BACKGROUND Primary Sjögren's syndrome(pSS)concomitant with autoimmune hemolytic anemia(AIHA)but without eye and mouth dryness is exceedingly rare.Iguratimod(IGU)has been widely used in the treatment of pSS.Ho...BACKGROUND Primary Sjögren's syndrome(pSS)concomitant with autoimmune hemolytic anemia(AIHA)but without eye and mouth dryness is exceedingly rare.Iguratimod(IGU)has been widely used in the treatment of pSS.However,there are few reports about the application of IGU in pSS concomitant with AIHA.CASE SUMMARY Here,we present the case of a patient with pSS concomitant with AIHA but without eye and mouth dryness.The patient was initially diagnosed with hyperplastic anemia and AIHA while pSS was missed,and was finally diagnosed with pSS concomitant with AIHA.The patient was treated with IGU along with prednisone and hydroxychloroquine,and her hemoglobin,reticulocytes and IgG returned to normal levels.CONCLUSION IGU was effective for and well tolerated by our patient with pSS concomitant with AIHA,and may be a promising therapy for the treatment of this disease.展开更多
BACKGROUND The association of Sjögren's syndrome(SS)and lymphoma is similar.Mucosaassociated lymphoid tissue(MALT)or extranodal marginal zone B-cell lymphoma was the most common lymphomatous histology in SS p...BACKGROUND The association of Sjögren's syndrome(SS)and lymphoma is similar.Mucosaassociated lymphoid tissue(MALT)or extranodal marginal zone B-cell lymphoma was the most common lymphomatous histology in SS patients.MALT in SS patients is frequently located in the parotid gland,while MALT lymphoma of the skin with SS is an exceedingly rare entity that needs to be recognized.CASE SUMMARY A 60-year-old woman presented with a 3-year history of progressive dry mouth associated with a 1-year history of enlarging cutaneous nodules.Physical examination revealed two hard subcutaneous nodules on her right lower leg.The results of Schirmer’s test were positive,despite the absence of dry eyes.Labial salivary gland biopsy revealed lymphocytic infiltration and chronic inflammation with a focus score of 2.The patient was diagnosed with SS.She underwent resection of one cutaneous nodule,and histopathological analysis identified the nodule as MALT lymphoma.Her dry mouth symptoms improved,and the nodules decreased after 6 mo of treatment with hydroxychloroquine sulfate and chemotherapy(thalidomide,cyclophosphamide,and dexamethasone).CONCLUSION Lymphoma is a severe complication of SS,shown by the reported unique case of cutaneous MALT lymphoma with SS.展开更多
<div style="text-align:justify;"> <span style="font-family:Verdana;"><strong>Background:</strong> The association of primary Sj<span style="white-space:nowrap;"...<div style="text-align:justify;"> <span style="font-family:Verdana;"><strong>Background:</strong> The association of primary Sj<span style="white-space:nowrap;">ö</span>gren syndrome (PSS) and AA amyloidosis is a rare occurrence. <strong>Objective: </strong>To describe the phenotype of patients with this association through our two cases and a literature review. <strong>Materials and methods:</strong> A report of two cases of AA amyloidosis complicating primary Sj<span style="white-space:nowrap;">ö</span>gren syndrome with a literature review. <strong>Results:</strong> Eight patients of Primary Sj<span style="white-space:nowrap;">ö</span>gren’s Syndrome complicated by AA amyloidosis were studies. Six cases were reported in the literature by consulting several databases. 50% of patients had a positive immunological assessment, three cases with kidney damage, and three cases lung damage. <strong>Conclusion: </strong>The immunological activity in the Primary Sjogren’s Syndrome requires the search not only a lymphoma but also AA amyloidosis apart from any clinical or biological chronic inflammation.</span> </div>展开更多
