Increased CD38 expression in T cells and circulating anti-CD38 IgG autoantibodies differentially correlate with distinct cytokine profiles and disease activity in systemic lupus erythematosus patients

CD38 is a multifunctional protein possessing ADP-ribosyl cyclase activity responsible for both the synthesis and the degradation of several Ca2+-mobilizing second messengers. In mammals, CD38 also functions as a receptor. In this study CD38 expression in CD4+, CD8+, or CD25+ T cells was significantly higher in systemic lupus erythematosus (SLE) patients than in Normal controls. Increased CD38 expression in SLE T cells correlated with plasma levels of Th2 (IL-4, IL-10, IL-13) and Th1 (IL-1β, IL-12, IFN-γ, TNF-α) cytokines, and was more prevalent in clinically active SLE patients than in Normal controls. In contrast, elevated anti-CD38 IgG autoantibodies were more frequent in clinically quiescent SLE patients (SLEDAI = 0) than in Normal controls, and correlated with moderate increased plasma levels of IL-10 and IFN-γ. However, clinically active SLE patients were mainly discriminated from quiescent SLE patients by increased levels of IL-10 and anti-dsDNA antibodies, with odds ratios (ORs) of 3.7 and 4.8, respectively. Increased frequency of anti-CD38 autoantibodies showed an inverse relationship with clinical activity (OR = 0.43), and in particular with the frequency of anti-dsDNA autoantibodies (OR = 0.21). Increased cell death occurred in CD38+ Jurkat T cells treated with anti-CD38+ SLE plasmas, and not in these cells treated with anti-CD38− SLE plasmas, or Normal plasmas. This effect did not occur in CD38-negative Jurkat T cells, suggesting that it could be attributed to anti-CD38 autoantibodies. These results support the hypothesis that anti-CD38 IgG autoantibodies or their associated plasma factors may dampen immune activation by affecting the viability of CD38+ effector T cells and may provide protection from certain clinical SLE features.

Highlights► Increased frequency of CD38+ T cells in clinically active SLE patients vs Normal. ► Increased frequency of anti-CD38 autoantibodies in quiescent SLE patients vs Normal. ► IL-10 and anti-dsDNA levels discriminate active from quiescent SLE patients. ► Negative association of anti-CD38 with anti-dsDNA autoantibodies in active SLE. ► Anti-CD38 autoantibodies may induce CD38+ T-cell death.