Elevated STAT1 expression but not phosphorylation in lupus B cells correlates with disease activity and increased plasmablast susceptibility.

OBJECTIVES:SLE is characterized by two pathogenic key signatures, type I IFN and B-cell abnormalities. How these signatures are interrelated is not known. Type I-II IFN trigger activation of Janus kinase (JAK) - signal transducer and activator of transcription inhibition is an attractive therapeutic possibility for SLE. We assess and expression and phosphorylation at baseline and after IFN type I and II stimulation in B-cell subpopulations of SLE patients compared with other autoimmune diseases and healthy controls (HD) and related it to disease activity. METHODS:Expression of duanyu18133 and in B and T cells of 21 HD, 10 rheumatoid arthritis (RA), seven primary Sjögren's (pSS) and 22 SLE patients was analysed by flow cytometry. duanyu18131 and duanyu18133 expression and phosphorylation in PBMCs (peripheral blood mononuclear cells) of SLE patients and HD after IFNα and IFNγ incubation were further investigated. RESULTS:SLE patients showed substantially higher duanyu18131 but not in B- and T-cell subsets. Increased duanyu18131 expression in B-cell subsets correlated significantly with SLEDAI and Siglec-1 on monocytes, a type I IFN marker. duanyu18131 activation in plasmablasts was IFNα dependent while monocytes exhibited dependence on IFNγ. CONCLUSION:Enhanced expression of duanyu18131 by B-cell candidates as a key node of two immunopathogenic signatures (type I IFN and B-cells) related to important immunopathogenic pathways and lupus activity. We show that duanyu18131 is activated upon IFNα exposure in SLE plasmablasts. Thus, Jak inhibitors, targeting JAK-duanyu1813 pathways, hold a promise to block duanyu18131 expression and control plasmablast induction in SLE.

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