Primary Sjögren’s syndrome(pSS)is a systemic autoimmune disease with high prevalence and possible poor prognosis.Though the pathogenesis of pSS has not been fully elucidated,B cell hyperactivity is considered as...Primary Sjögren’s syndrome(pSS)is a systemic autoimmune disease with high prevalence and possible poor prognosis.Though the pathogenesis of pSS has not been fully elucidated,B cell hyperactivity is considered as one of the fundamental abnormalities in pSS patients.It has long been identified that Janus kinases-signal transducer and activator of transcription(JAK-STAT)signaling pathway contributes to rheumatoid arthritis and systemic lupus erythematosus.Recently,increasing numbers of studies have provided evidence that JAK-STAT pathway also has an important role in the pathogenesis of pSS via direct or indirect activation of B cells.Signal transducer and activator of transcription 1(STAT1),STAT3,and STAT5 activated by various cytokines and ribonucleic acid contribute to pSS development,respectively or synergically.These results reveal the potential application of Janus kinase inhibitors for treatment of pSS,which may fundamentally improve the quality of life and prognosis of patients with pSS.展开更多
Background:Primary biliary cholangitis(PBC)patients often have concomitant extrahepatic autoimmune(EHA)diseases including Sjögren’s syndrome(SS),systemic sclerosis(SSc),rheumatoid arthritis(RA),and autoimmune th...Background:Primary biliary cholangitis(PBC)patients often have concomitant extrahepatic autoimmune(EHA)diseases including Sjögren’s syndrome(SS),systemic sclerosis(SSc),rheumatoid arthritis(RA),and autoimmune thyroid disease.The present study aimed to describe the prevalence of EHA diseases in PBC and explore the impact of EHA diseases on the long-term outcomes of PBC in Chinese patients.Methods:Medical records of PBC patients diagnosed in our institute were retrospectively reviewed.Pa-tients were followed up by a standardized telephone interview.The endpoints were defined as liver-related death and/or liver transplantation.Results:Totally 247 of the 985(25.1%)PBC patients enrolled in the study had at least one concomi-tant EHA disease.Sjögren’s syndrome(n=140,14.2%)was the most frequent one,followed by rheuma-toid arthritis(RA)(n=56,5.7%)and Hashimoto’s thyroiditis(n=45,4.6%).Patients with EHA dis-eases were more common in females(P<0.001)and in those with a family history of autoimmune disease(P=0.017).Overall,no differences were found between PBC patients with and without EHA dis-eases in terms of biochemical response rates to ursodeoxycholic acid,the incidence of hepatic events,or transplant-free survival.RA and EHA≥2 were protective factors for hepatic events in univariate Cox analysis,but the results became insignificant in multivariate analysis.Conclusions:Concomitant EHA diseases were common in PBC patients but did not compromise the long-term outcomes of PBC.展开更多
目的:探讨着丝点蛋白B(centromere protein B,CENP-B)抗体阳性的原发性干燥综合征(primary Sj9gren’s syndrome,pSS)患者的临床和免疫学特征。方法:采用横断面研究的研究设计,回顾性纳入2016年1月至2022年8月就诊于北京大学口腔医院并...目的:探讨着丝点蛋白B(centromere protein B,CENP-B)抗体阳性的原发性干燥综合征(primary Sj9gren’s syndrome,pSS)患者的临床和免疫学特征。方法:采用横断面研究的研究设计,回顾性纳入2016年1月至2022年8月就诊于北京大学口腔医院并确诊为pSS的患者,收集分析患者的一般及临床特征、唾液腺造影、唇腺活检病理、血清免疫学及生化检查等资料。将pSS患者分为CENP-B抗体阳性组和阴性组,用SPSS 23.0软件对数据进行描述性分析、单因素及相关性分析,并将CENP-B抗体阳性组分为CENP-B抗体单阳性组及合并其他抗体阳性组进行亚组分析。结果:共纳入288例pSS患者,其中CENP-B抗体阳性组75例(26.0%),阴性组213例(74.0%)。CENP-B抗体阳性组的发病年龄较大,罹患自身免疫性肝病的比例较高,唾液腺肿大的比例较低,SSA/Ro60、Ro52、SSB抗体的阳性率均较低,免疫球蛋白G、类风湿因子的水平较低,免疫球蛋白M的水平较高,总蛋白水平较低,而白蛋白/球蛋白比值、谷丙转氨酶、谷草转氨酶、碱性磷酸酶、γ-谷氨酰转移酶、乳酸脱氢酶的水平较高。亚组分析显示,CENP-B抗体单阳性组的总蛋白、免疫球蛋白A水平低于合并其他抗体阳性组。结论:CENP-B抗体阳性的pSS患者具有独特的临床和免疫学特征,表现为疾病活动性较低,较少发生唾液腺肿大,但易罹患自身免疫性肝病,肝功能生化指标水平偏高,提示CENP-B抗体可能是pSS亚型分类的特异性标志物。展开更多
