Anti-centromere protein A antibodies in systemic sclerosis: Significance and origin

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• 作者：Federico Perosa^a ; ^{federico.perosa@uniba.it" class="auth_mail" title="E-mail the corresponding author} ; Marcella Prete^b ; Giuseppe Di Lernia^a ; Carmela Ostuni^c ; Elvira Favoino^a ; Gabriele Valentini^d
• 关键词：Systemic sclerosis ; Centromere protein A ; Antibody ; Forkhead box protein E3 ; Phage display peptide library ; Epitope ; Motif
• 刊名：Autoimmunity Reviews
• 出版年：2016
• 出版时间：January 2016
• 年：2016
• 卷：15
• 期：1
• 页码：102-109
• 全文大小：784 K

文摘

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.