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
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
Introduction: Glomerular damage during Gougerot-Sjgren syndrome is much rarer than interstitial damage, and is essentially extra-membranous and membrano-proliferative glomerulonephritis. Observation: We report the cas...Introduction: Glomerular damage during Gougerot-Sjgren syndrome is much rarer than interstitial damage, and is essentially extra-membranous and membrano-proliferative glomerulonephritis. Observation: We report the case of a 44-year-old woman with primary Sjgrens syndrome, confirmed by clinical dryness syndrome, positive anti-SSA and anti-SSB antibodies, and a salivary gland biopsy revealing grade 4 lymphocytic sialadenitis according to CHISHOLMs classification. Later, the patient developed nephrotic syndrome, along with hypertension. Renal function remained normal with a creatinine level of 9.3 mg/l, and hematuria was absent. Only antinuclear antibodies tested positive, while anti-PLA2R antibodies were negative. A renal biopsy was performed, which was complicated on the same day by hemodynamic instability with hematuria. Renal CT scan with contrast injection revealed a posterior perirenal hematoma without contrast extravasation. Additionally, bilateral renal vein thrombosis was incidentally discovered, suggesting extramembranous glomerulonephritis. The patients hemodynamic status stabilized after fluid resuscitation with isotonic saline solution (0.9%), without the need for blood transfusion. Renal biopsy confirmed extramembranous glomerulonephritis with interstitial fibrosis and minimal tubular atrophy. The initial etiological assessment was negative. The patient was started on oral corticosteroids, angiotensin-converting enzyme inhibitors, and therapeutic anticoagulation for renal vein thrombosis. The patients condition improved, with the disappearance of the syndrome and spontaneous regression of the hematoma. Discussion: The association of nephrotic syndrome and renal vein thrombosis primarily suggests glomerulopathy, in particular extra-membranous glomerulonephritis. Sjgrens syndrome can be associated with extra-membranous glomerulonephritis without being its direct cause. Like, it is possible that it is a cause of glomerulonephritis, essentially extra membranous and membrano-proliferative. Conclusion: Sjgrens syndrome is generally underestimated cause of glomerulonephritis, which should be considered in cases of extra-membranous glomerulonephritis.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
<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
BACKGROUND Although the presentations of Sjögren’s syndrome(SS)are variable,ranging from mild dryness to wider systemic involvement,ranulas as early clinical signs were scarcely reported.Here,we present an adult...BACKGROUND Although the presentations of Sjögren’s syndrome(SS)are variable,ranging from mild dryness to wider systemic involvement,ranulas as early clinical signs were scarcely reported.Here,we present an adult patient with SS,who developed a unilateral simple ranula and was diagnosed primary SS 3 years later.We also provide a review of cases of SS and ranulas from 1980 to 2020.CASE SUMMARY A 22-year-old girl was found to have a left painless floor-of-mouth lesion 3 years ago,without obvious trauma or inducement.The diagnosis of a unilateral(left)simple ranula was made,and the ranula was surgically treated.Within 3 years after the ranula surgery,she developed acute lymphadenectasis in unilateral parotid twice without inducement,and ultrasonic examination revealed diffuse lesions in bilateral parotids and submandibular glands,which strongly suggested SS.Serologic tests and the unstimulated whole saliva flow rate confirmed the SS diagnosis.CONCLUSION Our study underlines that ranulas are early clinical signs of SS.As early diagnosis and early intervention of SS are important to obtain better outcomes,our findings underline the need for histopathological test after sublingual adenectomy and imaging detection of exocrine glands for the patients with ranulas.展开更多
Introduction: Sjögren’s syndrome is an autoimmune epithelitis with various extraglandular signs, among which are neurological, with a variable frequency according to studies. We report three cases of periphe...Introduction: Sjögren’s syndrome is an autoimmune epithelitis with various extraglandular signs, among which are neurological, with a variable frequency according to studies. We report three cases of peripheral neuropathy revealing Gougerot-Sjögren’s syndrome, collected in the Neurology Department of the Fann University Hospital in Dakar (Senegal). Observations: The first patient, aged 48 years, presented with a length-dependent sensitivomotor polyneuropathy associated with retrobulbar optic neuritis, with dry eyes and dry mouth noticed by the patient for several years. The second patient, aged 28 