Background Traditional Chinese medical treatment of primary Sj(o)gren's syndrome has advantages over Western medicine in terms of fewer side effects and improved patient conditions.This study was a multicenter,rand...Background Traditional Chinese medical treatment of primary Sj(o)gren's syndrome has advantages over Western medicine in terms of fewer side effects and improved patient conditions.This study was a multicenter,randomized,doubleblind,placebo-controlled clinical trial of the efficacy and safety of ShengJinRunZaoYangXue granules for the treatment of primary Sj(o)gren's syndrome,including the symptoms of dry mouth and dry eye.Methods We undertook a 6-week,double-blind,randomized trial involving 240 patients with primary Sj(o)gren's syndrome at five centers in East China.A computer-generated randomization schedule assigned patients at a 2∶1 ratio to receive either ShengJinRunZaoYangXue granules or placebo once daily.Patients and investigators were blinded to treatment allocation.The primary endpoints were the salivary flow rate,Schirmer test results,and sugar test results.Intention-to-treat and per-protocol analyses were performed.Results All 240 patients were randomly allocated to either the treatment group (n=160,ShengJinRunZaoYangXue granules) or placebo group (n=80) and were included in the intention-to-treat analysis.After program violation and loss to follow-up,a total of 199 patients were included in the per-protocol analysis.At six week,intention-to-treat and per-protocol analyses of the left-eye Schirmer I test results showed an improved difference of 1.36 mm/5 min (95% CI:0.03 to 2.69 mm/5 min) and 1.35 mm/5 min (95% CI:0.04 to 2.73 mm/5 min),respectively,and those of the right-eye Schirmer I test results showed an improved difference of 1.12 mm/5 min (95% CI:0.02 to 2.22 mm/5 min) and 1.12 mm/5 min (95% CI:-0.02 to 2.27 mm/5 min),respectively.There was no significant difference between the two groups before treatment.After treatment,the between-group and within-group before-and-after paired comparison results were statistically significant (P 〈0.05).Intention-to-treat and per-protocol analyses showed an improved salivary flow rate by 0.04 ml/15 min (95% CI:-0.49 to 0.58 ml/15 min) and 0.04 ml/15 min (95% CI:-0.52 to 0.60 ml/15 min),respectively,but the differences were not significant.Intention-to-treat and per-protocol analyses showed that the sugar test results were improved by 1.77 minutes (95% CI:0.11 to 3.44 minutes) and 1.84 minutes (95% CI:0.12 to 3.55 minutes),respectively,but the differences were not significant.For the secondary endpoint,intention-to-treat and per-protocol analyses showed significant improvement in the integrated evaluation of treated patients with dry eye and dry mouth after six weeks of treatment.The incidence of adverse events was 15.6% in the treatment group and 10.0% in the placebo group.Most (94%) adverse events were mild to moderate in the two groups,and only two cases of serious adverse events occurred in the treatment group; both were caused by autoimmune liver disease.Conclusions Six-week treatment with ShengJinRunZaoYangXue granules for primary Sj(o)gren's syndrome in this large-scale study improved the symptoms of dry mouth,dry eyes,and low tear flow rate with minimal adverse events.展开更多
Increased numbers of T follicular helper(Tfh)cells have been implicated in the development of autoimmune diseases including primary Sjögren’s syndrome(pSS),but how the Tfh cell response is regulated during autoi...Increased numbers of T follicular helper(Tfh)cells have been implicated in the development of autoimmune diseases including primary Sjögren’s syndrome(pSS),but how the Tfh cell response is regulated during autoimmune pathogenesis remains largely unclear.Here,we first found negative correlations between IL-10^(+)regulatory B(Breg)cell numbers and Tfh cell responses and disease activity in patients with pSS and mice with experimental Sjögren’s syndrome(ESS).Moreover,we detected high expression of IL-10 receptor on Tfh cells and their precursors in both humans and mice.In culture,IL-10 suppressed human and murine Tfh cell differentiation by promoting STAT5 phosphorylation.By using an adoptive transfer approach and two-photon live imaging,we found significantly increased numbers of Tfh cells with enhanced T cell homing into B cell