The immunodominant epitope of centromere-associated protein A displays homology with the transcription factor forkhead box E3 (FOXE3).
Some patients with systemic sclerosis express autoantibodies to centromere-associated protein A (CENP-A), but the exact CENP-A epitope is unknown and it is possible that another protein primes these antibodies. This study aimed to define the amino acids recognized by these antibodies and discover other proteins that may be targeted by or may prime them. Peptide Ap(17-30), the immunodominant epitope of CENP-A, was used to purify anti-CENP-A Ig from sera of 8 patients. Anti-Ap(17-30) Ig reacted dose-dependently with Ap(17-30). Panning a phage display peptide library with anti-Ap(17-30) IgG identified two overlapping motifs (m), pt1m and pt8m, permitting patients classification into subgroups based on their having antibodies for only pt1m, pt8m, or both. The pt1m matched residues 53-62 of forkhead box E3; this peptide (FOXE3p(53-62)) behaved similarly in binding and inhibition assays with anti-Ap(17-30) IgG and elicited anti-Ap(17-30) antibodies in mice. This study sets the ground for future investigations on a possible relationship between antibody specificity and clinical manifestations of systemic sclerosis, as well as on a possible role of FOXE3 in priming these antibodies.
Perosa
Federico
F
Department of Internal Medicine and Clinical Oncology (DIMO), University of Bari Medical School, Bari, Italy. f.perosa@dimo.uniba.it
Vicenti
Chiara
C
Racanelli
Vito
V
Leone
Patrizia
P
Valentini
Gabriele
G
Dammacco
Franco
F
D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000097:blood / Q000276:immunology; D000915:Antibody Affinity / Q000276:immunology; D000918:Antibody Specificity / Q000276:immunology; D001323:Autoantibodies / Q000097:blood / Q000276:immunology / Q000302:isolation & purification; D001324:Autoantigens / Q000737:chemistry / Q000276:immunology*; D002503:Centromere / Q000276:immunology; D000076247:Centromere Protein A; D002868:Chromosomal Proteins, Non-Histone / Q000737:chemistry / Q000276:immunology*; D003429:Cross Reactions / Q000276:immunology; D030562:Databases, Protein; D005260:Female; D051858:Forkhead Transcription Factors / Q000737:chemistry / Q000276:immunology*; D006367:HeLa Cells; D006801:Humans; D016056:Immunodominant Epitopes / Q000737:chemistry / Q000276:immunology*; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology / Q000302:isolation & purification; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D010446:Peptide Fragments / Q000276:immunology; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D012595:Scleroderma, Systemic / Q000276:immunology; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014611:Vaccination
D000906:Antibodies; D001323:Autoantibodies; D001324:Autoantigens; C000619700:CENPA protein, human; C000619701:Cenpa protein, mouse; D000076247:Centromere Protein A; D002868:Chromosomal Proteins, Non-Histone; C404285:FOXE3 protein, human; D051858:Forkhead Transcription Factors; D016056:Immunodominant Epitopes; D007074:Immunoglobulin G; D010446:Peptide Fragments; D019151:Peptide Library; D010455:Peptides