Primary Sj Gren Research Articles

MO142A SINGLE-CENTER CASE SERIES OF 150 PATIENTS WITH RENAL FANCONI SYNDROME

Abstract Background and Aims Renal Fanconi syndrome (RFS) is characterized by generalized dysfunctions of renal proximal tubular (PT) transport. The causes of FS can be inherited or acquired, the latter of which mostly includes drugs, heavy metals, monoclonal light chains (LC), and primary Sj gren’s syndrome (pSS). We intended to observe the clinico-pathological features of RFS with different etiologies. Method From January 2012 to September 2018, all the patients diagnosed as RFS in our hospital were enrolled. Their clinicopathological records were retrospectively reviewed. The diagnosis of RFS was defined as existence of ≥ 3 of the following five items alone or ≥ 2 items combined with an evidence of PT damages in kidney pathology: (I) normoglycemic glycosuria; (II) generalized aminoaciduria; (III) hypophosphatemia and hyperphosphaturia; (IV) hypouricemia and hyperuricosuria; (V) proximal RTA. Results: 1. Clinical characteristics We identified 150 RFS patients, with an average age of (45.9±14.2) years old and male: female ratio 1.3:1. They presented with different degrees of PT dysfunctions and the most common were hypophosphatemia (83.2%) and aminoaciduria (80.6%). Their mean eGFR levels were 76.3 (4.5-188.6) ml/min/1.73m2 with 73.5% had proteinuria. 2. Renal pathological features 47 RFS patients received kidney biopsy and the most common pathological diagnosis was interstitial nephritis. They all presented with different degrees of proximal tubule atrophy, defective brush border, interstitial edema and fibrosis. 3. Etiology-related clinicopathologic features The most common causes of our RFS were LC (14.0%), drugs (13.3%), and pSS (9.3%). Compared to pSS associated RFS, LC associated RFS patients showed a higher prevalence of bone involvement, more severe proteinuria and less severe hypokalemia (P < 0.05) despite similar eGFR levels. Specific renal pathological features were seen in different etiology groups, including crystalline formation and increased lysosomes in PT cells under electron microscope in LC associated RFS, and CD21 positive ectopic germinal center formation in renal interstitum in parts of the pSS associated RFS. Conclusion We identified 150 RFS with different etiologies and they showed etiology-specific patterns of PT dysfunctions and renal pathologic changes.

Case report on a 32-year-old female with elevated serum creatinine levels and primary Sjögren's syndrome-chronic interstitial nephritis.

Primary Sjögren's syndrome (PSS) is a chronic autoimmune disease characterized by lymphoplasmacytic infiltration of the exocrine glands, which results in multiple organs damage. Renal injury affects 0.3–27.0% of PSS patients, and tubulointerstitial nephritis is the most frequent form of nephropathy in PSS. The present study reports on the case of a 32-year-old female with a 1-year history of elevated serum creatinine levels, and a 6-month history of mild pain in the waist and leg. Blood biochemistry tests indicated a creatinine level of 221.3 µmol/l and estimated glomerular filtration rate of 24.6 ml/min/1.73 m2 [Chronic Kidney Disease Epidemiology (CKD-EPI) formula]. Accordingly, the patient was diagnosed with stage IV chronic kidney disease. To clarify the underlying cause of the disease, a kidney biopsy was performed, which revealed tubular epithelial cells with multiple focal and lamellar atrophy (~60%), as well as extensive renal interstitial fibrosis with scattered inflammatory cell infiltration. Based on these results, the patient was finally diagnosed with severe chronic interstitial nephritis, chronic kidney disease stage IV, PSS and anemia due to chronic kidney disease. The patient was treated with half-dose glucocorticoid (prednisone, 25 mg oral qd maintained up to 12 months). The patient's serum creatinine levels had decreased to 172.4 µmol/l after 1 month and to 178.7 µmol/l after 12 months. The present case concluded that young patients with chronic renal failure should first be assessed for rheumatic immune system diseases. PSS may involve several organs and the clinical manifestations may be varied. Although chronic renal failure is frequently the first manifestation of renal disorder due to PSS, it may be overlooked by clinicians. The present results suggest that further attention should be paid to determine the association between symptoms in the clinical setting.

