Mixed connective tissue disease-an apparently distinct rheumatic disease syndrome associated with a specific antibody to an extractable nuclear antigen (ENA)

Abstract

We describe the clinical and serologic findings in twenty-five patients with an apparently distinct rheumatic disease syndrome which we have termed mixed connective tissue disease. All these patients had hemagglutinating antibody to an extractable nuclear antigen (ENA) which consists mainly of protein and ribonucleic acid (RNA). A marked sensitivity of the hemagglutination antigen to ribonuclease indicated that the specificity of the antibody to ENA circulating in these patients was different from that of antibody to ENA which occurred in about 50 per cent of the patients with systemic lupus erythematosus. Serum from patients with mixed connective tissue disease also contained high titers of speckled pattern fluorescent antinuclear antibody which showed the same response of tissue antigens to enzyme digestion as found with hemagglutinating antibody. There was no detectable Sm antibody. Antibody to native deoxyribonucleic acid (DNA) was infrequent and of low titer, and serum complement levels were normal or elevated. The clinical characteristics of the patients with mixed connective tissue disease included a combination of features similar to those of systemic lupus erythematosus, scleroderma and polymyositis. Most of these abnormalities were responsive to corticosteroid therapy. Thus, the detection of antibody to ENA with a well defined specificity allows recognition of an apparently distinct mixed connective tissue disease syndrome which is characterized by an excellent response to corticosteroid therapy and a favorable prognosis.