years, was admitted to the hospital with chronic generalized paresthesia in the context of xerostomia and xerophthalmia. The results of the clinical examination and the electroeneuromyogram were in favour of pure sensory neuronopathy. The third patient was 32 years old female, with a history of thyroidectomy and acute inflammatory demyelinating polyneuropathy (AIDP), who was seen for acute ascending flaccid tetraplegia with facial diplegia, preceded by diffuse paresthesia. The diagnosis of recurrence of acute demyelinating polyradiculonueropathy was retained in view of the rapidly increasing character of the deficit, the hyperproteinorachy at the lumbar puncture, and the signs of demyelination at the ENMG. The diagnosis of Gougerot-Sjögren’s syndrome in our three patients was established on the basis of the 2016 ACR/EULAR criteria. Indeed, the anti-SSA antibodies (Ro) were positive in our 3 patients with a biopsy of the salivary glands which showed stage 3 in the first patient and stage 4 in the two others. Corticosteroid therapy and immunosuppressive treatment resulted in a favourable clinical evolution on the neurological and general levels. Conclusion: Gougerot-Sjögren’s syndrome is an autoimmune exocrinopathy that may present with peripheral neuropathy, which may precede the diagnosis of Sjögren’s syndrome, be concomitant or occur during the course of the disease.展开更多
Introduction: Primary Sjögren’s syndrome (SS) is the most common connective tissue disease after rheumatoid arthritis and affects mostly women between 30 and 40 years of age with an estimated prevalence between ...Introduction: Primary Sjögren’s syndrome (SS) is the most common connective tissue disease after rheumatoid arthritis and affects mostly women between 30 and 40 years of age with an estimated prevalence between 0.1% and 0.6%. This observation illustrates an incidental finding of a case of SS in a young female patient in a context of obstructive renal failure (ARF) due to uterine fibroids. Observation: This was a 31-year-old woman hospitalized for anuric AKI (Acute Kidney Injury) with a creatinine level of 1247 μmol/l. Her history included sickle cell disease A/C and an unoperated uterine fibroid diagnosed 3 years ago. Approximately 2 months before her admission, her symptomatology was made of dizziness, physical asthenia, vomiting, poly-arthralgia, morning rash, pollakiuria and oral dryness. Abdominal examination showed a painless transverse mass in the pelvis. Biological examination showed a CRP (C-reactive protein) level of 488 mg/l. The cytobacteriological examination of the urine was normal and the proteinuria was 1.35 g/24 hours. The CT scan showed kidneys measuring 110 mm on the right and 113 mm on the left associated with bilateral pyelo-caliceal dilatation on a large polymyomatous uterus of interstitial and submucosal type. Immunologically, the anti-nuclear factor, the rheumatoid factor and the anti-SSA antibodies were positive. The resumption of the interrogation within the framework of the research of the subjective dry syndrome to find a notion of intermittent xerophthalmia 4 months ago. The Schirmer test was positive in the left eye. The initial management consisted of a polymyomectomy after 3 sessions of hemodialysis. Background treatment combining prednisone 5 mg/day and methotrexate 20 mg/week was started in parallel with the use of artificial tears. The evolution after twelve (12) months of treatment was favorable with a complete disappearance of the signs dry syndrome and full recovery of renal function. Conclusion: SS can have an insidious evolution and remain stable for many years, hence its fortuitous discovery in this case of obstructive ARF on uterine fibroid. In this context we insist on the interest of the immunological assessment in a patient in period of genital activity with a significant proteinuria and non-specific extrarenal signs.展开更多
Background:Sjögren’s syndrome(SS)is an autoimmune disorder characterized by sicca syndrome and/or systemic manifestations.The treatment is still challenging.This study aimed to explore the therapeutic role and m...Background:Sjögren’s syndrome(SS)is an autoimmune disorder characterized by sicca syndrome and/or systemic manifestations.The treatment is still challenging.This study aimed to explore the therapeutic role and mechanism of exosomes obtained from the supernatant of stem cells derived from human exfoliated deciduous teeth(SHED-exos)in sialadenitis caused by SS.Methods:SHED-exos were administered to the submandibular glands(SMGs)of 14-week-old non-obese diabetic(NOD)mice,an animal model of the clinical phase of SS,by local injection or intraductal infusion.The saliva flow rate was measured after pilocarpine intraperitoneal injection in 21-week-old NOD mice.Protein expression was examined by western blot analysis.Exosomal microRNA(miRNAs)were identified by microarray analysis.Paracellular permeability