Development of a CENP-A/CENP-B-specific immune response in a patient with systemic sclerosis.
Antibodies directed against an epitope motif on CENP-A have been shown to cross-react with mimotopes on other autoantigens and on Epstein-Barr nuclear antigen 1 (EBNA-1), suggesting a molecular mimicry. We describe here the gradual development of an anticentromere immune response in a patient with systemic sclerosis, which started from an antihistone response and was not mediated by molecular mimicry. Via an epitope on histone H3, the antibody response spread to a homologous epitope in the H3 homology domain of CENP-A. This was followed by an intramolecular epitope spreading to N-terminal peptides of CENP-A containing the known epitope motif G-P-X(1)-R-X(2). From there it spread to corresponding epitopes on CENP-B and to mimotopes of the major CENP-A epitope motif on other autoantigens including EBNA-1. Whether the D-penicillamine treatment received by this patient was involved in the triggering of this cascade remains a matter of speculation.
Mahler
Michael
M
Institute of Molecular Genetics, University of Heidelberg, Heidelberg, Germany.
Mierau
Rudolf
R
Genth
Ekkehard
E
Blüthner
Martin
M
D000328:Adult; D001324:Autoantigens; D000076247:Centromere Protein A; D051936:Centromere Protein B; D002843:Chromatin / Q000276:immunology; D002868:Chromosomal Proteins, Non-Histone / Q000276:immunology*; D004268:DNA-Binding Proteins; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology; D005260:Female; D006801:Humans; D012595:Scleroderma, Systemic / Q000276:immunology*
D001324:Autoantigens; C000619700:CENPA protein, human; C497926:CENPB protein, human; D000076247:Centromere Protein A; D051936:Centromere Protein B; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D000939:Epitopes