The association of antinuclear antibodies with organ involvement and survival in systemic sclerosis

Rheumatology (Oxford). 2003 Apr;42(4):534-40. doi: 10.1093/rheumatology/keg170.

Abstract

Objectives: To study the frequency and specificity of antinuclear antibodies (ANA) and their association with internal organ involvement and survival in systemic sclerosis (SSc).

Methods: Sera from 276 SSc patients were analysed by an indirect immunofluorescence (IIF) technique with HEp-2 cells as a substrate to categorize centromeric (ACA), nucleolar, speckled and homogeneous nuclear IIF patterns. Specific ANA were determined as follows: anti-DNA topoisomerase I (anti-topo I) by double immunodiffusion, anti-U1 RNP by passive haemagglutination, anti-RNA polymerase I, II and III (anti-RNAP) and anti-histone (AHA) antibodies by enzyme immunoassays. During the follow-up of 7.0+/-4.5 (mean+/-S.D.) yr the occurrence of clinical manifestations and internal organ involvement was registered.

Results: ANA were present in 84% of the patients. The most common patterns of the IIF were speckled (41%), homogeneous (25%), nucleolar (24%) and centromeric (18%). A nucleolar pattern was associated with pulmonary fibrosis (P < 0.01) and cardiomegaly (P < 0.05). ACA were related to organic vasculopathy (P < 0.05) and renal involvement (P < 0.01), but not to pulmonary fibrosis (P < 0.01). Anti-topo I were present in 9.4%, anti-U1 RNP in 21%, anti-RNAP in 22% and AHA in 16% of the patients. Pulmonary involvement was more common in patients with anti-topo I (P < 0.05), whereas AHA-positive patients were characterized by cardiac (P < 0.05), pulmonary (P < 0.05) and renal (P < 0.05) involvement. A nucleolar IIF pattern and AHA were both associated with a decreased survival [relative risk of death 1.71 (P < 0.05) and 2.36 (P < 0.01), respectively].

Conclusions: AHA and a nucleolar HEp-2 cell pattern may indicate critical organ involvement and predict a reduced survival in SSc patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibodies, Antinuclear / blood*
  • Biomarkers / blood
  • Centromere / immunology
  • Female
  • Fluorescent Antibody Technique, Indirect
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Nucleolus Organizer Region / immunology
  • Prognosis
  • Proportional Hazards Models
  • Scleroderma, Systemic / immunology*
  • Scleroderma, Systemic / pathology
  • Survival Analysis

Substances

  • Antibodies, Antinuclear
  • Biomarkers