Immune function in severe, active rheumatoid arthritis: a relationship between peripheral blood mononuclear cell proliferation to soluble antigens and mononuclear cell subset profiles.

We have previously reported that patients with active rheumatoid arthritis and depressed in vitro peripheral blood mononuclear cell proliferation to soluble recall antigens (anergic subgroup) improve clinically after repeated short-term leukapheresis, whereas patients with normal responses (nonanergic subgroup) do not. This observation prompted us to examine the mononuclear cell subset profiles in the peripheral blood of anergic and nonanergic seropositive rheumatoid arthritis patients with severe, active, clinically similar disease not taking long-acting anti-rheumatic drugs. In the present study, 42 patients were categorized as anergic (n = 14) or nonanergic (n = 28) on the basis of in vitro peripheral blood mononuclear cell proliferation to soluble recall antigens. The anergic patients had a decreased frequency of OKT4+ mononuclear cells (p less than 0.01), and an increased frequency of OKT8+ cells (p less than 0.02), with a lower OKT4+ :OKT8+ ratio (p less than 0.01) than the nonanergic patients. Anergic patients also had a higher frequency of HLA-DR+ mononuclear cells and HLA-DR+ T cells (p less than 0.001). About 50% of the OKT8+ cells were HLA-DR+, whereas only about 20% of the OKT4+ population expressed HLA-DR antigens. These data suggest that the decreased lymphocyte function described in the anergic patient subgroup is associated with characteristic peripheral blood mononuclear cell subset profiles. Moreover, when considered in the context of other data indicating that anergic patients have characteristic synovial immunopathologic abnormalities, these data provide insight into potential pathogenic mechanisms of this disorder.