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Renal biopsies were performed in 14 patients with severe rheumatoid arthritis who had no evidence of compromised renal function after completion of treatment with low-dose cyclosporine (±5 mg/kg/d). Mean serum creatinine at the time of biopsy was 0.84 mg/dL (range, 0.59 to 1.23 mg/dL). In the 13 patients who had received 6 months of cyclosporine therapy, mild glomerular expansion was noted in two biopsy specimens, obsolescent glomeruli (range, 5% to 20%) in five, and glomerular amyloid deposits in one. Five biopsy specimens had mild and three had mild to moderate interstitial fibrosis. Moderate interstitial fibrosis with a striped pattern was attributed to cyclosporine in the 14th patient. The results of a second biopsy performed in one patient after a further 18 months of therapy were unchanged. Although the renal biopsy changes were minimal in 13 patients and pathologic features characteristic of cyclosporine nephropathy were absent from all but one biopsy, a greater frequency of adverse effects due to cyclosporine could not be excluded. In the absence of clinical data, long-term cyclosporine therapy must be administered with caution to patients with rheumatoid arthritis, who commonly have underlying renal damage, and the value of renal biopsies in predicting and preventing end-stage renal failure remains to be determined.

144 patients with severe rheumatoid arthritis from six centres were randomised to receive oral cyclosporin or placebo for 6 months. The initial daily dose of cyclosporin was 2·5 mg/kg, which was increased cautiously with monitoring of serum cyclosporin levels and creatinine; the mean stabilisation dose was 3·8 mg/kg. There were significant improvements in the cyclosporin-treated patients compared with the controls in the major outcomes of reduction of active joints (23% improvement), pain (24%), and functional status (16%); global improvement was 27%. In the cyclosporin group serum creatinine increased by a mean of 15·6 μmol/l and mean arterial blood pressure by 6·27 mm Hg; these increases were controlled in all but 2 patients by dose adjustment without withdrawal from the study.

In four patients a systemic vasculitis similar to polyarteritis nodosa developed within 2 years of the onset of hairy-cell leukaemia. Arteriographic studies in two patients revealed microaneurysms, and biopsy specimens in three patients revealed a vasculitis affecting medium-sized vessels. Blood neutrophilia and neutrophilic vascular infiltrate were absent. One patient had circulating immune complexes. Two patients responded to corticosteroids alone, one required cyclophosphamide as well as steroids, and one improved without chemotherapy. The association of vasculitis with hairy-cell leukaemia may provide insight into the pathogenesis of arteritis.

Transformation of peripheral blood lymphocytes after exposure to connective tissue antigens was measured in patients with adult (n = 35) and juvenile rheumatoid arthritis (n = 34), osteoarthritis (n = 21), ankylosing spondylitis (n = 15), and systemic lupus erythematosus (n = 26) and in control subjects (n = 36). The connective tissue antigens included homologous cartilage-type proteoglycan, cyanogen bromide-derived peptides of type I, II, and III collagens, and type I and II helical collagens. Lymphocyte transformation was not detected in the osteoarthritic and control groups, with one exception. Sensitization to at least one connective tissue antigen was detected in approximately one-third of the rheumatoid arthritic and lupus patients and in one-quarter of the juvenile rheumatoid patients. In ankylosing spondylitis, positive responses occurred to proteoglycan in 20% of patients tested but never to collagens or peptides. Sensitivity to proteoglycan was detected only in ankylosing spondylitis except for one patient with juvenile rheumatoid arthritis. In patients with systemic lupus erythematosus and both forms of rheumatoid arthritis, lymphocyte transformation was usually more frequently detected to peptides than to the helical collagens. In adult rheumatoid arthritis, type II peptides elicited an elevated number of responses (14%) as did type I (9%) and III (8%) peptides to lesser degrees. Responses to type I (4%) and II (4%) helical collagens were infrequent. Rheumatoid arthritic patients usually exhibited sensitivity to only one antigen and lymphocyte transformation was often detected when the arthritis was improving. In juvenile rheumatoid arthritis, lymphocyte transformation was detected to peptides of type I (16%), II (9%), and III (29%) collagens and to helical type I (12%) and II (8%) collagens. In systemic lupus erythematosus, sensitization was detected to peptides of type I (13%), II (20%), and III (14%) collagens and to helical type I collagen (18%) but not type II collagen. Simultaneous sensitivity to several antigens often occurred in both systemic lupus erythematosus and juvenile rheumatoid arthritis. Examination of individual patients in all three rheumatic disease groups revealed that immune sensitivity developed to collagen peptides rather than to the helical molecules, particularly in the case of type II collagen. Thus, some patients with inflammatory arthritis exhibit immune responses to connective tissue components which are, as a group, characteristic for each type of arthritis. These responses, which were not obviously associated with disease activity, may develop as a result of inflammation or trauma which destroys connective tissue and exposes molecules, in either a native or degraded state, to cells of the immune system. Expression of sensitivity to these tissue antigens may contribute to the chronicity of the inflammatory arthritides.