follicles in the draining cervical lymph nodes of RAG-2−/−mice transferred with IL-10-deficient B cells during ESS development compared with those of RAG-2−/−mice transferred with wild-type B cells.In ESS mice,CD19^(+)CD1d^(hi)CD5^(+)Breg cells with decreased IL-10 production exhibited severely impaired suppressive effects on T cell proliferation.Consistently,CD19^(+)CD24^(+)CD38^(hi) Breg cells from pSS patients showed significantly reduced IL-10 production with defective inhibitory function in the suppression of autologous Tfh cell expansion.Furthermore,the adoptive transfer of IL-10-producing Breg cells markedly suppressed the Tfh cell response and ameliorated ESS progression in ESS mice.Together,these findings demonstrate a critical role for IL-10-producing Breg cells in restraining the effector Tfh cell response during pSS development.展开更多
Liver involvement was one of the first extraglandular manifestations to be reported in patients with primary Sj(o)gren syndrome (SS).In the 1990s,a study of liver involvement in patients with primary SS integrated the...Liver involvement was one of the first extraglandular manifestations to be reported in patients with primary Sj(o)gren syndrome (SS).In the 1990s,a study of liver involvement in patients with primary SS integrated the evaluation of clinical signs of liver disease,liver function and a complete panel of autoantibodies.Recent developments in the field of hepatic and viral diseases have significantly changed the diagnostic approach to liver involvement in SS.The most recent studies have shown that,after eliminating hepatotoxic drugs and fatty liver disease,the two main causes of liver disease in primary SS are chronic viral infections and autoimmune liver diseases.The differential diagnosis of liver disease in primary SS (viral vs autoimmune) is clinically important,since the two processes require different therapeutic approaches and have different prognoses.With respect to viral infections,chronic HCV infection is the main cause of liver involvement in SS patients from the Mediterranean area,while chronic HBV infection may be the main cause of liver involvement in SS patients from Asian countries.After eliminating viral hepatitis,primary biliary cirrhosis (PBC) should be considered the main cause of liver disease in primary SS.PBC-related SS patients may have a broad spectrum of abnormalities of the liver,including having no clinical or analytical data suggestive of liver disease.Autoimmune hepatitis (AIH) is the second most frequently found autoimmune liver disease to be associated with SS (all reported cases are type I),and nearly 10% of these patients have an AIH-PBC overlap.Finally,IgG4-related disease must be investigated in patients with SS presenting with sclerosing cholangitis,especially when autoimmune pancreatitis or retroperitoneal fibrosis are also present.展开更多
基金Supported by the Lanzhou Science and Technology Plan Project,No.2018-3-48Lanzhou Talent Innovation and Entrepreneurship Project,No.2019-RC-35and 2019 Special Fund for Doctoral Training of Lanzhou University Second Hospital,No.YJS-BD-15.
文摘BACKGROUND Primary Sjögren's syndrome(pSS)concomitant with autoimmune hemolytic anemia(AIHA)but without eye and mouth dryness is exceedingly rare.Iguratimod(IGU)has been widely used in the treatment of pSS.However,there are few reports about the application of IGU in pSS concomitant with AIHA.CASE SUMMARY Here,we present the case of a patient with pSS concomitant with AIHA but without eye and mouth dryness.The patient was initially diagnosed with hyperplastic anemia and AIHA while pSS was missed,and was finally diagnosed with pSS concomitant with AIHA.The patient was treated with IGU along with prednisone and hydroxychloroquine,and her hemoglobin,reticulocytes and IgG returned to normal levels.CONCLUSION IGU was effective for and well tolerated by our patient with pSS concomitant with AIHA,and may be a promising therapy for the treatment of this disease.
