title: 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).
abstract: 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.
authors.affiliation: Department of Immunology, The Medical School, University of Newcastle upon Tyne, UK.
authors.forename: J G
authors.initials: JG
authors.lastname: Zhang
authors.forename: L
authors.initials: L
authors.lastname: Morgan
authors.forename: G P
authors.initials: GP
authors.lastname: Spickett
mesh_terms: 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*
chemical_list: D004224:Diterpenes; D007136:Immunoglobulins; D014801:Vitamin A; C031390:9-cis-retinal; D014212:Tretinoin; D015474:Isotretinoin; D012172:Retinaldehyde