ANTIBODIES AGAINST DISTINCT NUCLEAR MATRIX PROTEINS ARE CHARACTERISTIC FOR MIXED CONNECTIVE-TISSUE DISEASE

  • 1 January 1983
    • journal article
    • research article
    • Vol. 54  (1) , 265-276
Abstract
Specific nuclear proteins, separated according to their MW by polyacrylamide gel electrophoresis (PAGE) and subsequently transferred to nitrocellulose sheets, are able to bind antibodies in sera from patients suffering from different types of connective tissue diseases. Antibodies against a characteristic set of nuclear protein antigens are found in sera from patients with mixed connective tissue disease (MCTD). Screening of 21 MCTD sera revealed a typical immunoblot pattern with major protein antigens of MW 70,000 (20/21) (not identical with the Scl-70 antigen characteristic for scleroderma), MW 31,000 (17/21), 2 proteins around MW 23,000 (15/21) and 2 around MW 19,000 (10/21). The 70,000, 23,000 and 19,000 antigens appeared to be rather insoluble nuclear proteins (i.e., components of the nuclear matrix). On behalf of their structural character they were present in nuclei from several types of cells but only in low amounts detectable in salt extracts of thymus acetone powder. The presence of antibodies directed against the MW 70,000 antigen correlated strongly with the diagnosis of MCTD. This 70,000 antigen is not identical with the RNP [ribonucleoprotein] antigen, a soluble ribonuclease sensitive RNP, since antibodies against nuclear RNP can be separated from anti-nuclear matrix antibodies by affinity chromatography using immobilized thymus salt extract. The distinct character of soluble nuclear RNP and structural nuclear matrix antigens is further supported by the fact that from 14 other anti-RNP sera obtained from patients with systemic lupus erythematosus (SLE), only 3 contained antibodies against the MW 70,000 protein. Since the immunoblot pattern obtained with MCTD sera mostly was clearly distinguishable from the patterns obtained with sera from patients with related connective tissue diseases the results suggest that the immunoblotting technique might be useful as a diagnostic tool and support the concept of MCTD as a distinct entity.