Scleroderma-Polymyositis Overlap Syndrome. : Clinical and Serologic Aspects

Autoantibodies in the serum from a patient with connective tissue disease have been used to define a high molecule weight acidic nuclear protein antigen. The antigen tentatively termed Ku, after the first two letters of patient's name, has distinct physicochemical properties and immunological specificities that distinguish it from previously reported antigens. The Ku antigen has an apparent 300,000 mol wt as determined by gel filtration and sucrose density gradient ultracentrifugation techniques. The antigen is destroyed by trypsin, mild heating, and pH variations greater than 10 and less than 5. Treatment with ribonuclease or deoxyribonuclease did not affect the antigenic reactivity. The Ku antigen was demonstrated in the soluble extracts of human, calf, and rabbit, but not of rat tissues. Purified antibody localized the Ku antigen within the nuclei of human liver where a "reticular" pattern of immunofluorescence was seen. Of 330 patients with various connective tissue diseases, 9 had precipitating antibodies to the Ku antigen. Preliminary results of clinical analysis indicated that antibody to the Ku antigen might become a useful marker for a group of patients with clinical characteristics of both polymyositis and scleroderma with a good prognosis.

In the course of studying antinuclear antibodies in the rheumatic diseases, a new precipitin reaction (provisionally referred to as PM-1) was observed between calf thymus nuclear extract and polymyositis sera. Objectives of this study were to further define the immunologic nature of this reaction and to determine its specificity for polymyositis. Immunodiffusion studies using calf thymus nuclear extract revealed the PM-1 precipitin line in 17 of 28 patients with polymyositis. This reaction was not produced by sera of 460 patients with other diseases. Enzyme and heat treatments of the nuclear extract showed that PM-1 was distinct from native DNA, ribonucleoprotein, and Sm antigens. Fractionation of PM-1-positive serum by 30% ammonium sulphate and Sephadex G-200 chromatography revealed that the factor producing the PM-1 precipitin reaction was in a serum fraction which showed only IgG by immunoelectrphoresis against anti-whole human serum. Because of the apparent strong specificity, the PM-1 system may represent a marker antibody for polymyositis.