Lung transplantation for connective tissue disease-associated interstitial lung disease recipient

Objective: To investigate the timing and complications of lung transplantation for the treatment of connective tissue disease-associated interstitial lung disease (CTD-ILD). Method: The clinical data of connective tissue-associated disease lung transplantation recipients from September, 2015 to February, 2017 were collected. Results: 11 patients with CTD-ILD were evaluated by lung transplantation and were treated with lung transplantation. Including 2 cases dermatomyositis/polymyositis and interstitial lung disease (PM/DM-ILD), 4 cases rheumatoid arthritis and interstitial lung disease (RA-ILD), 4 cases of primary Sjgren's syndrome and interstitial lung disease (pSS-ILD), 1 case of systemic sclerosis and interstitial lung disease (SSc-ILD). There are 6 cases are CTD-ILD-PAH patients of all. There were 5 males and 6 females, aged 37-70 years, with an average age of (52.73±9.53) years. 7 patients received single lung transplantation, 4 patients received double lung transplantation. 3 patients died in the early postoperative period, one for pulmonary embolism, one for septic shock and heart failure, one for severe primary graft failure (PGD). The remaining patients were followed up (4-24 months) with good survival, no acute and chronic rejection and other complications were observed. The survival rate was similar to that of other disease sources. Conclusion: There is no recurrence, acute and chronic rejection and other complications were observed in CTD-ILD and/or PAH lung transplant recipients. And the survival rate was comparable to that of other disease sources.Lung transplantation is a safe and effective choice for selected CTD-ILD patients.

Advances in the pathogenesis and treatment of primary Sj(o)gren's syndrome

Sj(o)gren's syndrome(SS)is a chronic autoimmune inflammatory disease characterized by predominant infiltration of lymphocytes in exocrine glands as well as presence of several autoantibodies in sera.Primary SS(pSS)is the condition in the absence of other definitively diagnosed autoimmune diseases.The pathogenesis of pSS remains unclear.Currently,pSS is considered to be induced by multiple environmental factors and endogenous antigens,which trigger a self-perpetuating inflammatory response in susceptible individuals,lead to abnormal cellular and humoral immunity followed by the impairment of exocrine glands,production of autoantibodies and damage to target organs.Although no ideal therapy is available,biological agents have offered new clues to the treatment of pSS. Key words: Sj(o)gren's syndrome; Diagnosis; Therapy

Analysis of thyroid functional abnormalities in primary Sj(o)gren's syndrome

Objective To explore the clinical characteristics of thyroid disease in patients with primary Sj(o)gren's syndrome (pSS).Methods A total of 81 pSS patients were retrospectively investigated for thyroid dysfunction and the presence of anti-thyroid peroxidase antibody (TPOAb),antithyroglobulin antibody (TGAb).Sex,age,erythrocyte sedimentation rate (ESR),C-reactive protein (CRP),white blood cell count,and serum immunoglobulins were also analyzed.Results Thirty-one patients were identified as having thyroid dysfunction,including 3 with hyperthyroidism,18 with hypothyroidism,and 10 with subclinical hypothyroidism.There were no significant differences in the incidences of some clinical manifestations between patients with or without thyroid dysfunction,such as dry mouth,dry eyes,joint pain,Raynaud's phenomenon,palpable purpura,peripheral neuropathy,interstitial lung disease,liver involvement,and renal tubular acidosis.Differences were not statistically significant for ESR and CRP between two groups.Also,the titers of anti-nuclear antibody,anti-SSA antibody,antiSSB antibodies,and rheumatoid factor between two groups showed no significant differences.However,white blood cell count [(5.65 ± 0.49 vs 7.22 ± 0.48) × 109/L,P＜0.05] and hematoglobin [(110.50 ± 3.64 vs 122.80 ± 3.02) g/L,P＜0.05],as well as the titers of TGAb [(587.30 ± 204.30 vs 58.76 ± 13.78) U/ml,P＜0.05] and TPOAb [(213.70 ± 39.64 vs 29.57 ± 8.49) IU/ml,P ＜ 0.05] were significantly different between the two groups.Conclusions Thyroid diseases are frequently associated with pSS.Therefore,extended screening for existing thyroid diseases during the routine assessment of pSS patients is recommended. Key words: Primary Sj(o)gren syndrome; Thyroid disease

