The effects of vitamin A derivatives on in vitro antibody production by peripheral blood mononuclear cells (PBMC) from normal blood donors and patients with common variable immunodeficiency (CVID).
The underlying nature of the defect of CVID is not understood, and the treatment at present is life-long infusion of replacement immunoglobulin. Attempts have been made to use other therapeutic agents, such as IL-2 and retinoic acid (RA), with mixed results. RA is a morphogenetic signalling molecule related to vitamin A and involved in vertebrate development. We report here our in vitro evaluation of the effects of three vitamin A analogues, 9-cis retinal, 13-cis RA and all-trans RA, on antibody production of PBMC from normal donors and patients with CVID. At 10(-5) M, 9-cis retinal strongly augmented IgM production of lymphocytes from normal individuals and to a much lesser extent, mild, non-granulomatous (group C) CVID patients, but IgG production was not affected. In the presence of anti-human IgM and IL-2, 9-cis retinal at 10(-5) M elevated IgM and IgG production by normal PBMC, but the effect on PBMC of mild CVID was minimal. The effect of 9-cis retinal was significantly reduced at 10(-7) and 10(-9) M. Only minimal effects were found using 13-cis RA and all-trans RA under these conditions. No detectable antibody production was found in severe, granulomatous (group A) CVID patients under any conditions tested. Taking all data into account, 9-cis retinal is the most potent stimulator for antibody production compared with 13-cis RA and all-trans RA as tested in this in vitro study.
Zhang
J G
JG
Department of Immunology, The Medical School, University of Newcastle upon Tyne, UK.
Morgan
L
L
Spickett
G P
GP
D001782:Blood Donors; D002478:Cells, Cultured; D017074:Common Variable Immunodeficiency / Q000097:blood / Q000276:immunology*; D004224:Diterpenes; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis* / Q000097:blood / Q000187:drug effects*; D015474:Isotretinoin / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D012172:Retinaldehyde / Q000494:pharmacology; D014212:Tretinoin / Q000494:pharmacology; D014801:Vitamin A / Q000031:analogs & derivatives* / Q000494:pharmacology*
D004224:Diterpenes; D007136:Immunoglobulins; D014801:Vitamin A; C031390:9-cis-retinal; D014212:Tretinoin; D015474:Isotretinoin; D012172:Retinaldehyde