Development of a CENP-A/CENP-B-specific immune response in a patient with systemic sclerosis.

Abstract

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.

• Authors: Michael Mahler, Rudolf Mierau, Ekkehard Genth, Martin Blüthner
• Journal: Arthritis and rheumatism (Arthritis Rheum) Vol. 46 Issue 7 Pg. 1866-72 (Jul 2002) ISSN: 0004-3591 [Print] United States
• PMID: 12124871 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Autoantigens
• CENPA protein, human
• CENPB protein, human
• Centromere Protein A
• Centromere Protein B
• Chromatin
• Chromosomal Proteins, Non-Histone
• DNA-Binding Proteins
• Epitopes

Topics

• Adult
• Autoantigens
• Centromere Protein A
• Centromere Protein B
• Chromatin (immunology)
• Chromosomal Proteins, Non-Histone (immunology)
• DNA-Binding Proteins
• Enzyme-Linked Immunosorbent Assay
• Epitopes (immunology)
• Female
• Humans
• Scleroderma, Systemic (immunology)