A correlation study on depression and life events of patients with primary sjogren syndrome

Objective To explore the relationship between life events and depression of patients with primary sjgren's syndrome(PSS). Methods 80 patients with PSS complicating depressive disorder were tested by self-rating depression scale(SDS) and life event scale(LES), and compared with the control group including 80 PSS patients with non-depressive disorder matched with age and sex.Then the correlation between SDS and LES were analyzed. Results The total score of life events(32.72±13.93), the score of negative life events(24.36±11.24), the score of SDS(58.60±16.78) and the frequency of life events(91.3%) in the research group were higher than those in control group(P<0.05), but the positive life events score(7.15±5.84) was lower than that in control group(9.76±7.29), and there was statistically significant difference between the two groups (P<0.05), there were more negative life events, especially on the aspects of family, work and study in the research group.There was positive correlation among the negative life events score, total score of life events and SDS score in the research group(P<0.01), meanwhile, negative correlation was revealed between the score of positive life events and SDS score in the research group(P<0.05). Conclusion Patients with PSS complicating depressive disorder experienced more negative life events which play an important role in depression of patients with PSS. Key words: Primary sjgren’s syndrome; Depressive disorder; Life events

Analysis of B-cell activating factor (BAFF) gene polymorphisms (-2841 T/C, -2704 T/C, -2701 T/A, -871 C/T) and soluble BAFF levels in primary Sj�gren's syndrome

Analysis of B-cell activating factor (BAFF) gene polymorphisms (-2841 T/C, -2704 T/C, -2701 T/A, -871 C/T) and soluble BAFF levels in primary Sj�gren's syndrome

Interleukin-10 gene polymorphisms (-1082 A/G, -819 C/T, -592 C/A) in primary Sj�gren's syndrome

