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Background: Primary Sjögren syndrome (pSjS) is one of the most prevalent systemic autoimmune diseases and characterized with hyperactivation of B cell and the abundant presence of autoantibodies in sera. The salivary gland epithelial cells (SGECs) release autoantigens to evoke autoimmunity through releasing elevated apoptosis or secreting autoantigen-containing exosomes, thus identifying autoantibodies directly to SGECs might provide insights into disease related biomarkers as well as further elucidating pathogenesis mechanisms. The present study was undertaken to identify autoantibodies to SGECs and to evaluate its clinical values in Chinese pSjS., Methods: Cell-based indirect immunofluorescence and immunostaining, two-dimensional electrophoresis and liquid chromatograph-tandem mass spectrometry were conducted to identify the autoantibodies to human salivary gland cell line A253 in pSjS sera. Enzyme-linked immunosorbent assay (ELISA) was applied to identify autoantibody titer in pSjS cohort and healthy controls. The prevalence and clinical significance of the identified autoantibodies was further assessed in pSjS population., Results: Anti-calreticulin (CALR) antibody was identified as a new autoantibody directly to SGECs in sera from pSjS patients. Anti-CALR antibody were detected in 37 of 120 pSjS patients (30.83 %) and 1 of 54 healthy controls (1.85 %). It was found in 40.85 % pSjS with anti-SSA positive, 53.85 % with anti-SSB positive, and 14.7 % in sero-negative pSjS. Anti-CALR antibody was associated with clinical manifestations including weight loss(p = 0.045), vasculitis (p = 0.031), and laboratory parameters including erythrocyte sedimentation rate (ESR) (r = 0.056, p = 0.021), Krebs von den Lungen-6 (KL-6) (r = 0.121, p = 0.035), IgG (r = 0.097, p < 0.001), IgG2 (r = 0.142, p = 0.022), IgG3 (r = 0.287, p < 0.001), fibrinogen (r = 0.084, p = 0.016), D-Dimer (r = 0.086, p = 0.012) and fibrinogen degradation production (r = 0.150, p = 0.002). The expression of CALR in salivary glands was related to lymphocytes infiltration into salivary glands in pSjS patients (r = 0.7076, p = 0.0034)., Conclusion: To our knowledge, this was the first study to investigate the prevalence and clinical significance of anti-CALR antibody in Chinses pSjS patients. The present study identified an autoimmune antibody, anti-CALR antibody, as a good autoimmune biomarker for sero-negative pSjS., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Primary immune thrombocytopaenia (ITP) is highly heterogeneous. ANA-positive primary ITP may resemble the preclinical stage of connective tissue diseases (CTDs), but is still considered primary ITP due to a controversial CTD risk assessment in this group. The objective of this study was to clarify the risk of CTD in ANA-positive patients with primary ITP., Methods: We performed a retrospective cohort study and a meta-analysis. 586 patients with newly diagnosed primary ITP were followed up and Cox regression analyses were used to analyse the associations of ANA positivity and other immune parameters with CTD development., Results: The mean follow-up time was 37 (19-56) months. ANA was positive in 21.33% (125 of 586) of patients with primary ITP in our retrospective cohort, and the overall rate of ANA positivity in the meta-analysis was 17.06% (369 of 2163). The adjusted HR for CTD in ANA-positive primary ITP was 6.15 (95% CI 2.66 to 14.23, p<0.001). Five patients in the ANA-positive group developed SLE (5 of 125, 4.0%), significantly higher than in the ANA-negative group (0 of 461, 0%). A clinical model combining ANA, anti-Sjogren's syndrome A antibody and C3 was successfully developed to predict the risk of CTD in patients with primary ITP. Increased risk of CTD (risk ratio=12.43, 95% CI 7.91 to 19.55, p<0.00001), especially SLE (risk ratio=30.41, 95% CI 13.23 to 69.86, p<0.00001), among ANA-positive patients with primary ITP was confirmed by a meta-analysis of previous studies and the present study., Conclusions: The findings suggest that ANA-positive primary ITP is a clinical entity distinct from other primary ITPs and is associated with increased risk of developing CTDs, especially SLE., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background/objective: The neurological involvement associated with primary Sjögren's syndrome (pSS) can be life threatening. However, the specific characteristics of pSS-related neurological involvement remain obscure. This study aimed at determining the clinical characteristics of this neurological involvement in patients with pSS., Methods: The clinical data of 205 patients with pSS who were admitted to our department between January 2015 and June 2017 were studied. Characteristics and laboratory findings of pSS patients with neurological abnormalities were compared with pSS patients without., Results: Forty of the 205 patients with pSS exhibited neurological abnormalities (19.51%); of these, 13 patients exhibited central nervous system (CNS) involvement only, 20 patients exhibited peripheral nervous system (PNS) involvement only, and 7 patients exhibited both, yielding a total of 20 (9.76%) patients with CNS involvement and 27 (13.17%) patients with PNS involvement. The titers of anti-Sjögren's syndrome type A (SSA) antibodies were significant higher while the presence of anti-Sjögren's syndrome type B (SSB) antibodies was significant lower in patients with vs. without neurological involvement. Similar results were found in patients with CNS involvement. No significant differences between patients with and without neurological involvement were found for the other clinical parameters examined., Conclusions: Neurological involvement in patients with pSS is common and needs to be carefully evaluated. Patients with pSS with a high titer of anti-SSA and low presence of anti-SSB antibodies might have a relatively high risk of developing neurological involvement. Future studies should focus on identifying biomarkers that may aid in the early diagnosis of neurological involvement in patients with pSS., Competing Interests: The authors declare that they have no conflict of interests., (Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc.)

