title: Autoepitopes on autoantigen centromere protein-A (CENP-A) are restricted to the N-terminal region, which has no homology with histone H3.
abstract: Anti-centromere autoantibodies (ACA) are commonly found in the serum of patients with a limited type of scleroderma and other systemic autoimmune diseases. CENP-A is one of the major antigens against ACA and a histone H3-like protein. To analyse the autoantigenic epitopes of CENP-A, a series of truncated peptides of human CENP-A were expressed in Escherichia coli and immunoblotting analysis was performed with 91 ACA+ sera. Eighty sera (88%) with the ACA reacted to the 52-amino acids N-terminal region which is not homologous to H3, while no sera reacted to the C-terminus which has a sequence similarity with H3. Moreover, ELISA was also employed in this study using two synthetic peptides corresponding to the amino acid sequences 3-17 (peptide A) and 25-38 (peptide B). Peptides A and B were reactive to 78 (86%) and 79 (87%) of ACA, respectively. Core antigens of hepatitis B virus (HBV) and hepatitis C virus (HCV) have similar sequences to peptide A and/or peptide B, but three sera containing HBV without ACA and five sera containing HCV without ACA were found to be reactive to neither peptide. Centromere localization of CENP-A is dependent on the H3-like C-terminal domain which is not autoantigenic, while the antigenic N-terminal domain, which might play unidentified functional roles, should be an important region for the induction of ACA.
authors.affiliation: Department of Dermatology, Nagoya University School of Medicine, Nagoya, Japan. ymuro@tsuru.med.nagoya-u.ac.jp
authors.forename: Y
authors.initials: Y
authors.lastname: Muro
authors.forename: N
authors.initials: N
authors.lastname: Azuma
authors.forename: H
authors.initials: H
authors.lastname: Onouchi
authors.forename: M
authors.initials: M
authors.lastname: Kunimatsu
authors.forename: Y
authors.initials: Y
authors.lastname: Tomita
authors.forename: M
authors.initials: M
authors.lastname: Sasaki
authors.forename: K
authors.initials: K
authors.lastname: Sugimoto
mesh_terms: D000595:Amino Acid Sequence; D001323:Autoantibodies / Q000097:blood / Q000378:metabolism; D001324:Autoantigens / Q000737:chemistry*; D002503:Centromere / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D000076247:Centromere Protein A; D002868:Chromosomal Proteins, Non-Histone / Q000737:chemistry* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D018604:Epitope Mapping; D000939:Epitopes / Q000737:chemistry*; D004926:Escherichia coli / Q000235:genetics; D006657:Histones / Q000737:chemistry*; D006801:Humans; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014764:Viral Proteins / Q000737:chemistry / Q000378:metabolism
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; C000619700:CENPA protein, human; D000076247:Centromere Protein A; D002868:Chromosomal Proteins, Non-Histone; D000939:Epitopes; D006657:Histones; D010446:Peptide Fragments; D011994:Recombinant Proteins; D014764:Viral Proteins