Event Abstract Back to Event Interleukin-10 gene polymorphisms (-1082 A/G, -819 C/T, -592 C/A) in primary Sjögren's syndrome Edith Oregon-Romero1*, Mirna Vázquez-Villamar1, Diana C. Salazar-Camarena1, Beatriz A. Treviño-Talavera1, Gerardo Orozco-Barocio2, José F. Muñoz-Valle1, Yeminia M. Valle-Delgadillo1 and Claudia A. Palafox-Sánchez1, 2 1 Universidad de Guadalajara, Mexico 2 Hospital General de Occidente, Servicio de Reumatología, Mexico Introduction: Primary Sjögren´s syndrome (pSS) is an autoimmune disease of unknown etiology affecting primarily salivary and lacrimal exocrine glands. It is characterized by a progressive lymphocytic infiltration where B cells produce a great variety of antibodies, including those against ribonucleoproteins Ro and La. IL-10 plays an important role in pSS by promoting the differentiation of B cells inducing antibody production. Three polymorphic sites located at positions -1082 (A/G), -819 (C/T) and -592 (C/A) in the IL-10 promoter show a linkage disequilibrium and form haplotypes that may influence the IL-10 production and consequently an increased activity of the disease. Objective: To determine the frequency of haplotypes in the IL-10 promoter gene in patients with pSS. Methodology: The study included 113 Mexican mestizo patients with pSS, classified according to the American-European Consensus criteria, from the Department of Rheumatology (Hospital General de Occidente, SSJ). As control group, 154 clinically healthy subjects were included. The polymorphisms were genotyped by PCR/RFLP technique. Statistical analysis was carried out with the Stata 9.0 and EmHapFre software. Results: Polymorphisms were in Hardy–Weinberg equilibrium (-1082 A/G p=0.8377, -819C/T p= 0.1174, -592 C/A p=0.7953) and showed high linkage disequilibrium (100%, pc=1.42 x 10-34).The most frequent haplotypes were: ACC (41-61%), ATT (21.38%), GTA (14.86%), and GCC (11.18%). GTC haplotype was associated with a 4.35-fold less probability to develop pSS [OR; 95%CI: 0.23 (0.064-0.792) p= 0.01]. Conclusion: Our results suggest that carriers of the GTC haplotype have a protective status for the development of pSS. Keywords: primary Sjögren´s syndrome, Antibodies, IL-10 promoter, Linkage Disequilibrium, Haplotypes Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Immune-mediated disease pathogenesis Citation: Oregon-Romero E, Vázquez-Villamar M, Salazar-Camarena DC, Treviño-Talavera BA, Orozco-Barocio G, Muñoz-Valle JF, Valle-Delgadillo YM and Palafox-Sánchez CA (2013). Interleukin-10 gene polymorphisms (-1082 A/G, -819 C/T, -592 C/A) in primary Sjögren's syndrome. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.00346 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 15 Mar 2013; Published Online: 22 Aug 2013. * Correspondence: Dr. Edith Oregon-Romero, Universidad de Guadalajara, Guadalajara, Mexico, oregon_edith@hotmail.com Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Edith Oregon-Romero Mirna Vázquez-Villamar Diana C Salazar-Camarena Beatriz A Treviño-Talavera Gerardo Orozco-Barocio José F Muñoz-Valle Yeminia M Valle-Delgadillo Claudia A Palafox-Sánchez Google Edith Oregon-Romero Mirna Vázquez-Villamar Diana C Salazar-Camarena Beatriz A Treviño-Talavera Gerardo Orozco-Barocio José F Muñoz-Valle Yeminia M Valle-Delgadillo Claudia A Palafox-Sánchez Google Scholar Edith Oregon-Romero Mirna Vázquez-Villamar Diana C Salazar-Camarena Beatriz A Treviño-Talavera Gerardo Orozco-Barocio José F Muñoz-Valle Yeminia M Valle-Delgadillo Claudia A Palafox-Sánchez PubMed Edith Oregon-Romero Mirna Vázquez-Villamar Diana C Salazar-Camarena Beatriz A Treviño-Talavera Gerardo Orozco-Barocio José F Muñoz-Valle Yeminia M Valle-Delgadillo Claudia A Palafox-Sánchez Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

BAFF, ? and ? free light chains, C4d and IgG in serum and relations with peripheral blood lymphocyte populations in patients with primary Sj�gren�s syndrome

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Distribution of peripheral blood lymphocyte populations in patients with primary Sj�gren�s syndrome

