THU0242 REGULATORY ROLE OF TRANSCRIPTION FACTOR BLIMP-1 IN SJÖGREN’S SYNDROME
Authors: R. Wu, L. Wang, X. Zheng, Y. Wang, G. Wang, X. Li, X. Li
Journal: Annals of the Rheumatic Diseases (2020)

Background: The pathogenesis of primary sjögren’s syndrome (pSS) is multifactorial. Self-antigen-driven responses perform a vital function in the development of autoimmune diseases [1]. B cells, only 20-25% of total infiltrating cells in labial glands, are the cellular basis for spontaneous antibody production [2].Genome-wide association studies (GWAS) have identified Blimp-1 as a susceptibility gene for autoimmune diseases and played an important role in the pathogenesis of autoimmune diseases [3]. Objectives: To investigate the expression and effect of B lymphocyte induced maturation protein 1 (Blimp-1) in pSS and the correlation of Blimp-1 with B cell subsets and clinical features. Methods: The PRDM1 mRNA expression in B lymphocyte and labial gland were examined by RT-PCR. The levels of B cell subsets were examined by flow cytometry. Hematoxylin-eosin (HE) staining and immunohistochemistry (IHC) were used to examine the invasion degree of lymph cell and Blimp-1 distribution, respectively. The correlation of PRDM1 mRNA with B cell subsets and clinical indicators were also analyzed. Results: The levels of PRDM1 mRNA expression of B cells were significantly higher in SS than in healthy controls (HC) and which were also significantly higher in the high immunoglobulin (Ig) group than that in normal Ig group ( P &lt;0.02, Fig. 1a-b). The number of CD19+B cells and CD138+ plasma cells(PC) have increased while the CD27+ cells decreased in SS( P &lt;0.05). The percentage of PC and PC/B is positively correlated with PRDM1 mRNA( r =0.380, P =0.002; r =0.317, P =0.009, Fig. 1c-d). Blimp-1 expression level showed a positive correlation with invasion degree of lymph cell in histology (Fig. 2a-c), Ig levels and ESSDAI score and an inverse correlation with the glucocorticoids usage (Fig. 3c). Fig. 1 (a-b) RT-PCR showed that PRDM1 mRNA expression in SS patients and HC. (c-d) Correlation between PRDM1 mRNA expression and PC and PC/B. Fig. 2 (a) Expression of Blimp-1 in labial glands of sjögren’s syndrome. (b) PRDM1 mRNA levels in different invasion degree of lymph cell group. (c) Correlation between PRDM1 mRNA expression and invasion degree of lymph cell. *p&lt;0.05, ***p&lt;0.001. Fig. 3 (a-b) RT-PCR showed that PRDM1 mRNA expression in different usage of glucocorticoids. (c) Correlation between PRDM1 mRNA expression and different glucocorticoid usage. **p&lt;0.01, ***p&lt;0.001. Conclusion: Blimp-1 displayed high expression in SS, which could affect pSS disease activity. SS activity is suppressed by glucocorticoid which might be through inhibition of Blimp-1. References: [1]Kapsogeorgou EK, Abu-Helu RF, Moutsopoulos HM, Manoussakis MN (2005) Salivary gland epithelial cell exosomes: A source of autoantigenic ribonucleoproteins. Arthritis Rheum 52(5):1517-21. https://doi.org/10.1002/art.21005 [2]Arneth BM (2019) Impact of B cells to the pathophysiology of multiple sclerosis. J Neuroinflammation 16(1):128. https://doi.org/10.1186/s12974-019-1517-1 [3]Bönelt P, Wöhner M, Minnich M et al (2019) Precocious expression of Blimp-1 in B cells causes autoimmune disease with increased self-reactive plasma cells. EMBO J 38(2). pii:e100010. https://doi.org/10.15252/embj.2018100010 Table 1. Clinical characteristics of pSS and HC. HC(n=17 ) pSS(n=50 ) Sex (Male/Female) 0/17 0/50 Age(x± s ) 45.24±18.55 46.8±11.05 Xerostomia(positive/negative) 0/17 43/7 Keratoconjunctivitis sicca 0/17 35/15 Arthralgia 0/17 32/18 Fatigue 0/17 18/32 ESSDAI(x± s ) - 2.78±1.61 (0~7) ESSPRI(x± s ) - 3.3±1.39 (1~6) ANA(positive/negative) - 49/1 SSA - 49/1 SSB - 18/32 pSS: primary sjögren ‘s syndrome; HC: Healthy controls; ESSDAI: The European League Against Rheumatism Sjögren’s Syndrome Disease Activity Index; ESSPRI: EULAR Sjögren’s Syndrome Patient Reported Index.** P&lt;0.01,*** P&lt;0.001. Acknowledgments : This study was supported by the grants from the National Natural Science Foundation of China (81871271). Disclosure of Interests: : None declared