Expression And Significance Of Transcription Factor Blimp1 In Primary Sj?gren's Syndrome

Objectives: Primary sj?gren's syndrome(pSS)is a multifactor-mediated autoimmune disease characterized by spontaneous antibody and hyperimmunoglobulinemia,and B cells are the cellular basis of both.B lymphocyte induced maturation protein 1(Blimp1)is encoded by PR domain containing protein 1(PRDM1)gene which participated in the activation,function and survival of immunocyte.Blimp1 have been identified as a susceptibility gene for autoimmune diseases.In this study,we analyzed the PRDM1 mRNA expression in pSS and the correlation between PRDM1 mRNA and B cell subsets,clinical indicators to explore the possible molecular mechanism of Blimp1 in the pathogenesis of pSS and provide a new therapeutic target for pSS.Methods: Refer to the reference range of immunoglobulin(Ig)given by the clinical laboratory,patients were assigned to the high Ig group if any one of the following three criteria was satisfied:(1)Ig A>5g/L,(2)Ig G>16g/L,(3)Ig M>1.8 g/L,others were assigned to the normal Ig group.Seventeen age and gander matched women from physical examination center were selected as the healthy controls.CD19+cells population were sorted by magnetic bead sorting technology.The PRDM1 mRNA expression in B cells and labial gland were examined by RT-PCR.The levels of B cells,plasma cells and memory B cells were examined by flow cytometry.Hematoxylin-eosin staining and immunohistochemistry were used to examine the invasion degree of lymph cells and Blimp1 distribution.The correlation of PRDM1 mRNA with B cell subsets and clinical indicators were analyzed by Pearson/Spearman correlation test.Results:(1)PRDM1 mRNA expression:The PRDM1 mRNA expression was higher in pSS group than in HC group(t=3.426;P=0.001),and it was also higher in the high immunoglobulin(Ig)group than normal Ig group(t=2.910;P=0.004).(2)Percentage of B cell subsets:The percentages of B cells and plasma cells increased while the memory B cells decreased in pSS group(P<0.05).(3)Correlation between PRDM1 mRNA and B cell subsets:The percentages of plasma cells and plasma/B cells ratio were positively correlated with PRDM1 mRNA expression(r=0.380,P=0.002;r=0.317,P=0.009).(4)Expression of Blimp1 in labial gland:Blimp1 accumulated predominantly in the germinal center and lymphocytes around the duct and acinus in pSS.PRDM1 mRNA level was positively correlated with invasion degree of lymph cell in histology(r=0.718,P<0.001).(5)Analysis of PRDM1 mRNA expression and clinical features:The ANA titer and ESSDAI score were higher in high Ig group than normal Ig group(P<0.01).PRDM1 mRNA expression was significantly increased in patients with high ANA(antinuclear antibody)titer(ANA>1:320)and disease activity group(P<0.05).PRDM1 mRNA expression was positively correlated with Ig levels and ESSDAI score(r=0.341,P=0.016;r=0.283,P=0.047;r=0.541,P<0.001),but inversely correlated with the daily dose of glucocorticoid(r=-0.658,P<0.001).Conclusion: Blimp1 may promote the occurrence and further induce pSS by upregulating the differentiation of plasma cells,Ig secretion,and self-antibody production.The effect of glucocorticoid in pSS may relate to the inhibition of Blimp1 expression and plasma cells differentiation.