Antibodies to Sm and RNP antigens have been detected by immunoblotting and immunoprecipitation of small nuclear ribonucleoproteins in 168 sera from patients with connective tissue diseases previously characterized by immunodiffusion. Anti-RNP and anti-Sm antibodies immunoprecipitated U1 and U1-U6 snRNA respectively. By immunoblotting anti-Sm reacted with B-B' and D polypeptides and we have distinguished two types of anti-RNP sera: 1) 'full spectrum' anti-RNP sera reacted with the 68 kD, A, C and B-B' polypeptides; 2) 'partially reactive' anti-RNP sera reacted with various combinations of these polypeptides but not the four of them. A strong specificity of anti-Sm antibodies for systemic lupus erythematosus (SLE) was found with all three methods but immunoblotting was more sensitive and detected anti-Sm in 76% of SLE sera. Sera containing a high titer of 'full spectrum' anti-RNP without anti-Sm activity were only detected in mixed connective tissue disease (MCTD) whereas anti-68 kD antibodies alone seemed to be less specific. This strong association between 'full spectrum' anti-RNP antibodies and MCTD supports the hypothesis that MCTD is a distinct clinical entity associated with a specific serologic marker.
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