文摘BACKGROUND The association of Sjögren's syndrome(SS)and lymphoma is similar.Mucosaassociated lymphoid tissue(MALT)or extranodal marginal zone B-cell lymphoma was the most common lymphomatous histology in SS patients.MALT in SS patients is frequently located in the parotid gland,while MALT lymphoma of the skin with SS is an exceedingly rare entity that needs to be recognized.CASE SUMMARY A 60-year-old woman presented with a 3-year history of progressive dry mouth associated with a 1-year history of enlarging cutaneous nodules.Physical examination revealed two hard subcutaneous nodules on her right lower leg.The results of Schirmer’s test were positive,despite the absence of dry eyes.Labial salivary gland biopsy revealed lymphocytic infiltration and chronic inflammation with a focus score of 2.The patient was diagnosed with SS.She underwent resection of one cutaneous nodule,and histopathological analysis identified the nodule as MALT lymphoma.Her dry mouth symptoms improved,and the nodules decreased after 6 mo of treatment with hydroxychloroquine sulfate and chemotherapy(thalidomide,cyclophosphamide,and dexamethasone).CONCLUSION Lymphoma is a severe complication of SS,shown by the reported unique case of cutaneous MALT lymphoma with SS.
文摘<div style="text-align:justify;"> <span style="font-family:Verdana;"><strong>Background:</strong> The association of primary Sj<span style="white-space:nowrap;">ö</span>gren syndrome (PSS) and AA amyloidosis is a rare occurrence. <strong>Objective: </strong>To describe the phenotype of patients with this association through our two cases and a literature review. <strong>Materials and methods:</strong> A report of two cases of AA amyloidosis complicating primary Sj<span style="white-space:nowrap;">ö</span>gren syndrome with a literature review. <strong>Results:</strong> Eight patients of Primary Sj<span style="white-space:nowrap;">ö</span>gren’s Syndrome complicated by AA amyloidosis were studies. Six cases were reported in the literature by consulting several databases. 50% of patients had a positive immunological assessment, three cases with kidney damage, and three cases lung damage. <strong>Conclusion: </strong>The immunological activity in the Primary Sjogren’s Syndrome requires the search not only a lymphoma but also AA amyloidosis apart from any clinical or biological chronic inflammation.</span> </div>
基金supported by grants from the Chinese National Key Technology R&D Program,Ministry of Science and Technology(Nos.2017YFC0907601,2017YFC0907605)CAMS Innovation Fund for Medical Sciences(CIFMS)(No.2021-I2M-1-005)
文摘Primary Sjögren’s syndrome(pSS)is a systemic autoimmune disease with high prevalence and possible poor prognosis.Though the pathogenesis of pSS has not been fully elucidated,B cell hyperactivity is considered as one of the fundamental abnormalities in pSS patients.It has long been identified that Janus kinases-signal transducer and activator of transcription(JAK-STAT)signaling pathway contributes to rheumatoid arthritis and systemic lupus erythematosus.Recently,increasing numbers of studies have provided evidence that JAK-STAT pathway also has an important role in the pathogenesis of pSS via direct or indirect activation of B cells.Signal transducer and activator of transcription 1(STAT1),STAT3,and STAT5 activated by various cytokines and ribonucleic acid contribute to pSS development,respectively or synergically.These results reveal the potential application of Janus kinase inhibitors for treatment of pSS,which may fundamentally improve the quality of life and prognosis of patients with pSS.
基金the National Natural Science Foundation of China(82000533 and 81770598).