Event Abstract Back to Event Distribution of peripheral blood lymphocyte populations in patients with primary Sjögren’s syndrome Gintaras Sudzius1*, Dainius Characiejus1, Diana Mieliauskaite2, Almantas Siaurys1, Irena Butrimiene2 and Irena Dumalakiene1 1 State Research Institute Center for Innovative Medicine, Department of Immunology, Lithuania 2 State Research Institute Center for Innovative Medicine, Department of Innovative diagnostic treatment and health monitoring technology, Lithuania Distribution of lymphocyte populations’ in peripheral blood mononuclear cells (PBMCs) of patients with primary Sjögren's syndrome (pSS) without (1pSS) or with (2pSS) extraglandular manifestations were investigated. 30 1pSS, 23 2pSS and 35 healthy controls were enrolled in the study. PBMCs were stimulated in whole blood with PMA and ionomycin, PBMCs labelled for CD3, CD4, CD8, CD19, CD16+56, CD25, CD27, CD57, Foxp3 and IL-17A and analyzed by flow cytometry. Decline in CD3+ T cells in PBMCs of patients with pSS was detected. The reason for this was significantly decreased absolute counts of CD4+, CD8+ and CD3+CD16+56 cells in patients with pSS. Significant decrease in absolute counts of CD4+IL17A+ and CD8brightCD57-CD27+ cells in patients with pSS were observed as compared to control group. Absolute counts of CD4+25brightFoxp3 and CD19+ cells were similar in all three groups and CD3-CD16+56 cells was significantly decreased only in 1pSS group. All results between 1pSS and 2pSS groups were comparable. However, different correlations between lymphocyte populations in 1pSS and 2pSS groups were found. Only in 1pSS the correlation between CD3-CD16+56 and CD3+CD16+56, CD3-CD16+56 and CD4+25brightFoxp3, CD4+ and CD19+, CD4+ and CD8brightCD57-CD27+ cells was registered. Whereas, in 2pSS the correlation between CD4+ and CD4+IL-17A+, CD8+ and CD3+CD16+56, CD4+IL-17A+ and CD8brightCD57-CD27+ cells was revealed. Declining and variations of T-lymphocyte subsets in pSS patients` could be the result of increased apoptosis and/or migration to inflamed tissues of CD4+IL-17A+, CD8brightCD57-CD27+, CD3+CD16+56 and CD3-CD16+56 (only in 1pSS group) cells. We suppose that these cell populations play an important role in pSS pathogenesis. Acknowledgements This research was funded by a grant No. LIG-23/2010 from the Research Council of Lithuania. Keywords: primary Sjögren's syndrome, extraglandular manifestations, distribution of lymphocyte populations, PBMCs, lymphocitopenia Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Immune-mediated disease pathogenesis Citation: Sudzius G, Characiejus D, Mieliauskaite D, Siaurys A, Butrimiene I and Dumalakiene I (2013). Distribution of peripheral blood lymphocyte populations in patients with primary Sjögren’s syndrome. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.00226 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 14 Mar 2013; Published Online: 22 Aug 2013. * Correspondence: Mr. Gintaras Sudzius, State Research Institute Center for Innovative Medicine, Department of Immunology, Vilnius, Lithuania, gintaras.sudzius@gmail.com Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Gintaras Sudzius Dainius Characiejus Diana Mieliauskaite Almantas Siaurys Irena Butrimiene Irena Dumalakiene Google Gintaras Sudzius Dainius Characiejus Diana Mieliauskaite Almantas Siaurys Irena Butrimiene Irena Dumalakiene Google Scholar Gintaras Sudzius Dainius Characiejus Diana Mieliauskaite Almantas Siaurys Irena Butrimiene Irena Dumalakiene PubMed Gintaras Sudzius Dainius Characiejus Diana Mieliauskaite Almantas Siaurys Irena Butrimiene Irena Dumalakiene Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

TNF receptor-associated factor 6 expression in peripheral blood mononuclear cells of patients with primary Sjgren’s syndrome and its clinical significance

TNF receptor-associated factor 6 expression in peripheral blood mononuclear cells of patients with primary Sjgren’s syndrome and its clinical significance

Expression of B cell activating factor-receptor in the sera of patients with primary Sj(o)gren' s syndrome

