Analysis of impaired in vitro immunoglobulin synthesis in rheumatoid arthritis

Abstract

Decreased immunoglobulin production in pokeweed mitogen driven lymphocyte cultures has been reported in rheumatoid arthritis (RA). Here various activators and experimental designs have been used to determine the contribution of B cells, T cells, or monocytes to this low response. Sixty patients with RA and paired controls were studied at the onset of disease and again six months later. Concentrations of IgA, IgG, and IgM in cultures of RA peripheral blood mononuclear cells stimulated with thymus dependent activators were already decreased at the onset of the disease. Six months later RA mononuclear cells produced even lower concentrations of immunoglobulin. In contrast, stimulation with a T cell independent activator showed that RA B lymphocytes had retained normal potential to synthesise immunoglobulin. Poor helper function was indicated by costimulation experiments and cultures of mixed mononuclear cells from patients and controls. This notion was supported also by the fact that phytohaemagglutinin induced interleukin-2 production by RA mononuclear cells was less than half of the control values. Nonspecific suppressor activity was similar in RA and controls. Monocyte functions were normal when tested by addition of indomethacin or 2-mercaptoethanol to the mitogen activated cultures. The defect in mitogen stimulated immunoglobulin production in vitro of RA mononuclear cells thus was more pronounced with time and probably reflects impaired mediator associated help in the differentiation of B lymphocytes into immunoglobulin secreting cells.