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Objective: To investigate whether primary Sjögren's syndrome (pSS) patients with hyperglobulinemia have an increased risk of all-cause mortality., Methods: Patients who registered in the Chinese Rheumatism Data Centre from May 2016 to July 2021 and met the 2002 American European Consensus Group criteria or 2016 American College of Rheumatology /European League Against Rheumatism classification criteria for Sjögren's syndrome were included. Hyperglobulinemia was defined as any elevated serum levels of immunoglobulin G (IgG), immunoglobulin A (IgA), or immunoglobulin M (IgM). The primary outcome was all-cause death. Data for demographic and clinical characteristics, laboratory results, disease activity, damage scores, and treatments were evaluated., Results: A total of 9527 pSS patients were included in the analysis, of whom 4236 (44.5%) had at least one kind of elevated immunoglobulin level among IgG, IgA, and IgM. Patients with hyperglobulinemia had a significantly increased risk of death (crude hazard ratio 2.60; 95% confidence interval 1.91-3.55; adjusted hazard ratio 1.90; 95% confidence interval 1.20-3.01). The risk of death was positively correlated with IgG level (P trend <.001). The 5-, 10-, and 15-year survival rates of patients with hyperglobulinemia were 96.9%, 92.3%, and 87.9%, respectively, and significantly lower than the corresponding rates of 98.8%, 97.9%, and 96.4% in patients without hyperglobulinemia., Conclusions: Hyperglobulinemia is an independent risk factor for increased all-cause mortality in pSS patients. The risk of death is positively correlated with IgG level., (© Japan College of Rheumatology 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: To investigate the clinical features and factors associated with primary Sjögren's syndrome (pSS)-associated renal tubular acidosis (RTA)., Method: This case-control study was based on a multicenter pSS registry established by the Chinese Rheumatism Data Center. Patients with pSS, including those with RTA and those without renal involvement, between May 2016 and March 2020 were included in the analysis. Demographic, clinical, and laboratory data were also collected. Univariate and multivariate logistic regression analyses were used to identify factors that were associated with pSS-RTA., Results: This study included 257 pSS patients with RTA and 4222 patients without renal involvement. Significantly younger age at disease onset (40.1 ± 14.1 vs. 46.2 ± 13.1 years, P < 0.001), longer diagnosis interval (15.0 interquartile range [IQR] [1.0, 48.0] vs. 6.0 IQR [0, 34.0] months, P < 0.001), higher EULAR Sjögren's syndrome disease activity index (9 IQR [5, 15] vs. 3 IQR [0, 8], P < 0.001), and a higher prevalence of decreased estimated glomerular filtration rate (25.0% vs. 6.6%, P < 0.001) were observed in pSS patients with RTA than in those without renal involvement. Factors that were independently associated with pSS-RTA included age at disease onset ≤ 35 years (odds ratio [OR] 3.00, 95% confidence interval [CI] 2.27-3.97), thyroid disorders (OR 1.49, 95% CI 1.04-2.14), subjective dry mouth (OR 3.29, 95% CI 1.71-6.35), arthritis (OR 1.57, 95% CI 1.10-2.25), anti-SSB antibody positivity (OR 1.80, 95% CI 1.33-2.45), anemia (OR 1.67, 95% CI 1.26-2.21), elevated alkaline phosphatase level (OR 2.14, 95% CI 1.26-3.65), decreased albumin level (OR 1.61, 95% CI 1.00-2.60), and elevated erythrocyte sedimentation rate (OR 1.78, 95% CI 1.16-2.73)., Conclusions: Delayed diagnosis and decreased kidney function are common in pSS patients with RTA. pSS should be considered in patients with RTA, and early recognition and treatment may be useful in slowing the deterioration of renal function in patients with pSS-RTA. Key Points • pSS patients with RTA have earlier disease onset and higher disease activity than pSS patients without RTA, but the diagnosis was frequently delayed. • Decreased kidney function are common in pSS patients with RTA. • Sjögren's syndrome should be considered in young female patients with unexplained RTA, whereas RTA should be screened in pSS patients with early disease onset and elevated ALP level., (© 2022. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Introduction: Primary Sjögren's syndrome (pSS) has been related to a higher risk of comorbidities, but studies examining comorbidities among patients with and without extraglandular manifestations are limited. The objectives of this study were to assess the prevalence of comorbidities in Chinese pSS patients and to determine the relationship between comorbidities and extraglandular manifestations., Method: This cross-sectional study was based on the multicenter pSS registry established by the Chinese Rheumatism Data Center. Patients fulfilling the 2002 American-European criteria or the 2016 classification criteria for pSS were enrolled from May 2016 to December 2018. Demographic data, disease characteristics, comorbidities (cardiovascular disease, thyroid disorder, malignancy, and fragility fracture), and extraglandular manifestations were collected. Multivariate analyses were used to assess the relationships between comorbidities and extraglandular manifestations., Results: A total of 4087 pSS patients were included (95.7% female and mean age of 51.2 ± 13.1 years). The baseline prevalence of comorbidities was 3.8% for cardiovascular diseases, 12.1% for thyroid disorders, 1.8% for malignancies, and 1.7% for fragility fractures. The presence of extraglandular manifestations was associated with more comorbidities. Patients with more than one extraglandular manifestation had a higher prevalence of cardiovascular disease (adjusted odds ratio [aOR] 2.004, 95% confidence interval [CI] 1.221-3.288), thyroid disorder (aOR 1.380, 95% CI 1.022-1.863), and fragility fracture (aOR 2.684, 95% CI 1.505-4.786) after adjustment for age, sex, disease duration, and the significant variables in the univariate analysis., Conclusions: The presence of extraglandular manifestations in pSS was associated with an increased comorbidity burden, especially cardiovascular disease, thyroid disorder, and fragility fracture. Key Points • This is the first study assessing the association between extraglandular manifestations and comorbidity burden based on the largest pSS registry in China. • Patients with multiple extraglandular manifestations tend to have increased comorbid cardiovascular disease, thyroid disorder, and fragility fracture.

