Immune Function in Severe , Active Rheumatoid Arthritis

The immunohistology of synovium from a tender, swollen knee and peripheral blood cellular immune function were correlated in 24 clinically similar patients with active, seropositive rheumatoid arthritis who were not taking cytotoxic or long-acting antirheumatic drugs. The patients were classified as anergic (n = 6) or nonanergic (n = 18) on the basis of peripheral blood mononuclear cell proliferative responses to a battery of soluble recall antigens. The peripheral blood mononuclear cells of anergic patients failed to respond significantly to any soluble recall antigen, whereas cells from nonanergic patients responded to at least one such antigen. Multiple pieces of synovial tissue were obtained from each patient at arthroscopy. To minimize intrajoint variability, all pieces were analyzed and averaged to determine a composite profile of abnormalities. Synovial specimens from all six anergic patients had "high intensity" lymphocytic infiltration (group A). In sharp contrast, synovial specimens from 15 of 18 nonanergic patients had "low intensity" lymphocytic infiltration (group B) (P = 0.002). Group A tissues typically showed higher intensity T cell and plasma cell infiltration, more synovial lining layer hyperplasia, more HLA-DR bearing cells, and a higher ratio of Leu 3A/Leu 2A T cells than did group B. Group B tissues had fewer infiltrating cells (most of which were OKM1 and HLA-DR bearing), Received for publication 3 January 1984 and in revised form 1I June 1984. The Journal of Clinical Investigation, Inc. Volume 74, October 1984, 1173-1185 more extensive fibrin deposition, and far fewer T and plasma cells. Although these data do not imply that synovium from different joints in an individual patient are immunohistologically identical, they do provide evidence that peripheral blood mononuclear cell immune function reflects immunopathologic events in the biopsied joint. Moreover, the data further support the view that clinically active rheumatoid arthritis is, like certain other chronic inflammatory conditions, a heterogeneous disorder with polar subgroups.