Primary Sjögren's syndrome (pSS) is a rheumatic disease characterized by the destruction of salivary and lacrimal glands, and its pathogenesis mechanism remains unclear. G α q is the α -subunit of the heterotrimeric Gq protein. Researches demonstrated that G α q was involved in the pathogenesis regulation of several rheumatic diseases. This study explored the role of G α q in pSS. G α q mRNA levels in peripheral blood mononuclear cells (PBMCs) from 39 patients and 26 healthy controls (HCs) were investigated using real-time PCR. IL-17A serum concentrations in 22 pSS patients and 23 HCs were tested by ELISA, and the clinical significance of G α q was analyzed. The association of G α q with interleukin-17A (IL-17A) expression was also analyzed in patients with pSS. We showed that G α q expression in PBMCs from patients with pSS was significantly lower than that in PBMCs from HCs. G α q expression level was closely associated with pSS disease activity. Furthermore, a negative association was also found in IL-17A and G α q expression level. These data suggest that G α q is involved in pSS pathogenesis regulation, possibly due to its regulation of Th17. These results provide new insights into the pSS pathogenesis mechanism involving abnormal Th17 regulation.

In order to evaluate autoantibody to SP-1 as an early biomarker in pSS, we investigated autoantibody to SP-1 in Chinese patients with primary Sjögren's syndrome (pSS). Autoantibodies to SP-1 are significantly increased in pSS patients compared to RA patients, SLE patients, and healthy people without secondary SS. The presence of anti SP-1 antibodies was negatively correlated with the focus score (FS), RF, and salivary gland function. It was positively correlated with FS=0, RF≤20, and normal salivary gland function. In further studies, the autoantigen SP-1 was identified in ductal epithelia of salivary glands in il14α TG mice by IIF. SP-1 mRNAs expression increased with growing age in il14α TG mice. SP-1 mRNA was also identified in labial biopsies of patients with pSS. In conclusion, autoantibody to SP-1 is an early marker in pSS. It is useful to diagnose pSS patients who lack RF or antibodies to Ro/La., (Copyright © 2017. Published by Elsevier Inc.)

Fas and its ligand FasL, members of tumor necrosis factor receptor superfamily, have been implicated in the process of cell apoptosis. FasL consists of two forms, membrane FasL (mFasL) and soluble FasL (sFasL). sFasL can be produced by mFasL cleaved by matrix metalloproteinases (MMP) and also reveals a role for binding to Fas which is expressed on cell surface. Although Fas/FasL axis has been implicated in a variety of diseases, its role in Sjogren's syndrome still remains ill defined. In this study, we investigated the potential of sFasL in the pathogenesis of Sjogren's syndrome (SS). We found that the serum levels of sFasL in SS patients were significantly lower than healthy subjects. Moreover, serum levels of sFasL in patients with mild disease activity were higher than patients with severe disease activity. There is a positive correlation of the serum level of sFasL with uptake index of parotid gland in our expectation. In addition, liver injury involvement in SS patients showed decreased level of sFasL. Furthermore, we here also observed that the protective cytokine IL-10 expression was positively correlated with sFasL expression. Thus, our results here suggest a potential of sFasL in maintaining gland organ homeostasis., Competing Interests: The authors declare no conflict of interests regarding the publication of this paper.

To clarify clinical characteristics of immune thrombocytopenia (ITP) subsets associated with autoimmune diseases (AIDs).Five thousand five hundred twenty patients were reviewed retrospectively. One hundred four ITP patients were included for analysis. Clinical manifestations at first thrombocytopenic episode were recorded.Systemic lupus erythematosus (SLE) and primary Sjogren syndrome (pSS) accounted for a large part in AIDs associated with secondary ITP. SLE-ITP, pSS-ITP, and primary ITP (pITP) patients were different in several aspects in clinical and immunological characteristics. A subgroup of patients in pITP patients with some obvious autoimmune features (defined as AIF-ITP) such as positive ANA but failing to meet the diagnosis criteria now used for a specific kind of connective tissue diseases were also different with other pITP patients in some immunological features, indicating the difference in the pathogenesis mechanism of those autoimmune featured ITP patients.ITP patients were heterogeneous in clinical characteristics. Further study about the different pathogenesis of ITP subsets especially those AIF-ITP patients who only presented with thrombocytopenia will help us have a better understanding of pathogenesis of ITP and a better management of ITP patients., Competing Interests: The authors have no conflicts of interest to disclose.

Primary Sjögren's syndrome (pSS) is a rheumatic disease characterized by the destruction of salivary and lacrimal glands, and its pathogenesis mechanism remains unclear. Gαq is the α-subunit of the heterotrimeric Gq protein. Researches demonstrated that Gαq was involved in the pathogenesis regulation of several rheumatic diseases. This study explored the role of Gαq in pSS. Gαq mRNA levels in peripheral blood mononuclear cells (PBMCs) from 39 patients and 26 healthy controls (HCs) were investigated using real-time PCR. IL-17A serum concentrations in 22 pSS patients and 23 HCs were tested by ELISA, and the clinical significance of Gαq was analyzed. The association of Gαq with interleukin-17A (IL-17A) expression was also analyzed in patients with pSS. We showed that Gαq expression in PBMCs from patients with pSS was significantly lower than that in PBMCs from HCs. Gαq expression level was closely associated with pSS disease activity. Furthermore, a negative association was also found in IL-17A and Gαq expression level. These data suggest that Gαq is involved in pSS pathogenesis regulation, possibly due to its regulation of Th17. These results provide new insights into the pSS pathogenesis mechanism involving abnormal Th17 regulation. [ABSTRACT FROM AUTHOR]