In vitro immunoglobulin production by mononuclear cells in rheumatoid arthritis.
Since patients with rheumatoid arthritis (RA) exhibit serum hypergammaglobulinemia and autoantibody (rheumatoid factor) production, we compared elaboration and control of in vitro RA mononuclear cell (MNC), Ig assayed by enzyme-linked immunoassays or by hemolytic plaque formation, in 37 RA patients and 17 normal subjects. We found (1) RA spontaneous plaque-forming cells were significantly reduced (RA 344 vs normal 627 PFC/10(6) MNC, P less than 0.002); (2) RA spontaneous IgG and IgM (but not IgA) elaboration was significantly diminished (IgG RA 339, normal 776; IgM RA 255, normal 869 ng/ml, P less than 0.001; IgA RA 87, normal 124); (3) RA stimulated IgG and IgM production (but not IgA) was also decreased (IgG RA 2434, normal 3862, P less than 0.06; IgM RA, 1676, normal 3323, P less than 0.005; IgA RA 1859, normal 2315); (4) reduced RA Ig elaboration was not clearly due to altered numbers of T or non-T cells, age, medications, clinical features of disease, or response kinetics; (5) relative improvement of RA in vitro IgG, but not usually IgM, secretion followed removal of adherent cells, addition of indomethacin or addition of mitomycin C-treated T cells; (6) MNC from synovial fluids, but not bone marrows, exhibited spontaneous Ig production in excess of stimulated synovial fluid cellular or peripheral blood Ig elaboration. These observations indicate selective impairment of peripheral blood MNC IgG and, particularly, IgM secretion in RA. This defect appears to reflect accessory cell influences which differ from normal as well as the sequestration of primed or activated cells in the synovial fluid.
D000328:Adult; D000368:Aged; D000921:Antibody-Producing Cells / Q000145:classification / Q000276:immunology*; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D001854:Bone Marrow Cells; D002448:Cell Adhesion; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006462:Hemolytic Plaque Technique; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis / Q000096:biosynthesis*; D007075:Immunoglobulin M / Q000032:analysis / Q000096:biosynthesis*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D013582:Synovial Fluid / Q000166:cytology; D013601:T-Lymphocytes / Q000276:immunology
D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007213:Indomethacin