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THU0242 (2020)
REGULATORY ROLE OF TRANSCRIPTION FACTOR BLIMP-1 IN SJÖGREN’S SYNDROME
R. Wu1, L. Wang1, X. Zheng1, Y. Wang2, G. Wang1, X. Li1, X. Li1
1The First Affiliated Hospital of China University of Science and Technology, Hefei, China
2Westmead Insitute for Medical Research, the University of Sydney, NSW, Australia

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 <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 <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 ).

(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.

(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<0.05, ***p<0.001.

(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<0.01, ***p<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

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<0.01,*** P<0.001.


Acknowledgments : This study was supported by the grants from the National Natural Science Foundation of China (81871271).


Disclosure of Interests : None declared


Citation: Ann Rheum Dis, volume 79, supplement 1, year 2020, page 344
Session: SLE, Sjön’s and APS - etiology, pathogenesis and animal models (Poster Presentations)