文摘Background:Primary biliary cholangitis(PBC)patients often have concomitant extrahepatic autoimmune(EHA)diseases including Sjögren’s syndrome(SS),systemic sclerosis(SSc),rheumatoid arthritis(RA),and autoimmune thyroid disease.The present study aimed to describe the prevalence of EHA diseases in PBC and explore the impact of EHA diseases on the long-term outcomes of PBC in Chinese patients.Methods:Medical records of PBC patients diagnosed in our institute were retrospectively reviewed.Pa-tients were followed up by a standardized telephone interview.The endpoints were defined as liver-related death and/or liver transplantation.Results:Totally 247 of the 985(25.1%)PBC patients enrolled in the study had at least one concomi-tant EHA disease.Sjögren’s syndrome(n=140,14.2%)was the most frequent one,followed by rheuma-toid arthritis(RA)(n=56,5.7%)and Hashimoto’s thyroiditis(n=45,4.6%).Patients with EHA dis-eases were more common in females(P<0.001)and in those with a family history of autoimmune disease(P=0.017).Overall,no differences were found between PBC patients with and without EHA dis-eases in terms of biochemical response rates to ursodeoxycholic acid,the incidence of hepatic events,or transplant-free survival.RA and EHA≥2 were protective factors for hepatic events in univariate Cox analysis,but the results became insignificant in multivariate analysis.Conclusions:Concomitant EHA diseases were common in PBC patients but did not compromise the long-term outcomes of PBC.
文摘Background Traditional Chinese medical treatment of primary Sj(o)gren's syndrome has advantages over Western medicine in terms of fewer side effects and improved patient conditions.This study was a multicenter,randomized,doubleblind,placebo-controlled clinical trial of the efficacy and safety of ShengJinRunZaoYangXue granules for the treatment of primary Sj(o)gren's syndrome,including the symptoms of dry mouth and dry eye.Methods We undertook a 6-week,double-blind,randomized trial involving 240 patients with primary Sj(o)gren's syndrome at five centers in East China.A computer-generated randomization schedule assigned patients at a 2∶1 ratio to receive either ShengJinRunZaoYangXue granules or placebo once daily.Patients and investigators were blinded to treatment allocation.The primary endpoints were the salivary flow rate,Schirmer test results,and sugar test results.Intention-to-treat and per-protocol analyses were performed.Results All 240 patients were randomly allocated to either the treatment group (n=160,ShengJinRunZaoYangXue granules) or placebo group (n=80) and were included in the intention-to-treat analysis.After program violation and loss to follow-up,a total of 199 patients were included in the per-protocol analysis.At six week,intention-to-treat and per-protocol analyses of the left-eye Schirmer I test results showed an improved difference of 1.36 mm/5 min (95% CI:0.03 to 2.69 mm/5 min) and 1.35 mm/5 min (95% CI:0.04 to 2.73 mm/5 min),respectively,and those of the right-eye Schirmer I test results showed an improved difference of 1.12 mm/5 min (95% CI:0.02 to 2.22 mm/5 min) and 1.12 mm/5 min (95% CI:-0.02 to 2.27 mm/5 min),respectively.There was no significant difference between the two groups before treatment.After treatment,the between-group and within-group before-and-after paired comparison results were statistically significant (P 〈0.05).Intention-to-treat and per-protocol analyses showed an improved salivary flow rate by 0.04 ml/15 min (95% CI:-0.49 to 0.58 ml/15 min) and 0.04 ml/15 min (95% CI:-0.52 to 0.60 ml/15 min),respectively,but the differences were not significant.Intention-to-treat and per-protocol analyses showed that the sugar test results were improved by 1.77 minutes (95% CI:0.11 to 3.44 minutes) and 1.84 minutes (95% CI:0.12 to 3.55 minutes),respectively,but the differences were not significant.For the secondary endpoint,intention-to-treat and per-protocol analyses showed significant improvement in the integrated evaluation of treated patients with dry eye and dry mouth after six weeks of treatment.The incidence of adverse events was 15.6% in the treatment group and 10.0% in the placebo group.Most (94%) adverse events were mild to moderate in the two groups,and only two cases of serious adverse events occurred in the treatment group; both were caused by autoimmune liver disease.Conclusions Six-week treatment with ShengJinRunZaoYangXue granules for primary Sj(o)gren's syndrome in this large-scale study improved the symptoms of dry mouth,dry eyes,and low tear flow rate with minimal adverse events.
