Anti-RA33 autoantibodies may recognize epitopes in the N-terminal region of hnRNP-A2 (RA33).
The nuclear autoantigen RA33, which is identical to the A2 protein of the heterogeneous nuclear ribonucleoprotein (hnRNP-A2), is a nucleic acid binding protein of 341 amino acids. The N-terminal part contains two RNA binding domains whereas the C-terminal part consists of a long glycine-rich region starting around amino acid 192. Autoantibodies to hnRNP-A2/RA33 can be detected in 20-40% of sera from RA, SLE and MCTD patients. So far, it has not been known which regions of A2/RA33 are recognized by these autoantibodies. To address this issue, tryptic fragments of natural A2/RA33 were investigated by immunoblotting using 14 sera from anti-RA33 positive patients with RA (n = 5), SLE (n = 5) and MCTD (n = 4). Most sera reacted with a 22 kD fragment comprising the N-terminal part of the protein. However, a smaller 18 kD fragment was recognized only by 3 RA and 3 MCTD sera whereas two of five SLE sera were reactive with two larger fragments of 26 and 29 kD. In order to further characterize the epitope(s) C-terminal deletion mutants of recombinant A2/RA33 were investigated by immunoblotting employing 27 sera from anti-RA33 positive patients with RA (n = 10), SLE (n = 8), and MCTD (n = 9). All sera recognized a fragment terminating at amino acid 212 which contained the complete N-terminal region as well as 20 amino acids of the glycine-rich section. Thus, these data indicate that the N-terminal part of A2/RA33 contains epitopes for antiA2/RA33 autoantibodies.(ABSTRACT TRUNCATED AT 250 WORDS)
Skriner
K
K
Ludwig Boltzmann-Institute for Rheumatology and Balneology, Lainz Hospital, Vienna, Austria.
Steiner
G
G
Sommergruber
W H
WH
Sinski
A
A
Smolen
J S
JS
D034961:Antigens, Nuclear; D001323:Autoantibodies / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology*; D000939:Epitopes / Q000032:analysis*; D017353:Gene Deletion; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D006801:Humans; D015151:Immunoblotting; D009687:Nuclear Proteins / Q000276:immunology*; D012261:Ribonucleoproteins / Q000235:genetics / Q000276:immunology*
D034961:Antigens, Nuclear; D001323:Autoantibodies; D001324:Autoantigens; D000939:Epitopes; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D009687:Nuclear Proteins; D012261:Ribonucleoproteins; C439768:hnRNP A2