IDENTIFICATION OF AUTOANTIBODIES TO THE I-PROTEIN OF THE HETEROGENEOUS NUCLEAR RIBONUCLEOPROTEIN COMPLEX IN PATIENTS WITH SYSTEMIC-SCLEROSIS

Objective. To assess the presence of autoantibodies to the I protein ( polypyrimidine-tract binding protein) of the heterogeneous nuclear RNP s (hnRNP) in different connective tissue diseases. Antibodies to other hnRNP proteins (A1, A2, and B) have been previously found in patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), a nd mixed connective tissue disease (MCTD). Methods. Sera from 101 pati ents with various connective tissue diseases and 25 normal controls we re investigated by enzyme-linked immunosorbent assay and immunoblottin g, for their reactivity to highly purified recombinant hnRNP I. Moreov er, reactivity to cellular hnRNP I protein was investigated by immunob lotting using a partially purified preparation of hnRNP proteins (incl uding A1, A2, B, and I), and by indirect immunofluorescence. For the a nalysis of the fluorescence pattern, affinity-purified antibodies to h nRNP I, obtained from a selected patient, were tested on HEp-2 cells. Results. By immunoblotting, antibodies reacting to recombinant hnRNP I were found in 22 of 40 patients with systemic sclerosis (SSc), 3 of 3 2 with RA, 0 of 23 with SLE, and 0 of 6 with MCTD. Antibodies to recom binant hnRNP I were more frequently found in patients with pre-SSc or limited SSc (15 of 24) than in those with intermediate or diffuse SSc (7 of 16). In indirect immunofluorescence studies, affinity-purified a nti-hnRNP I autoantibodies gave a diffuse nucleoplasmic staining. Usin g an hnRNP preparation from nuclear extracts, anti-hnRNP I reactivity was detectable in SSc sera, while it was not detectable in RA, SLE, an d MCTD sera reacting with hnRNP A/B proteins. Conclusion. Human autoim mune sera show distinct patterns of anti-hnRNP reactivity, i.e., anti- A/B in SLE and RA sera, and anti-I in SSc sera. This suggests that A/B proteins and the I protein may be involved in different dynamic hnRNP complexes that elicit different autoimmune responses. From a clinical perspective, anti-hnRNP I antibodies are frequently associated with p re-SSc features, suggesting an early appearance of these antibodies du ring the course of the disease.