Objective To determine the serum levels of B cell activating factor-receptor(BAFF-R)in patients with primary Sj(o)gren's syndrome(pSS)and investigate the role of BAFF-R in the pathogenesis of pSS.Methods The serum concentration of BAFF-R was measured by ELISA in 120 patients with pSS and 62 age-and sex-matched normal controls.Results The median level of serum BAFF-R was(692.7 ± 536.9)ng/L in pSS and (279.7 ± 186.9)ng/L in healthy controls.The serum level of BAFF-R in the pSS was significantly higher than normal controls(P ＜0.01).Higher level of BAFF-R was associated with higher level of IgG(r =0.429,P ＜0.01).Serum level of BAFF-R had no correlation with IgA,IgM,C3,C4,RF,ESR and CRP.BAFF-R level was markedly increased in patients with positive ANA,anti-SSA,anti-SSB antibody compared with those with negative antibody.Conclusion The serum BAFF-R level was significantly elevated and correlated with the level of immunoglobulin and autoantibodies.BAFF-R play certain role in the pathogenesis of pSS. Key words: Sj(o)gren's syndrome,primary; B cell activating factor; ELISA

Expression of proteasome immunosubunit in labial glands of patients with primary Sjogren's syndrome.

To investigate the expression of proteasome immunosubunit low molecular weight polypeptide (LMP)2 and LMP7 in labial glands of patients with primary Sjogren's syndrome patients, and thus explore their role in the diagnosis, differential diagnosis and pathogenesis of primary Sjogren's syndrome (pSS). Labial specimens were collected from 40 patients with pSS, 15 patients with connective tissue diseases other than pSS, and 9 healthy controls. The expressions of LMP2 and LMP7 in labial specimens were determined using immunohistochemical approaches and analyzed using semi-quantitative methods. The positive rate of acinar was calculated. After the square arcsine transformation of data, the differences of the positive rate in acinar between LMP2 and LMP7 were compared among three groups. Spearman's rank correlation coefficient was used for analyzing the correlation of clinical manifestations with LMP2 and LMP7 expressions. The expressions of LMP2 and LMP7 within the acinar and ductal epithelial cells were confirmed. Although the LMP2 expression in labial specimens was not significantly different among three groups(P=0.369), the expression of LMP7 was significantly higher in pSS patients compared with patients with connective tissue disease and healthy controls (P<0.01). Only in pSS group, LMP7 was found to be with higher positive rate in acinar than LMP2 (P<0.01). No significant correlation was found between LMP2/LMP7 and clinical manifestations (P>0.05). In patients with pSS, the expression of LMP7 (but not LMP2) is up-regulated in labial gland, indicating these two proteins have different genetic regulation mechanisms.

ögren syndrome complicated with liver damage and itsrelated factors

：Objective To studyclinical features of liver damage in primary Sj(o)gren syndrome (pSS) and its relatedfactors.Methods One hundred and forty-nine patients of confirmed pSS hospitalized atPeking University People's Hospital were analyzed retrospectively.Results Seventeen of 149patients of pSS (11.4%) showed liver damage,10 diagnosed as autoimmune hepatitis and sevenas primary biliary liver cirrhosis.Increased serum levels of IgG,IgM and γ-globulinaccounted for 88.2% and 50.8%,35.3% and 5.3%,and 94.1% and 47.7% of those complicated withand without liver damage,respectively,with statistically significant difference (P ＜ 0.05).Positive serum anti-mitochondria antibody subtype M2 (AMA-M2)was 35.3% in pSS patients with liver damage,significantly higher than that in thosewithout liver damage (1.5%) (P ＜ 0.05).Independent riskfactors significantly associated with liver damage included age (OR = 1.013,95% CI0.971-1.058),course of illness (OR = 1.089,95% CI 1.032-1.150),serum level of γ-globulin(OR = 4.021,95% CI 1.246-12.982),positive AMA-M2 (OR = 11.82,95% CI 0.005-0.157),andpositive anti-SSA (OR = 101.333,95% CI 12.653-811.560).Conclusions Liver damage occurredrather high in pSS patients and increased serum levels of IgG,IgM,γ-globulinand anti-SSA can be used to predict their complication with liver damage.Age,course ofillness,serum level of γ-globulin,positive AMA-M2 and positive anti-SSA are all significantly associatedwith liver damage in pSS patients. Key words: Sj(o)gren's syndrome; Hepatitis,autoimmune; Livercirrhosis,biliary

