Patients with rheumatic diseases often have circulating autoantibodies to nuclear components. The clinical significance of the antibodies is controversial, although in some cases they are valuable in the diagnosis of the disease. This report presents results of a study of Scl-70, an autoantigen recognized by sera of many patients with the most severe form of progressive systemic sclerosis. It was possible to show, by three independent criteria, that Scl-70 is the abundant nuclear enzyme DNA topoisomerase I. Therefore, antibody probes of high titer and high affinity are now available for the study of this important nuclear enzyme.
A young woman had a history of spontaneous venous thromboembolic disease which recurred on several occasions after cessation of treatment with oral anticoagulants. The presence of antiphospholipid antibodies (lupus anticoagulant and a high titre of lgG class anticardiolipin antibodies) in the absence of other clinical and serological features of systemic lupus erythematosus (SLE) confirmed a diagnosis of primary antiphospholipid syndrome (PAPS). Antinuclear antibodies (ANA) were positive (1:1280; speckled pattern). Twelve years after the first thrombotic episode she fulfilled criteria for the classification of SLE (antinuclear antibodies, platelet count < 100 x 10(9)/l, anti-dsDNA antibodies, Coombs' positive haemolytic anaemia). She suffered a myocardial infarction while adequately anticoagulated and developed polyarthritis and immune complex-mediated nephritis over the next 3 years. This case history supports suggestions made by others that a strongly positive ANA test in a patient diagnosed with PAPS may be a harbinger for the development of SLE. Such evolution can take place over more than 10 years.
The present study was designed to determine the subcellular localization of histidyl-tRNA synthetase (Jo-1) in human laryngeal epithelial carcinoma cell line (HEp-2 cells). Indirect immunofluorescence using commercial HEp-2 cells with human serum and human-affinity-purified anti-Jo-1 antibodies was performed using confocal microscopy. Anti-histidyl-tRNA-synthetase-positive sera showed distinct nuclear and cytoplasmic granular staining in HEp-2 cells. Affinity purified anti-Jo-1 produced an identical pattern to the whole serum, whereas the serum fraction that did not bind to the affinity column was negative by immunofluorescence on HEp-2 cells. Two commercial human anti-Jo-1-positive control sera and seven anti-Jo-1-positive sera from patients with myositis reproduced the nuclear and cytoplasmic granular pattern. We conclude that Jo-1 is present in cytoplasm and in intact nuclei from HEp-2 cells. The presence of tRNA synthetases in intact nuclei suggests that they have an unsuspected function in the nucleus.
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