was evaluated by transepithelial electrical resistance measurement.Results:SHED-exos were injected into the SMG of NOD mice and increased saliva secretion.The injected SHED-exos were taken up by glandular epithelial cells,and further increased paracellular permeability mediated by zonula occluden-1(ZO-1).A total of 180 exosomal miRNAs were identified from SHED-exos,and Kyoto Encyclopedia of Genes and Genomes analysis suggested that the phosphatidylinositol 3 kinase(PI3K)/protein kinase B(Akt)pathway might play an important role.SHED-exos treatment down-regulated phospho-Akt(p-Akt)/Akt,phospho-glycogen synthase kinase 3b(p-GSK-3b)/GSK-3b,and Slug expressions and up-regulated ZO-1 expression in SMGs and SMG-C6 cells.Both the increased ZO-1 expression and paracellular permeability induced by SHED-exos were abolished by insulin-like growth factor 1,a PI3K agonist.Slug bound to the ZO-1 promoter and suppressed its expression.For safer and more effective clinical application,SHED-exos were intraductally infused into the SMGs of NOD mice,and saliva secretion was increased and accompanied by decreased levels of p-Akt/Akt,p-GSK-3b/GSK-3b,and Slug and increased ZO-1 expression.Conclusion:Local application of SHED-exos in SMGs can ameliorate Sjögren syndrome-induced hyposalivation by increasing the paracellular permeability of glandular epithelial cells through Akt/GSK-3b/Slug pathway-mediated ZO-1 expression.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
Mucosa-associated lymphoid tissue （MALT） lymphoma of the thymus is rare. We reported a case of a 37-year-old Chinese female with Sjtgren＇s syndrome and hyperglobulinemia. She suffered from chronic cough for 3 weeks...Mucosa-associated lymphoid tissue （MALT） lymphoma of the thymus is rare. We reported a case of a 37-year-old Chinese female with Sjtgren＇s syndrome and hyperglobulinemia. She suffered from chronic cough for 3 weeks. Chest computed tomography （CT） demonstrated a multiloculated cystic mass in mediastinum prevascular space and multiple lung cysts. Laboratory exam of autoimmune markers showed positive of antinuclear antibody （ANA）, Sjtgren＇s syndrome A （SSA）, Sjtgren＇s syndrome B （SSB）, and rheumatoid factors （RF）. Thymectomy with lymph node dissection was performed. The pathology report revealed thymic extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue. Under immunohistochemical stains, CD20 and Bcl-2 were positive. No evidence of recurrence of disease was found.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
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
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.
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.
文摘Introduction: Glomerular damage during Gougerot-Sjgren syndrome is much rarer than interstitial damage, and is essentially extra-membranous and membrano-proliferative glomerulonephritis. Observation: We report the case of a 44-year-old woman with primary Sjgrens syndrome, confirmed by clinical dryness syndrome, positive anti-SSA and anti-SSB antibodies, and a salivary gland biopsy revealing grade 4 lymphocytic sialadenitis according to CHISHOLMs classification. Later, the patient developed nephrotic syndrome, along with hypertension. Renal function remained normal with a creatinine level of 9.3 mg/l, and hematuria was absent. Only antinuclear antibodies tested positive, while anti-PLA2R antibodies were negative. A renal biopsy was performed, which was complicated on the same day by hemodynamic instability with hematuria. Renal CT scan with contrast injection revealed a posterior perirenal hematoma without contrast extravasation. Additionally, bilateral renal vein thrombosis was incidentally discovered, suggesting extramembranous glomerulonephritis. The patients hemodynamic status stabilized after fluid resuscitation with isotonic saline solution (0.9%), without the need for blood transfusion. Renal biopsy confirmed extramembranous glomerulonephritis with interstitial fibrosis and minimal tubular atrophy. The initial etiological assessment was negative. The patient was started on oral corticosteroids, angiotensin-converting enzyme inhibitors, and therapeutic anticoagulation for renal vein thrombosis. The patients condition improved, with the disappearance of the syndrome and spontaneous regression of the hematoma. Discussion: The association of nephrotic syndrome and renal vein thrombosis primarily suggests glomerulopathy, in particular extra-membranous glomerulonephritis. Sjgrens syndrome can be associated with extra-membranous glomerulonephritis without being its direct cause. Like, it is possible that it is a cause of glomerulonephritis, essentially extra membranous and membrano-proliferative. Conclusion: Sjgrens syndrome is generally underestimated cause of glomerulonephritis, which should be considered in cases of extra-membranous glomerulonephritis.
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.