Myositis in primary Sj(o)gren's syndrome

This study was to identify the clinical features of myositis complicated with primary Sj(o)gren's syndrome (pSS). A total of 202 patients with pSS were investigated. Myositis was diagnosed according to the clinical findings, muscle enzyme levels, electromyographic results, and muscle biopsy, and compared with 15 polymyositis (PM) patients. Myositis was identified in 4 of 202 pSS patients (2.0%). They developed myositis 5 to 20 years after the onset of SS. Two patients showed no myalgia and muscular weakness. Creative kinase (CK) was increased from 480 to 2702 IU/L. Anti-Jo-1 antibody was negative. All patients responded well to prednisone and had a median serum CK decrease by 48.9%. No patients had myositis recurrence. Compared with the PM group, the percentage of myalgia, peak of CK, descending rate of CK, and positive rate of anti-Jo-1 antibody were all significantly different. Myositis with Sj(o)gren's syndrome is not common, show relatively moderate symptoms, and respond well to prednisone. Key words: Sj(o)gren's syndrome; Myositis

Myositis in primary Sj�gren's syndrome: clinical and pathological report

To clarify the clinical features of myositis complicated with primary Sjögren's syndrome (SS), we studied 89 patients with Sjögren's syndrome (one male and 88 females; mean age 56.0 ± 15.31 years). Myositis was diagnosed from clinical findings, muscle enzymes, electromyographic findings, and muscle biopsy findings. Myositis was diagnosed in 5 of 89 SS patients (5.6%). One patient developed myositis 7 months after the onset of SS. The other four patients were diagnosed with myositis and SS simultaneously. Muscular weakness was mild and slowly progressive over 4–14 months (mean 8.4 months). All patients were able to walk without any assistance at the start of prednisolone therapy. Muscular enzymes were slightly elevated (from 1.5- to 12-fold). All patients tested negative for anti-Jo1 antibody and tested positive for antinuclear antibody. Anti-Ro(SSA) antibody was positive in 4/5 (90%); anti-La(SSB) was positive in 2/5 (40%). Although the clinical features of all patients met the criteria for polymyositis of Bohan, they responded well to small or moderate doses of prednisolone, which could be decreased without a recurrence of muscular weakness in all patients. Myositis with Sjögren's syndrome showed relatively moderate symptoms and responded well to prednisolone. A prospective follow-up of patients may provide further information.

Detecting abnormal regional cerebral blood flow in patients with primary Sjögren's syndrome by technetium-99m ethyl cysteinate dimer single photon emission computed tomography of the brain--a preliminary report.

Technetium-99m ethyl cysteinate dimer (Tc-99m ECD) brain single photon emission computed tomography (SPECT) was used to detect abnormal regional cerebral blood flow (rCBF) in 32 female patients with primary Sjögren's syndrome (PSS) showing definite neuropsychiatric symptoms/signs and normal brain magnetic resonance imaging (MRI) findings. It demonstrated hypoperfusion brain lesions in 18 (56.3%) of the patients, most frequently in the parietal lobes, and appears to be a sensitive tool for this clinical application.

Genetic association between interleukin-10 promoter region polymorphisms and primary Sjögren's syndrome.

