title: Clinical correlates of a subset of anti-CENP-A antibodies cross-reacting with FOXE3p53-62 in systemic sclerosis.
abstract: BACKGROUND
  In a subset of patients with limited cutaneous (lc) systemic sclerosis (SSc), anti-CENP-A antibodies (Ab) cross-react with a peptide (FOXE3p53-62) that presents striking homology with one of the two immunodominant epitopes of CENP-A (Ap17-30). We searched for clinical correlates of anti-FOXE3p53-62 Ab by measuring their levels along with those of Ab to Ap17-30 and to the second immunodominant epitope of CENP-A, namely Ap1-17.
  
  
  METHODS
  Serum samples were obtained from 121 patients with SSc, 46 patients with systemic lupus erythematosus (SLE) and 25 healthy blood donors (HBD). The reactivity of serum IgG to Ap1-17, Ap17-30 and FOXE3p53-62 was measured by ELISA. The corresponding anti-peptide Ab were affinity-purified from pooled SSc sera and used to establish standard curves for quantifying these Ab in patients and HBD. Receiver operating characteristics (ROC) analysis, comparing SSc patients who were positive for anti-CENP Ab (ACA+) to those who were negative, was used to find cut-off points for dichotomizing the anti-peptide Ab levels into positive and negative. Clinical records were reviewed to extract demographic data and information about organ involvement and disease activity.
  
  
  RESULTS
  Of 121 SSc sera, 75 were ACA+; 88.0% of these samples reacted with Ap1-17, 82.6% with Ap17-30 and 53.3% with FOXE3p53-62. Among the 46 ACA- SSc sera, 2.2% reacted with Ap1-17, 4.3% with Ap17-30 and 11% with FOXE3p53-62. The levels of these Ab were low in ACA-, SLE and HBD groups and not significantly different among them. When ACA+ SSc patients were divided into subgroups positive or negative for anti-FOXE3p53-62 Ab, the only variables that were significantly different between groups were the levels of anti-Ap17-30 Ab and disease activity index (DAI). There was a significant association between negativity for anti-FOXE3p53-62 Ab and active disease defined as either DAI ≥3 (Fisher exact test, P = 0.045) or less restrictive DAI≥2.5 (P = 0.009).
  
  
  CONCLUSIONS
  ACA+-Anti-FOXE3p53-62+Ab identifies a subgroup of patients with lcSSc who are less likely to develop active disease. In lc SSc patients at presentation, anti-FOXE3p53-62+ can be a marker with prognostic significance.
authors.forename: Federico
authors.initials: F
authors.lastname: Perosa
authors.forename: Elvira
authors.initials: E
authors.lastname: Favoino
authors.forename: Giovanna
authors.initials: G
authors.lastname: Cuomo
authors.forename: Liboria
authors.initials: L
authors.lastname: Digiglio
authors.forename: Franco
authors.initials: F
authors.lastname: Dammacco
authors.forename: Marcella
authors.initials: M
authors.lastname: Prete
authors.forename: Gabriele
authors.initials: G
authors.lastname: Valentini
authors.forename: Vito
authors.initials: V
authors.lastname: Racanelli
mesh_terms: D000328:Adult; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D015415:Biomarkers / Q000097:blood*; D000076247:Centromere Protein A; D002868:Chromosomal Proteins, Non-Histone / Q000276:immunology*; D003429:Cross Reactions; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D051858:Forkhead Transcription Factors / Q000276:immunology*; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology; D008297:Male; D012372:ROC Curve; D012189:Retrospective Studies; D045745:Scleroderma, Limited / Q000097:blood / Q000276:immunology* / Q000473:pathology; D012595:Scleroderma, Systemic / Q000097:blood / Q000276:immunology / Q000473:pathology
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D015415:Biomarkers; C000619700:CENPA protein, human; D000076247:Centromere Protein A; D002868:Chromosomal Proteins, Non-Histone; C404285:FOXE3 protein, human; D051858:Forkhead Transcription Factors; D016056:Immunodominant Epitopes