title: Anti-centromere protein A antibodies in systemic sclerosis: Significance and origin.
abstract: Systemic sclerosis (SSc) is systemic, autoimmune, connective tissue disorder characterized by vascular abnormalities, collagen deposition (fibrosis), and the production of autoantibodies to nuclear proteins. About 20%-40% of patients have antibodies to centromere protein (CENP)-A or -B. Despite the known association of anti-CENP antibodies with certain clinical features of SSc, the role of these antibodies in SSc physiopathology is still poorly understood. To better understand the clinical significance and origin of these antibodies, we and others have been studying the epitopic motifs (amino acid contact sites) on CENP-A with the aim of determining whether other proteins can prime or be targeted by them. Here, we review published and ongoing studies aimed at defining the fine specificity and origin of anti-CENP-A antibodies. We describe progress made in identifying the CENP-A epitopic motif amino acids, and the discovery of one of these motifs in forkhead box protein E3 (FOXE-3), a transcription factor previously studied only for its role in the development of lens fiber cells. Moreover, we discuss preliminary evidence for a possible role of FOXE-3 in SSc pathogenesis and for the association of different subsets of anti-CENP-A antibodies, heterogeneously expressed among SSc patients, with some clinical correlates.
authors.affiliation: Department of Biomedical Sciences and Human Oncology (DIMO), Section of Systemic Rheumatic and Autoimmune Diseases, University of Bari Medical School, Bari, Italy. Electronic address: federico.perosa@uniba.it.
authors.forename: Federico
authors.initials: F
authors.lastname: Perosa
authors.affiliation: Department of Biomedical Sciences and Human Oncology (DIMO), Section of Internal Medicine, University of Bari Medical School, Bari, Italy.
authors.forename: Marcella
authors.initials: M
authors.lastname: Prete
authors.affiliation: Department of Biomedical Sciences and Human Oncology (DIMO), Section of Systemic Rheumatic and Autoimmune Diseases, University of Bari Medical School, Bari, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Di Lernia
authors.affiliation: Department of Biomedical Sciences and Human Oncology (DIMO), Section of Clinical Oncology, University of Bari Medical School, Bari, Italy.
authors.forename: Carmela
authors.initials: C
authors.lastname: Ostuni
authors.affiliation: Department of Biomedical Sciences and Human Oncology (DIMO), Section of Systemic Rheumatic and Autoimmune Diseases, University of Bari Medical School, Bari, Italy.
authors.forename: Elvira
authors.initials: E
authors.lastname: Favoino
authors.affiliation: Department of Clinical and Experimental Internal Medicine "F. Magrassi, A. Lanzara", Rheumatology Section, Second University of Naples, Naples, Italy.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Valentini
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology*; D000918:Antibody Specificity; D001324:Autoantigens / Q000276:immunology*; D000076247:Centromere Protein A; D002868:Chromosomal Proteins, Non-Histone / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D006801:Humans; D019151:Peptide Library; D012595:Scleroderma, Systemic / Q000276:immunology*
chemical_list: D000906:Antibodies; D001324:Autoantigens; C000619700:CENPA protein, human; D000076247:Centromere Protein A; D002868:Chromosomal Proteins, Non-Histone; D000939:Epitopes; D019151:Peptide Library
keywords: Antibody; Centromere protein A; Epitope; Forkhead box protein E3; Motif; Phage display peptide library; Systemic sclerosis