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 the National Natural Science Foundation of China,No.81801600。
文摘BACKGROUND Although the presentations of Sjögren’s syndrome(SS)are variable,ranging from mild dryness to wider systemic involvement,ranulas as early clinical signs were scarcely reported.Here,we present an adult patient with SS,who developed a unilateral simple ranula and was diagnosed primary SS 3 years later.We also provide a review of cases of SS and ranulas from 1980 to 2020.CASE SUMMARY A 22-year-old girl was found to have a left painless floor-of-mouth lesion 3 years ago,without obvious trauma or inducement.The diagnosis of a unilateral(left)simple ranula was made,and the ranula was surgically treated.Within 3 years after the ranula surgery,she developed acute lymphadenectasis in unilateral parotid twice without inducement,and ultrasonic examination revealed diffuse lesions in bilateral parotids and submandibular glands,which strongly suggested SS.Serologic tests and the unstimulated whole saliva flow rate confirmed the SS diagnosis.CONCLUSION Our study underlines that ranulas are early clinical signs of SS.As early diagnosis and early intervention of SS are important to obtain better outcomes,our findings underline the need for histopathological test after sublingual adenectomy and imaging detection of exocrine glands for the patients with ranulas.
文摘Introduction: Sjögren’s syndrome is an autoimmune epithelitis with various extraglandular signs, among which are neurological, with a variable frequency according to studies. We report three cases of peripheral neuropathy revealing Gougerot-Sjögren’s syndrome, collected in the Neurology Department of the Fann University Hospital in Dakar (Senegal). Observations: The first patient, aged 48 years, presented with a length-dependent sensitivomotor polyneuropathy associated with retrobulbar optic neuritis, with dry eyes and dry mouth noticed by the patient for several years. The second patient, aged 28 years, was admitted to the hospital with chronic generalized paresthesia in the context of xerostomia and xerophthalmia. The results of the clinical examination and the electroeneuromyogram were in favour of pure sensory neuronopathy. The third patient was 32 years old female, with a history of thyroidectomy and acute inflammatory demyelinating polyneuropathy (AIDP), who was seen for acute ascending flaccid tetraplegia with facial diplegia, preceded by diffuse paresthesia. The diagnosis of recurrence of acute demyelinating polyradiculonueropathy was retained in view of the rapidly increasing character of the deficit, the hyperproteinorachy at the lumbar puncture, and the signs of demyelination at the ENMG. The diagnosis of Gougerot-Sjögren’s syndrome in our three patients was established on the basis of the 2016 ACR/EULAR criteria. Indeed, the anti-SSA antibodies (Ro) were positive in our 3 patients with a biopsy of the salivary glands which showed stage 3 in the first patient and stage 4 in the two others. Corticosteroid therapy and immunosuppressive treatment resulted in a favourable clinical evolution on the neurological and general levels. Conclusion: Gougerot-Sjögren’s syndrome is an autoimmune exocrinopathy that may present with peripheral neuropathy, which may precede the diagnosis of Sjögren’s syndrome, be concomitant or occur during the course of the disease.
文摘Introduction: Primary Sjögren’s syndrome (SS) is the most common connective tissue disease after rheumatoid arthritis and affects mostly women between 30 and 40 years of age with an estimated prevalence between 0.1% and 0.6%. This observation illustrates an incidental finding of a case of SS in a young female patient in a context of obstructive renal failure (ARF) due to uterine fibroids. Observation: This was a 31-year-old woman hospitalized for anuric AKI (Acute Kidney Injury) with a creatinine level of 1247 μmol/l. Her history included sickle cell disease A/C and an unoperated uterine fibroid diagnosed 3 years ago. Approximately 2 months before her admission, her symptomatology was made of dizziness, physical asthenia, vomiting, poly-arthralgia, morning rash, pollakiuria and oral dryness. Abdominal examination showed a painless transverse mass in the pelvis. Biological examination showed a CRP (C-reactive protein) level of 488 mg/l. The cytobacteriological examination of the urine was normal and the proteinuria was 1.35 g/24 hours. The CT scan showed kidneys measuring 110 mm on the right and 113 mm on the left associated with bilateral pyelo-caliceal dilatation on a large polymyomatous uterus of interstitial and submucosal type. Immunologically, the anti-nuclear factor, the rheumatoid factor and the anti-SSA antibodies were positive. The resumption of the interrogation within the framework of the research of the subjective dry syndrome to find a notion of intermittent xerophthalmia 4 months ago. The Schirmer test was positive in the left eye. The initial management consisted of a polymyomectomy after 3 sessions of hemodialysis. Background treatment combining prednisone 5 mg/day and methotrexate 20 mg/week was started in parallel with the use of artificial tears. The evolution after twelve (12) months of treatment was favorable with a complete disappearance of the signs dry syndrome and full recovery of renal function. Conclusion: SS can have an insidious evolution and remain stable for many years, hence its fortuitous discovery in this case of obstructive ARF on uterine fibroid. In this context we insist on the interest of the immunological assessment in a patient in period of genital activity with a significant proteinuria and non-specific extrarenal signs.
