Identification of autoantibodies to the I protein of the heterogeneous nuclear ribonucleoprotein complex in patients with systemic sclerosis.

Abstract

OBJECTIVE:

To assess the presence of autoantibodies to the 1 protein (polypyrimidine-tract binding protein) of the heterogeneous nuclear RNPs (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), and mixed connective tissue disease (MCTD).

METHODS:

Sera from 101 patients with various connective tissue diseases and 25 normal controls were investigated by enzyme-linked immunosorbent assay and immunoblotting, for their reactivity to highly purified recombinant hnRNP I. Moreover, reactivity to cellular hnRNP I protein was investigated by immunoblotting using a partially purified preparation of hnRNP proteins (including A1, A2, B, and I), and by indirect immunofluorescence. For the analysis of the fluorescence pattern, affinity-purified antibodies to hnRNP 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 32 with RA, 0 of 23 with SLE, and 0 of 6 with MCTD. Antibodies to recombinant 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 anti-hnRNP I autoantibodies gave a diffuse nucleoplasmic staining. Using an hnRNP preparation from nuclear extracts, anti-hnRNP I reactivity was detectable in SSc sera, while it was not detectable in RA, SLE, and MCTD sera reacting with hnRNP A/B proteins.

CONCLUSIONS:

Human autoimmune 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 pre-SSc features, suggesting an early appearance of these antibodies during the course of the disease.

• Authors: C Montecucco, R Caporali, F Cobianchi, G Biamonti
• Journal: Arthritis and rheumatism (Arthritis Rheum) Vol. 39 Issue 10 Pg. 1669-76 (Oct 1996) ISSN: 0004-3591 [Print] United States
• PMID: 8843857 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Autoantibodies
• Heterogeneous Nuclear Ribonucleoprotein A1
• Heterogeneous-Nuclear Ribonucleoprotein Group A-B
• Heterogeneous-Nuclear Ribonucleoproteins
• RNA-Binding Proteins
• Recombinant Proteins
• Ribonucleoproteins
• hnRNP A2
• Polypyrimidine Tract-Binding Protein

Topics

• Autoantibodies (blood, immunology)
• Cell Nucleus (chemistry, immunology)
• Enzyme-Linked Immunosorbent Assay
• Fluorescent Antibody Technique, Indirect
• Gene Expression (immunology)
• Heterogeneous Nuclear Ribonucleoprotein A1
• Heterogeneous-Nuclear Ribonucleoprotein Group A-B
• Heterogeneous-Nuclear Ribonucleoproteins
• Humans
• Polypyrimidine Tract-Binding Protein
• RNA-Binding Proteins (genetics, immunology, isolation & purification)
• Recombinant Proteins (immunology)
• Ribonucleoproteins (genetics, immunology, isolation & purification)
• Scleroderma, Systemic (immunology)