The muscarinic type 3 receptor (M3R) plays a pivotal role in the pathogenesis of Sjögren's syndrome (SS). Characterization of the crosstalk between M3R and EGFR has been investigated in some human malignancies. In the current study, we sought to investigate whether EGFR mimic immunization could alleviate the abnormal immune responses in an experimental SS-like model triggered by M3R peptides. After immunization with the combination of mimotope and M3R peptide, the active immunization targeting EGFR induced by the mimotope could reduce the marked infiltration of mononuclear cells, the high titer of antibodies against M3R and the accumulation of crucial pro-inflammatory cytokines in mice immunized with M3R peptide. Mechanistic analysis showed that mimotope immunization could alleviate the autoimmune response through inhibiting mitochondrion-mediated anti-apoptosis and up-regulating the FAS apoptosis pathway. These results may help to clarify the role of M3R in the pathogenesis of SS and suggested that transactivation of the EGFR signaling pathway may help M3R activate the autoimmune response in the pathogenesis of SS., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Primary Sjögren's syndrome is one of the most common autoimmune diseases. So far, genetic studies of Sjögren's syndrome have relied mostly on candidate gene approaches. To identify new genetic susceptibility loci for primary Sjögren's syndrome, we performed a three-stage genome-wide association study in Han Chinese. In the discovery stage, we analyzed 556,134 autosomal SNPs in 542 cases and 1,050 controls. We then validated promising associations in 2 replication stages comprising 1,303 cases and 2,727 controls. The combined analysis identified GTF2I at 7q11.23 (rs117026326: Pcombined = 1.31 × 10(-53), combined odds ratio (ORcombined) = 2.20) as a new susceptibility locus for primary Sjögren's syndrome. Our analysis also confirmed previously reported associations in Europeans in the regions of STAT4, TNFAIP3 and the major histocompatibility complex (MHC). Fine mapping of the region around GTF2I showed that rs117026326 in GTF2I had the most significant association, with associated SNPs extending from GTF2I to GTF2IRD1-GTF2I.

Objective: To investigate whether primary Sjögren's syndrome (pSS) patients with hyperglobulinemia have an increased risk of all-cause mortality. Methods: Patients who registered in the Chinese Rheumatism Data Centre from May 2016 to July 2021 and met the 2002 American European Consensus Group criteria or 2016 American College of Rheumatology /European League Against Rheumatism classification criteria for Sjögren's syndrome were included. Hyperglobulinemia was defined as any elevated serum levels of immunoglobulin G (IgG), immunoglobulin A (IgA), or immunoglobulin M (IgM). The primary outcome was all-cause death. Data for demographic and clinical characteristics, laboratory results, disease activity, damage scores, and treatments were evaluated. Results: A total of 9527 pSS patients were included in the analysis, of whom 4236 (44.5%) had at least one kind of elevated immunoglobulin level among IgG, IgA, and IgM. Patients with hyperglobulinemia had a significantly increased risk of death (crude hazard ratio 2.60; 95% confidence interval 1.91–3.55; adjusted hazard ratio 1.90; 95% confidence interval 1.20–3.01). The risk of death was positively correlated with IgG level (P trend <.001). The 5-, 10-, and 15-year survival rates of patients with hyperglobulinemia were 96.9%, 92.3%, and 87.9%, respectively, and significantly lower than the corresponding rates of 98.8%, 97.9%, and 96.4% in patients without hyperglobulinemia. Conclusions: Hyperglobulinemia is an independent risk factor for increased all-cause mortality in pSS patients. The risk of death is positively correlated with IgG level. [ABSTRACT FROM AUTHOR]