Anti-fibrillarin antibody in African American patients with systemic sclerosis: immunogenetics, clinical features, and survival analysis

J Rheumatol. 2011 Aug;38(8):1622-30. doi: 10.3899/jrheum.110071. Epub 2011 May 15.

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).

Conclusion: 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Antibodies, Antinuclear / genetics*
  • Antibodies, Antinuclear / immunology*
  • Autoantibodies / genetics*
  • Autoantibodies / immunology*
  • Black or African American / genetics*
  • Chromosomal Proteins, Non-Histone / genetics
  • Chromosomal Proteins, Non-Histone / immunology*
  • Female
  • Gene Frequency
  • HLA-DRB1 Chains / immunology
  • Histocompatibility Antigens Class II / genetics
  • Histocompatibility Antigens Class II / immunology
  • Humans
  • Immunogenetics / methods
  • Male
  • Middle Aged
  • Scleroderma, Systemic / genetics
  • Scleroderma, Systemic / immunology*
  • Scleroderma, Systemic / pathology
  • Scleroderma, Systemic / physiopathology
  • Survival Analysis

Substances

  • Antibodies, Antinuclear
  • Autoantibodies
  • Chromosomal Proteins, Non-Histone
  • HLA-DRB1 Chains
  • HLA-DRB1*08:04 antigen
  • Histocompatibility Antigens Class II
  • fibrillarin