Vitamin D-3 and its synthetic analogs inhibit the spontaneous in vitro immunoglobulin production by SLE-derived PBMC

The production of high-affinity pathogenic autoantibodies in systemic lupus erythematosus (SLE) may result from aberrant immune regulation. Since 1,25 dihydroxy vitamin D-3 (1,25 D-3) has immunoregulatory activity, we examine d effects of 1,25 D-3 and its analogs HM, V, MC1288, and KH1060 on autoanti body production and proliferation of SLE: PBMC. We found, in SLE, a higher percentage of T, B, and NK expressing vitamin D-3 receptors (VDRs) (P = 0.0 34, 0.006, 0.012, respectively). Incubating SLE PBMC with 1,25 D-3 compound s significantly reduced proliferation, polyclonal and anti-dsDNA IgG produc tion, and the percentages of CD3(+)/DR+ T and B (CD19(+)) cells, while elev ating NK (CD16(+)) cells (P < 0.001). 1,25 D-3 analogs were more potent tha n the natural compound: KH1060 up-regulated CD14 expression by SLE monocyte s (P < 0.001), inhibited polyclonal and anti-dsDNA IgG production by SLE-de rived B lymphoblasts, and induced apoptosis of activated B lymphoblasts. Th ese data suggest that 1,25 D-3 compounds can offer novel approaches to the clinical management of SLE. (C) 2001 Academic Press.