累及同一部位的病例鲜有报道。本文报道1例72岁男性患者,以肾脏肿瘤入院,结合镜检、免疫表型及血清学测定最终诊断为肾透明细胞肾细胞癌合并IgG4-RD。由于IgG4-RD缺少临床特异性,容易在诊治过程中被忽略,本例意在提示IgG4-RD与肿瘤同时存在的可能性,且两者之间的发生可能存在相关性,为诊断及研究提供新的思路,避免漏诊及误诊。
