title: Clinical correlates of CENP-A and CENP-B antibodies in a large cohort of patients with systemic sclerosis.
abstract: OBJECTIVE
  To study the clinical phenotypes of centromeric proteins (CENP)-A- and CENP-B-positive patients with systemic sclerosis (SSc) and to compare them to anticentromere antibody (ACA)-positive and negative SSc patients.
  
  
  METHODS
  Sera samples were collected from 802 patients with SSc enrolled in a multicenter cohort study. Antibodies to CENP-A and B were detected by ELISA, and ACA by indirect immunofluorescence. Associations with clinical and other serological manifestations of SSc were investigated.
  
  
  RESULTS
  CENP-A antibodies were detected in 276 (34%), CENP-B in 286 (36%), and ACA in 279 (35%) patients. Patients having ACA, CENP-A, and/or CENP-B resembled each other and differed from the remainder of the cohort in the following respects: older chronologically and at disease onset; more commonly women; more likely to have limited disease and lower skin scores; less likely to have finger ulcers, digital tuft resorption, or finger contractures; more likely to have pulmonary hypertension; less likely to have interstitial lung disease, scleroderma renal crisis, inflammatory arthritis, and inflammatory myositis; and having lower overall disease severity. CENP-A and/or B status was predictive of the extent of skin involvement over time. Patients with limited disease who were CENP-A-negative at baseline were more likely to progress to diffuse disease compared to CENP-A-positive patients (OR 2.55, 95% CI 1.37, 4.85, p = 0.004).
  
  
  CONCLUSIONS
  Clinical immunology laboratories are increasingly using high-throughput ELISA tests for CENP antibodies, with or without ACA detected by indirect immunofluorescence. The phenotype of CENP-A and/or B-positive patients is generally similar to that associated with ACA.
authors.affiliation: Jewish General Hospital, Room A-725, 3755 Cote Ste Catherine Road, Montreal, Quebec H3T 1E2, Canada. marie.hudson@mcgill.ca
authors.forename: Marie
authors.initials: M
authors.lastname: Hudson
authors.forename: Michael
authors.initials: M
authors.lastname: Mahler
authors.forename: Janet
authors.initials: J
authors.lastname: Pope
authors.forename: Daniel
authors.initials: D
authors.lastname: You
authors.forename: Solene
authors.initials: S
authors.lastname: Tatibouet
authors.forename: Russell
authors.initials: R
authors.lastname: Steele
authors.forename: Murray
authors.initials: M
authors.lastname: Baron
authors.forename: Marvin
authors.initials: M
authors.lastname: Fritzler
mesh_terms: D000328:Adult; D000368:Aged; D000974:Antibodies, Antinuclear / Q000096:biosynthesis / Q000097:blood; D001323:Autoantibodies / Q000096:biosynthesis / Q000097:blood*; D001324:Autoantigens / Q000276:immunology*; D000076247:Centromere Protein A; D051936:Centromere Protein B / Q000276:immunology*; D002868:Chromosomal Proteins, Non-Histone / Q000276:immunology*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012595:Scleroderma, Systemic / Q000097:blood / Q000453:epidemiology* / Q000276:immunology*; D012871:Skin Diseases / Q000453:epidemiology / Q000276:immunology / Q000473:pathology
chemical_list: D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D001324:Autoantigens; C000619700:CENPA protein, human; C497926:CENPB protein, human; D000076247:Centromere Protein A; D051936:Centromere Protein B; D002868:Chromosomal Proteins, Non-Histone; C538950:anticentromere antibody