title: Anti-fibrillarin antibody in African American patients with systemic sclerosis: immunogenetics, clinical features, and survival analysis.
abstract: OBJECTIVE
  Anti-U3-RNP, or anti-fibrillarin antibodies (AFA), are detected more frequently among African American (AA) patients with systemic sclerosis (SSc) compared to other ethnic groups and are associated with distinct clinical features. We examined the immunogenetic, clinical, and survival correlates of AFA in a large group of AA patients with SSc.
  
  
  METHODS
  Overall, 278 AA patients with SSc and 328 unaffected AA controls were enrolled from 3 North American cohorts. Clinical features, autoantibody profile, and HLA class II genotyping were determined. To compare clinical manifestations, relevant clinical features were adjusted for disease duration. Cox proportional hazards regression was used to determine the effect of AFA on survival.
  
  
  RESULTS
  Fifty (18.5%) AA patients had AFA. After Bonferroni correction, HLA-DRB1*08:04 was associated with AFA, compared to unaffected AA controls (OR 11.5, p < 0.0001) and AFA-negative SSc patients (OR 5.2, p = 0.0002). AFA-positive AA patients had younger age of disease onset, higher frequency of digital ulcers, diarrhea, pericarditis, higher Medsger perivascular and lower Medsger lung severity indices (p = 0.004, p = 0.014, p = 0.019, p = 0.092, p = 0.006, and p = 0.016, respectively). After adjustment for age at enrollment, AFA-positive patients did not have different survival compared to patients without AFA (p = 0.493).
  
  
  CONCLUSIONS
  Our findings demonstrate strong association between AFA and HLA-DRB1*08:04 allele in AA patients with SSc. AA SSc patients with AFA had younger age of onset, higher frequency of digital ulcers, pericarditis and severe lower gastrointestinal involvement, but less severe lung involvement compared to AA patients without AFA. Presence of AFA did not change survival.
authors.affiliation: Division of Rheumatology and Immunogenetics, University of Texas Health Science Center at Houston, Houston, TX 77030, USA. roozbeh.sharif@uth.tmc.edu
authors.forename: Roozbeh
authors.initials: R
authors.lastname: Sharif
authors.forename: Marvin J
authors.initials: MJ
authors.lastname: Fritzler
authors.forename: Maureen D
authors.initials: MD
authors.lastname: Mayes
authors.forename: Emilio B
authors.initials: EB
authors.lastname: Gonzalez
authors.forename: Terry A
authors.initials: TA
authors.lastname: McNearney
authors.forename: Hilda
authors.initials: H
authors.lastname: Draeger
authors.forename: Murray
authors.initials: M
authors.lastname: Baron
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Furst
authors.forename: Dinesh K
authors.initials: DK
authors.lastname: Khanna
authors.forename: Deborah J
authors.initials: DJ
authors.lastname: del Junco
authors.forename: Jerry A
authors.initials: JA
authors.lastname: Molitor
authors.forename: Elena
authors.initials: E
authors.lastname: Schiopu
authors.forename: Kristine
authors.initials: K
authors.lastname: Phillips
authors.forename: James R
authors.initials: JR
authors.lastname: Seibold
authors.forename: Richard M
authors.initials: RM
authors.lastname: Silver
authors.forename: Robert W
authors.initials: RW
authors.lastname: Simms
authors.forename: Marilyn
authors.initials: M
authors.lastname: Perry
authors.forename: Carlos
authors.initials: C
authors.lastname: Rojo
authors.forename: Julio
authors.initials: J
authors.lastname: Charles
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Zhou
authors.forename: Sandeep K
authors.initials: SK
authors.lastname: Agarwal
authors.forename: John D
authors.initials: JD
authors.lastname: Reveille
authors.forename: Shervin
authors.initials: S
authors.lastname: Assassi
authors.forename: Frank C
authors.initials: FC
authors.lastname: Arnett
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics*; D000974:Antibodies, Antinuclear / Q000235:genetics* / Q000276:immunology*; D001323:Autoantibodies / Q000235:genetics* / Q000276:immunology*; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000276:immunology*; D005260:Female; D005787:Gene Frequency; D059811:HLA-DRB1 Chains / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology; D006801:Humans; D007125:Immunogenetics / Q000379:methods; D008297:Male; D008875:Middle Aged; D012595:Scleroderma, Systemic / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D016019:Survival Analysis
chemical_list: D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D002868:Chromosomal Proteins, Non-Histone; D059811:HLA-DRB1 Chains; C553508:HLA-DRB1*08:04 antigen; D000949:Histocompatibility Antigens Class II; C047458:fibrillarin