Immunohistological techniques were used to identify activated T lymphocytes within the synovial membrane of patients with rheumatoid arthritis, using the monoclonal antibody (MoAb) RFT2, which identifies a 40-k dalton molecule preferentially expressed by T blasts or activated cells. Using this reagent together with a monoclonal 'cocktail' that stains all T cells, cell counts on consecutive sections of rheumatoid synovium revealed that up to 50% T lymphocytes were RFT2+ (range 9.3-50.2%, mean 25.4). Subsequent analysis using combination immunofluorescence demonstrated that over 90% of these activated cells were of the T4+ subset. Furthermore all these cells appeared to be Leu8-, suggesting that the activated population were exclusively 'true helpers' and not suppressor inducers. Studies indicated that 50% of the RFT2+ cells were positive with anti-Tac MoAb. Comparisons with tissues from other arthropathies demonstrated that this relatively high proportion of RFT2+ cells was a feature restricted to rheumatoid arthritis, although biopsies from patients with psoriatic arthritis and ankylosing spondylitis also contained activated cells. Biopsies of Reiter's syndrome, osteo-arthritis, and pigmented villonodular synovitis contained no activated cells, nor were any seen in sections of normal synovium. The presence in rheumatoid synovial membrane of activated T cells which are only of the T4+, Leu8- subset adds weight to the suggestion that local immunoregulatory dysfunction contributes to the chronic inflammation of rheumatoid arthritis.
SUMMARY A prospective study of 33 patients with polymyalgia rheumatica/giant cell arteritis (PMR/GCA) was undertaken, firstly, to monitor sequentially peripheral blood CD8+ lymphocyte levels and, secondly, to assess the expression of activation markers on T lymphocyte subsets. The results indicated that there was a significant decrease in absolute numbers and relative percentages of CD8+ T lymphocytes, which returned to normal ranges after approximately 24 months' treatment, and that there was an increased percentage of CD8+ lymphocytes in PMR/GCA which express HLA class II antigens. We undertook a prospective study of patients with PMR/GCA, firstly, to monitor sequentially peripheral blood CD8+ lymphocyte levels and, secondly, to assess the expression of activation markers (HLA class II antigens and interleukin 2 receptor) on T lymphocyte subsets. Our results indicate that there is a profound decrease in absolute numbers of CD8+ T lymphocytes, which return to the normal range after approximately 24 months' treatment and that most CD8+ lymphocytes express class II antigens.
Patients and methods
PATIENTS AND CONTROLSThirty three patients were investigated. Blood samples were taken sequentially from the onset of disease (and before treatment with corticosteroids) and subsequently every three months up to 24 months. The diagnosis of polymyalgia rheumatica was based on myalgias involving shoulder and pelvic girdle muscle together with morning stiffness and an acute phase reaction (raised C reactive protein and erythrocyte sedimentation rate). Patients with giant cell arteritis were included after a positive temporal artery biopsy. All patients showed rapid and lasting remission of symptoms with corticosteroid treatment
Fifty-nine patients were entered into a double-blind, parallel comparison of the efficacy and side-effects of naproxen sodium (825 mg daily) and indomethacin (100 mg daily) in the treatment of periarthritis of the shoulder joint. Assessments were made on entry to the study, at two weeks, and at the end of four weeks when objective and subjective recordings of mobility, loss of function, pain and the presence of absence of side-effects were noted. The two treatment groups were found to be matched for age, sex and duration of disease, and an assessment at the start of the study differed only in respect of the degree of active medial rotation of the shoulder joint and pain. There was an overall improvement from the time of admission to the study in both the naproxen sodium and the indomethacin treatment groups but there was no significant difference between the efficacy of the two groups. One patient from the naproxen sodium group and three patients from the indomethacin group withdrew from the trial because of side-effects which in each case involved the gastro-intestinal tract.
Frozen sections of pannus tissue taken from the joints of patients with rheumatoid arthritis have been investigated using immunohistological methods to determine the distribution of subsets of macrophage-like cells in this area. A panel of monoclonal antibodies including reagents specific in normal tissue for interdigitating cells (RFD1), macrophages (RFD7), epithelioid cells, (RFD9), monocytes (UCHMI), and osteoclasts (263C), were used. Indirect immunoperoxidase and combination indirect immunofluorescence procedures revealed the phenotypes of macrophage-like cells in four histologically distinct areas of the tissue: the synovial lining layers, the deeper stroma, areas of perivascular infiltration, and the articular cartilage junction where degeneration was occurring. It was discovered that 80% of the lining cells and a majority of macrophage-like cells of the stroma, express the phenotype RFD1+ RFD7+ UCHMI+. Cells with a typical 'dendritic cell' phenotype (RFD1+ RFD7-) were only present in the perivascular infiltrates, while 'classic macrophages' (RFD7+ RFD1-) were the cells accumulating at the cartilage junction. No significant numbers of RFD9+ epithelioid cells were seen. 263C+ osteoclasts were present in small numbers distributed throughout the stroma but did not appear to be involved in areas of cartilage degradation. This cellular distribution in the pannus is compared with previous studies on the rheumatoid synovium proper. It is concluded that a distinct inflammatory reaction occurs in the pannus and that classic activated macrophages are the cells involved in cartilage degradation.
Scleroderma and aplastic anaemia (AA) occurred simultaneously in a patient. Treatment with antilymphocyte globulin (ALG) resulted in some improvement of the scleroderma and a partial, temporary response of the AA. Both the scleroderma and AA then responded dramatically to cyclosporin (CSA) therapy. Subsequently, a positive Ham's test, together with a reduction in the phosphatidyl-inositolglycan (PIG) anchored membrane proteins decay accelerating factor (DAF, CD55) and membrane inhibitor of reactive lysis (MIRL, CD59), confirmed a diagnosis of paroxysmal nocturnal haemoglobinuria (PNH) affecting erythroid, myeloid and lymphoid cell lineages. We hypothesize that the pathogenesis of the bone marrow failure in this patient was a stem cell defect with a secondary immune response involving T-lymphocytes that may have simultaneously triggered the pancytopenia and scleroderma.
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