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Background: Primary Sjögren's syndrome (pSS) is a relatively common diffuse connective tissue disease that often invades exocrine glands, such as the lacrimal and salivary glands, and manifests as dry eyes and dry mouth. At present, the molecular mechanism of pSS is not clear. This study was designed to explore the internal mechanism of pSS from the gene level and screen out the immune-related diagnostic markers of pSS., Methods: The gene expression profiles GSE84844, GSE7451, and GSE40611 were downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were identified with R software. Then, the DEGs were intersected with the immune genes obtained from the ImmPort database to acquire differentially expressed immune-related genes (DEIRGs), and functional enrichment analyses were performed. The DEIRGs were screened through the least absolute shrinkage and selection operator (LASSO) logistic regression algorithm to obtain the optimal immune-related genes (IRGs). Expression levels of the optimal IRGs were verified by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) to obtain the key genes. Next, gene chips GSE7451 and GSE40611, from other tissues, were selected as the training sets to verify the sensitivity and specificity of the diagnosis of the key genes by receiver operating characteristic (ROC) analysis., Results: A total of 54 DEIRGs were obtained. The functional enrichment analysis results showed that they play an important role in immune and inflammatory responses. Nine optimal IRGs were screened from the DEIRGs by the LASSO logistic regression algorithm. After qRT-PCR verification, eight out of nine optimal IRGs ( IL-18, JAK2, TBK1, EED, TNFSF10, TNFSF13B, CYSLTR1 , and ICOS ) were significantly highly expressed in pSS patients and were defined as key genes. ROC analysis identified that TNFSF13B and CYSLTR1 had high sensitivity and specificity. Finally, the lack of previous research on EED and CYSLTR1 in pSS suggests that these IRGs may be regarded as new gateways to explore the diagnosis and pathogenesis of pSS., Conclusions: The key DEIRGs play a decisive role during the occurrence and development of pSS., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-1494/coif). The authors have no conflicts of interest to declare., (2022 Annals of Translational Medicine. All rights reserved.)

Background: Patients with thrombocytopenia accompanied by positive Ro/SS-A and/or La/SS-B autoantibodies have a possible diagnosis of Sjögren's syndrome (SS). Owing to its low prevalence, large-sample controlled studies on thrombocytopenia in primary SS (pSS) are scarce. Thus, this study aimed to investigate the clinical and laboratory characteristics of pSS complicated with mild to severe thrombocytopenia, and compared them with pSS patients without thrombocytopenia., Methods: This medical records review study analyzed the demographic data, clinical manifestations, laboratory examinations, and other results of 88 patients diagnosed with pSS between March 2007 and March 2018 in the Department of Rheumatology of The First Affiliated Hospital of Soochow University. A platelet (PLT) count of peripheral blood below 50×10 9 /L (≤50×10 9 /L) was regarded as mild to severe thrombocytopenia., Results: Of the 88 pSS patients, 43 developed mild to severe thrombocytopenia (thrombocytopenia group) and 45 had no thrombocytopenia (control group). No significant difference was found in the levels of autoantibodies and inflammatory markers between the thrombocytopenia group and the control group. Dry mouth (P<0.01) and dry eyes (P<0.01) were not frequently observed in the thrombocytopenia group, but the level of complement C4 dropped significantly (P<0.05). In contrast, the control group was more likely to have leukopenia (P=0.01) and interstitial lung disease (P<0.01)., Conclusions: In pSS patients with mild to severe thrombocytopenia, the incidence of xerostomia, xerophthalmia, and lung involvement was markedly reduced. Knowledge about the features of pSS associated with thrombocytopenia will lead to earlier and better diagnosis and treatment., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-162/coif). JW, XC and CL report this work was supported by grants from the National Natural Science Foundation of China (No. 81771782, No. 81801595, and No. 81873876). The other authors have no conflicts of interest to declare., (2022 Annals of Translational Medicine. All rights reserved.)

Background: Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease characterized by reduced exocrine gland (principally the salivary and lacrimal glands) activity caused by chronic lymphocytic infiltration. Although pSS has been closely associated with an increased risk of mucosa-associated lymphoid tissue (MALT) lymphoma, the dynamic epigenetic changes in the gland cells that accompany the pathogenesis are not entirely understood., Methods: In this study, we harvested tissue samples from the labial gland with (LG&#95;pSS) or without pSS (LG&#95;NC) before MALT development, as well as the parotid gland with tumor tissues (PG&#95;MALT) and paracancerous tissues (PG&#95;NC) of two pSS patients with MALT lymphoma, and conducted RNA-seq and ChIP-seq for tri-methylated histone 3 lysine 4, 9, 27, 36, and 79 (H3K4/9/27/36/79me3)., Results: Transcriptome landscapes indicated two outcomes of pSS progression with or without MALT lymphoma represented by distinct populations of differentially expressed genes and their functions. Furthermore, the epigenetic atlas of genome-wide H3K4/9/27/36/79me3 was in different stages for various samples, indicating that the variance of H3K4me3 was the earliest event, followed by selective alterations of H3K9/27/36/79me3. These four epigenetic modifications determine the final outcome of pSS progression., Conclusions: Our results not only advance the understanding of the dynamics of pSS progression and highlight the importance of epigenetic alterations in regulating transcription during this pathological process, but also identify potential therapeutic targets for pSS treatment and lymphoma intervention., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/atm-21-1754). The authors have no conflicts of interest to declare., (2021 Annals of Translational Medicine. All rights reserved.)