In a previous study, we used an enzyme‐linked immunosorbent assay to measure soluble human interleukin‐2 receptors (IL‐2R), and found that when activated lymphocytes produce cell‐associated IL‐2R, they also release a soluble form of IL‐2R into culture supernatants in vitro. Soluble IL‐2R have also been detected circulating in vivo at low levels in the serum of healthy individuals, and at abnormal levels in a variety of diseases, particularly those where immune dysfunction is thought to play an important role. We therefore evaluated serum IL‐2R levels in 77 patients with rheumatoid arthritis (RA), and compared them with levels in 46 age‐matched healthy controls. Nineteen additional RA patients with concurrently obtained sera and synovial fluid (SF) samples were compared with 14 patients with osteoarthritis of the knee or hip. The serum IL‐2R levels were significantly elevated in RA patients, compared with the control groups (P < 0.0001). Serum IL‐2R levels in the RA patients did not correlate with disease activity as determined by a variety of clinical and laboratory parameters. RA SF IL‐2R levels were significantly higher than corresponding RA serum IL‐2R levels (P = 0.0001). No such difference was noted in the osteoarthritis group, where serum and SF IL‐2R levels were comparable with serum levels in healthy controls. These findings support the hypothesis that in vivo lymphocyte activation plays an important role in RA; moreover, soluble IL‐2R measurement in serum and SF may be a very useful way to identify patients at risk for, or manifesting, a chronic immune‐mediated inflammatory arthropathy.

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We examined regulation of Epstein-Barr virus-induced plaque-forming cell generation in peripheral blood mononuclear cells from several autoimmune and seronegative diseases and correlated these results with Epstein-Barr virus-induced proliferation. We confirmed the defective regulation of Epstein-Barr virus-induced plaque-forming cells in peripheral blood mononuclear cells of patients with rheumatoid arthritis and scleroderma. Peripheral blood mononuclear cells from patients with seronegative arthropathies and chronic infective inflammation (cystic fibrosis) had normal regulation of Epstein-Barr virus-induced plaque-forming cells. Peripheral blood mononuclear cells from rheumatoid arthritis had excessive plaque-forming cell generation in the face of a normally regulated decrease in Epstein-Barr virus-induced proliferation. In contrast, peripheral blood mononuclear cells from scleroderma had defective suppression of both Epstein-Barr virus-induced proliferation and plaque-forming cell generation. Thus, impaired regulation of Epstein-Barr virus-induced plaque-forming cell generation is a common feature of autoimmune disease and demonstrates some specificity for these disorders.

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SUMMARY The production of interferon‐gamma (IFN‐γ) by peripheral blood mononuclear cells (PBMC), CD4 cells, or CD8 cells in response to interleukin‐2 (IL‐2) stimulation has been studied; the samples were obtained from 12 healthy control subjects, 19 patients with Graves' disease (10 hyperthyroid and nine euthyroid), 13 patients with Hashimoto's thyroiditis (four hypothyroid and nine euthyroid), and 15 patients with rheumatoid arthritis (11 active and four inactive). A dose of IL‐2 (25 U/ml) was utilized to induce IFN‐γ by PBMC from all four groups. The incremental increase in IFN‐γ values (with IL‐2 stimulation minus without stimulation) was significantly less in PBMC from patients with Graves' disease, Hashimoto's thyroiditis, and rheumatoid arthritis than that in PBMC from control subjects. The values from PBMC in patients with Graves' disease in a euthyroid state were below normal but greater than those from patients with Graves' disease in a hyperthyroid state. The incremental increase in IFN‐γ values from Graves' disease PBMC correlated with the serum TSH values (r=0.622, P < 0.01), but not with thyroid autoantibodies (anti‐thyroid microsomal antibodies, anti‐thyroid microsomal antibodies, nor TSH‐binding inhibitory immunoglobulin activities). The incremental increase in IFN‐γ from PBMC from both control subjects and Graves* disease was correlated with that from CD4 cells (r=0.711, P < 0.01), but not with that from CD8 cells. The production of IFN‐γ in response to IL‐2 from PBMC in Graves' disease correlated inversely with thyroid function, appearing to reflect the very effect of hyperthyroidism in this process. The precise explanation of these phenomena remains unclear. The decreased response of IFN‐γ to IL‐2 stimulation by PBMC from patients with Graves' disease, Hashimoto's thyroiditis, and rheumatoid arthritis seems to be a non‐specific phenomenon occurring in both organ specific autoimmune disease and systemic autoimmune disease. It may be due to a down‐regulation in autoimmune disease of CD4 cells in response to IL‐2, a decreased level of IL‐2 cellular receptors or a decreased receptor affinity, associated increased soluble IL‐2 receptors, or a defect of the intra‐CD4 cellular IL‐2 signal to produce or release IFN‐γ in the conditions studied.

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