In a follow up study of 11 patients with mixed connective tissue disease the levels of antibodies to nuclear ribonucleoprotein (nRNP) as measured by an enzyme linked immunosorbent assay (ELISA) were related to clinical activity of disease. To assess the relation between anti-nRNP levels and disease activity the levels of total immunoglobulin G, IgM rheumatoid factor (IgM RF), and antibodies to an unrelated antigen (tetanus toxoid) were determined simultaneously. No significant changes in anti-nRNP levels were noted in four patients with minor activity of disease. Major flares of disease were observed in seven patients. Clinical symptoms were preceded by a rise in anti-nRNP level in these patients unless they received immunosuppressive agents before the exacerbation. Conversely, when a rise in anti-nRNP level occurred a major flare of disease was followed in all but one case. Anti-nRNP levels fell during clinical improvement whether or not immunosuppressive treatment was given. All patients showed parallel fluctuations in anti-nRNP, IgM RF, and total immunoglobulin G levels. Furthermore, parallel fluctuations were seen in the levels of anti-nRNP and antibodies to tetanus toxoid except in one patient. We conclude that measurement of anti-nRNP by ELISA may be a guide for disease activity in connective tissue disease. Fluctuations of anti-nRNP are not restricted to this antibody, however, but are part of a more polyclonal activity of the B lymphocyte system.
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