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

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

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.

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].

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