基金supported by grants from the National Natural Science Foundation of China(Nos.81974151 and 81771088)Peking University-Tason Stomatology Development Fund.
文摘Background:Sjögren’s syndrome(SS)is an autoimmune disorder characterized by sicca syndrome and/or systemic manifestations.The treatment is still challenging.This study aimed to explore the therapeutic role and mechanism of exosomes obtained from the supernatant of stem cells derived from human exfoliated deciduous teeth(SHED-exos)in sialadenitis caused by SS.Methods:SHED-exos were administered to the submandibular glands(SMGs)of 14-week-old non-obese diabetic(NOD)mice,an animal model of the clinical phase of SS,by local injection or intraductal infusion.The saliva flow rate was measured after pilocarpine intraperitoneal injection in 21-week-old NOD mice.Protein expression was examined by western blot analysis.Exosomal microRNA(miRNAs)were identified by microarray analysis.Paracellular permeability was evaluated by transepithelial electrical resistance measurement.Results:SHED-exos were injected into the SMG of NOD mice and increased saliva secretion.The injected SHED-exos were taken up by glandular epithelial cells,and further increased paracellular permeability mediated by zonula occluden-1(ZO-1).A total of 180 exosomal miRNAs were identified from SHED-exos,and Kyoto Encyclopedia of Genes and Genomes analysis suggested that the phosphatidylinositol 3 kinase(PI3K)/protein kinase B(Akt)pathway might play an important role.SHED-exos treatment down-regulated phospho-Akt(p-Akt)/Akt,phospho-glycogen synthase kinase 3b(p-GSK-3b)/GSK-3b,and Slug expressions and up-regulated ZO-1 expression in SMGs and SMG-C6 cells.Both the increased ZO-1 expression and paracellular permeability induced by SHED-exos were abolished by insulin-like growth factor 1,a PI3K agonist.Slug bound to the ZO-1 promoter and suppressed its expression.For safer and more effective clinical application,SHED-exos were intraductally infused into the SMGs of NOD mice,and saliva secretion was increased and accompanied by decreased levels of p-Akt/Akt,p-GSK-3b/GSK-3b,and Slug and increased ZO-1 expression.Conclusion:Local application of SHED-exos in SMGs can ameliorate Sjögren syndrome-induced hyposalivation by increasing the paracellular permeability of glandular epithelial cells through Akt/GSK-3b/Slug pathway-mediated ZO-1 expression.
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.
文摘Mucosa-associated lymphoid tissue （MALT） lymphoma of the thymus is rare. We reported a case of a 37-year-old Chinese female with Sjtgren＇s syndrome and hyperglobulinemia. She suffered from chronic cough for 3 weeks. Chest computed tomography （CT） demonstrated a multiloculated cystic mass in mediastinum prevascular space and multiple lung cysts. Laboratory exam of autoimmune markers showed positive of antinuclear antibody （ANA）, Sjtgren＇s syndrome A （SSA）, Sjtgren＇s syndrome B （SSB）, and rheumatoid factors （RF）. Thymectomy with lymph node dissection was performed. The pathology report revealed thymic extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue. Under immunohistochemical stains, CD20 and Bcl-2 were positive. No evidence of recurrence of disease was found.
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.
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.
文摘目的探讨原发性干燥综合征(primary Sj gren syndrome,pSS)患者唾液胱抑素D水平与唾液腺损伤的相关性。方法纳入2022年9月1日至2023年6月30日就诊于西安交通大学第一附属医院风湿免疫科pSS组患者51例及年龄、性别匹配的来院健康体检对照组人员51例。检测唾液中胱抑素D水平,采用独立样本t检验评估两组胱抑素D水平的差异,采用Pearson相关性检验评估pSS组胱抑素D与临床指标的关系。结果pSS组唾液中胱抑素D水平明显低于对照组(206.55±108.11 vs 374.32±172.24 pg/mL,P<0.01)。pSS患者胱抑素D水平与其静态唾液流率(r=0.433,P=0.002)及动态唾液流率(r=0.363,P=0.009)呈正相关。高唾液腺超声检查评分的pSS患者唾液胱抑素D水平明显低于低评分患者(腮腺:160.75±85.56 vs 290.53±95.17 pg/mL,P<0.01;颌下腺:157.76±87.59 vs 276.25±97.06 pg/mL,P<0.01)。pSS患者胱抑素D水平与外周血IL-6水平(r=-0.453,P=0.001)及CD4+T细胞计数(r=-0.396,P=0.005)呈负相关。结论pSS患者唾液胱抑素D水平可作为反映唾液腺损伤的指标。
