A genome-scale assessment of peripheral blood B-cell molecular homeostasis in patients with rheumatoid arthritis.
Peripheral blood mononuclear cells (PBMC) from 30 patients with definite or classic active rheumatoid arthritis who were on no remittive drugs were studied for spontaneous and pokeweed mitogen (PWM)-stimulated immunoglobulin plaque-forming cell frequency (IgPFC), spontaneous IgM-rheumatoid factor (IgM-RF) secretion, and in vitro proliferative responses to soluble recall antigens. Rheumatoid spontaneous total (IgG + IgM + IgA) IgPFCs were higher than those of normal controls when assayed after 7 days in culture. Spontaneous and PWM-stimulated IgM-PFCs, in contrast, were significantly less than normal regardless of when assayed. Spontaneous synthesis of IgM-RF was observed in 56% of the RA patients, but absolute amounts produced were widely heterogeneous. Spontaneous IgM-RF production by RA PBMC was associated with low or absent spontaneous IgM-PFC production. Moreover, a strong association was found between the median amount of IgM-RF secreted and depressed proliferative responses to soluble recall antigens. Our results define several abnormalities of immunoglobulin production in a clinically homogeneous and highly active rheumatoid population and delineate methodologic variations that can complicate the interpretation of similar data in the literature. In addition, our findings suggest that subgroups of rheumatoid patients that show distinct cellular and humoral immune abnormalities can be identified.