基金supported by grants from the National Natural Science Foundation of China(81771761 and 91842304)Chinese National Key Technology R&D Program,Ministry of Science and Technology(2017YFC0907601 and 2017YFC0907605)+2 种基金General Research Fund,Hong Kong Research Grants Council(17114515 and 17149716)Hong Kong Croucher Foundation(260960116)Sanming Project of Medicine in Shenzhen(SZSM201512019).
文摘Increased numbers of T follicular helper(Tfh)cells have been implicated in the development of autoimmune diseases including primary Sjögren’s syndrome(pSS),but how the Tfh cell response is regulated during autoimmune pathogenesis remains largely unclear.Here,we first found negative correlations between IL-10^(+)regulatory B(Breg)cell numbers and Tfh cell responses and disease activity in patients with pSS and mice with experimental Sjögren’s syndrome(ESS).Moreover,we detected high expression of IL-10 receptor on Tfh cells and their precursors in both humans and mice.In culture,IL-10 suppressed human and murine Tfh cell differentiation by promoting STAT5 phosphorylation.By using an adoptive transfer approach and two-photon live imaging,we found significantly increased numbers of Tfh cells with enhanced T cell homing into B cell follicles in the draining cervical lymph nodes of RAG-2−/−mice transferred with IL-10-deficient B cells during ESS development compared with those of RAG-2−/−mice transferred with wild-type B cells.In ESS mice,CD19^(+)CD1d^(hi)CD5^(+)Breg cells with decreased IL-10 production exhibited severely impaired suppressive effects on T cell proliferation.Consistently,CD19^(+)CD24^(+)CD38^(hi) Breg cells from pSS patients showed significantly reduced IL-10 production with defective inhibitory function in the suppression of autologous Tfh cell expansion.Furthermore,the adoptive transfer of IL-10-producing Breg cells markedly suppressed the Tfh cell response and ameliorated ESS progression in ESS mice.Together,these findings demonstrate a critical role for IL-10-producing Breg cells in restraining the effector Tfh cell response during pSS development.
基金Grants La Marató de TV3(071810)Fondo de Investigaciones Sanitarias(080103/1201009)"Ajut per a la Recerca Josep Font" from Hospital Clinic-Barcelona(PBZ,2012)
文摘Liver involvement was one of the first extraglandular manifestations to be reported in patients with primary Sj(o)gren syndrome (SS).In the 1990s,a study of liver involvement in patients with primary SS integrated the evaluation of clinical signs of liver disease,liver function and a complete panel of autoantibodies.Recent developments in the field of hepatic and viral diseases have significantly changed the diagnostic approach to liver involvement in SS.The most recent studies have shown that,after eliminating hepatotoxic drugs and fatty liver disease,the two main causes of liver disease in primary SS are chronic viral infections and autoimmune liver diseases.The differential diagnosis of liver disease in primary SS (viral vs autoimmune) is clinically important,since the two processes require different therapeutic approaches and have different prognoses.With respect to viral infections,chronic HCV infection is the main cause of liver involvement in SS patients from the Mediterranean area,while chronic HBV infection may be the main cause of liver involvement in SS patients from Asian countries.After eliminating viral hepatitis,primary biliary cirrhosis (PBC) should be considered the main cause of liver disease in primary SS.PBC-related SS patients may have a broad spectrum of abnormalities of the liver,including having no clinical or analytical data suggestive of liver disease.Autoimmune hepatitis (AIH) is the second most frequently found autoimmune liver disease to be associated with SS (all reported cases are type I),and nearly 10% of these patients have an AIH-PBC overlap.Finally,IgG4-related disease must be investigated in patients with SS presenting with sclerosing cholangitis,especially when autoimmune pancreatitis or retroperitoneal fibrosis are also present.