To determine whether the haplotypes formed on the basis of single-base-exchange polymorphisms at positions -1082, -819, or -592 of the interleukin-10 (IL-10) gene predispose subjects to primary Sjögren's syndrome (SS). The frequency of IL-10 polymorphisms was analyzed in 62 patients with primary SS and in 400 healthy subjects. These data were assessed for correlations with the concentration of IL-10 in the plasma. The frequency of the IL-10 GCC haplotype (G at position -1082, C at position -819, and C at position -592 of the IL-10 gene) was increased (P < 0.05, odds ratio [OR] 1.90, 95% confidence interval [95% CI] 0.955-3.62) and the frequency of the ACC haplotype decreased (P < 0.05, OR 0.443, 95% CI 0.257-0.764) in primary SS patients compared with healthy controls. Moreover, the frequency of the ATA haplotype was similar in primary SS patients and healthy controls, but the incidence of the GCC/ATA genotype was elevated in the primary SS patients (P < 0.05, OR 2.19, 95% CI 1.19-4.03). The concentration of plasma IL-10 was significantly higher in patients carrying the GCC haplotype than in non-carriers of GCC. These results suggest that the presence of the GCC haplotype or the GCC/ATA genotype and the absence of the ACC haplotype of the IL-10 gene are associated with an increased susceptibility to primary SS. This effect is probably mediated by the increased capability to produce IL-10 among carriers of the GCC haplotype.

Alteration of peripheral blood dendritic cells in patients with primary Sjögren's syndrome.

We recently identified 3 fractions of human peripheral blood (PB) dendritic cells (DC), including the monocyte-associated fractions 1 and 2 (CD1a+,CD11c+ and CD1a-,CD11c+, respectively) and the lymphoid-associated fraction 3 (CD1a-,CD11c-). We attempted to determine whether these fractions were altered in Sjögren's syndrome (SS). We examined 23 patients with primary SS and 22 normal control subjects. DC were purified from PB and analyzed by flow cytometry. Immunohistochemical staining of labial salivary glands of SS patients was performed with monoclonal antibodies against fascin, which is known to be specific for DC. The total numbers of PB DC and fraction 1 DC were decreased in SS. Immunohistochemical staining demonstrated that fascin+,CD11c+,HLA-DR+ mononuclear cells were present and scattered among numerous fascin-hyperfiltrating cells in SS patients. Interferon-gamma (IFNgamma)-producing Th1 cells were shown to be increased in both PB and salivary glands of patients, indicating the presence of general IFNgamma-producing Th1 polarization in SS. Furthermore, numbers of Thl cells were increased when naive T cells were cocultured with fraction 1 DC in vitro. These findings suggest selective trafficking of fraction 1 DC into focal sites of inflammation and subsequent promotion of Th1 balance, suggesting a novel pathogenesis of SS.

Polymorphisms of the Ro52 gene associated with anti-Ro 52-kd autoantibodies in patients with primary Sjögren's syndrome.

To screen for the Ro52 gene encoding the 52-kd Ro autoantigen for possible mutations and polymorphisms associated with primary Sjogren's syndrome (SS). The restriction enzyme fragment-single-strand conformation polymorphism method was used to search for mutations and polymorphisms in the Ro52 gene in 97 patients with primary SS and 72 healthy control subjects. The results were verified by automated DNA sequencing and natural or amplification-created restriction site tests. A single-nucleotide polymorphism (SNP) was discovered in intron 3 (137 bp upstream of exon 4). The C/T genotype was significantly more prevalent among patients who were positive for anti-Ro 52-kd (20 of 38) than among healthy controls (9 of 72) (P = 0.00003); significant differences were not seen in patients who were negative for anti-Ro 52-kd. Furthermore, the frequency of the T allele in this position among groups of anti-Ro 52-kd-positive patients, anti-Ro 52-kd-negative patients, and control subjects was significantly increased in the patients who were positive for anti-Ro 52-kd compared with the controls. We present the results of a complete screening for the Ro52 gene in patients with primary SS and the results of an association study. An SNP in intron 3 was found to be strongly associated with the presence of anti-Ro 52-kd autoantibodies in primary SS. This finding is interesting in light of the fact that an alternative messenger RNA is made by deleting exon 4, which encodes a putative leucine zipper domain, to generate a shorter version of the Ro 52-kd protein.