A cross-reactive idiotype in scleroderma.
Autoantibodies to centromere proteins (anti-CENPs) and to topoisomerase-I are highly specific for scleroderma. Unlike most autoantibodies in other diseases, these autoantibodies are mutually exclusive. We have analysed the idiotypes (Ids) expressed by anti-CENP-B, antitopoisomerase-I, and IgGs from 20 scleroderma patients. Rabbit anti-Ids were prepared to antitopoisomerase-I from two scleroderma patients, and to anti-CENP-B from four patients. These six anti-Ids were used to study the purified autoantibodies from 20 scleroderma patients: four antitopoisomerase-I, 10 anti-CENP-B, and six purified IgG from scleroderma patients who were negative for both autoantibodies. In addition, we studied sera from 40 normal autoantibody-negative controls, and sera and purified immunoglobulins from 17 systemic lupus erythematosus (SLE) patients containing high titres of anti-double-stranded DNA, and/or autoantibodies to extractable nuclear antigens (ENA). Using direct binding, and competitive inhibition ELISAs and immunoblots, we identified an Id present in the heavy chains of all the affinity-purified antitopoisomerase-I, and anti-CENP-B. Interestingly, this Id was also present in the immunoglobulins of the scleroderma patients who had neither of the two autoantibodies. By contrast, cross-reactive Id-EM was not found in the sera or immunoglobulins from 17 SLE patients, or in the sera from 40 normal subjects. Several samples from two patients showed that this cross-reactive Id-EM was stable over time. The scleroderma disease-specific autoantibodies may be identified through a common structural feature at the variable region of the heavy chain: cross-reactive Id-EM.
Vázquez-Abad
D
D
Department of Medicine, University of Connecticut School of Medicine, Farmington 06030-1310, USA.
Tian
L
L
Zanetti
M
M
Rothfield
N F
NF
D000818:Animals; D001323:Autoantibodies / Q000276:immunology; D001324:Autoantigens; D051936:Centromere Protein B; D002868:Chromosomal Proteins, Non-Histone / Q000276:immunology*; D003429:Cross Reactions; D004264:DNA Topoisomerases, Type I / Q000276:immunology*; D004268:DNA-Binding Proteins; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007130:Immunoglobulin Idiotypes / Q000032:analysis*; D008137:Longitudinal Studies; D011817:Rabbits; D012595:Scleroderma, Systemic / Q000276:immunology*
D001323:Autoantibodies; D001324:Autoantigens; C497926:CENPB protein, human; D051936:Centromere Protein B; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D007130:Immunoglobulin Idiotypes; D004264:DNA Topoisomerases, Type I