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 examined effects of 1,25 D(3) and its analogs HM, V, MC1288, and KH1060 on autoantibody 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 = 0.034, 0.006, 0.012, respectively). Incubating SLE PBMC with 1,25 D(3) compounds significantly reduced proliferation, polyclonal and anti-dsDNA IgG production, and the percentages of CD3(+)/DR(+) T and B (CD19(+)) cells, while elevating NK (CD16(+)) cells (P < 0.001). 1,25 D(3) analogs were more potent than the natural compound: KH1060 up-regulated CD14 expression by SLE monocytes (P < 0.001), inhibited polyclonal and anti-dsDNA IgG production by SLE-derived B lymphoblasts, and induced apoptosis of activated B lymphoblasts. These data suggest that 1,25 D(3) compounds can offer novel approaches to the clinical management of SLE.
Linker-Israeli
M
M
Department of Medicine, The Cedars-Sinai Research Institute and UCLA, Los Angeles, California 90048, USA. linker@csmc.edu
Elstner
E
E
Klinenberg
J R
JR
Wallace
D J
DJ
Koeffler
H P
HP
D000974:Antibodies, Antinuclear / Q000276:immunology; D017209:Apoptosis / Q000187:drug effects; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology; D015850:Interleukin-6 / Q000096:biosynthesis; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects; D018167:Receptors, Calcitriol / Q000032:analysis
D000974:Antibodies, Antinuclear; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D015850:Interleukin-6; D018167:Receptors, Calcitriol; C074279:KH 1060; D015847:Interleukin-4; D002117:Calcitriol