Characterization of antinucleolar antibody reactivity in patients with systemic sclerosis and their relatives

To study the prevalence and specificity of antinucleolar antibodies (ANoA) in patients with systemic sclerosis (SSc), their spouses, and their first-degree relatives, and to investigate whether SSc family members have greater frequency of ANoA than expected.

The sera of 58 SSc probands, 4 first-degree relatives with SSc, 215 first-degree relatives without SSc, and 24 spouses were screened for ANoA by indirect immunofluorescence (IF), and nucleolar antigens were characterized by immunoprecipitation (IP) of 35S methionine labeled K562 cell extracts. Sera from 118 randomly chosen family members without SSc were separately compared with 120 age and sex matched blood donor controls.

Antinucleolar reactivity was detected by IF in 25 patients with SSc (40.3%), in 33 non-SSc relatives (15.3%), and in 4 spouses (16.7%). Twenty-four sera had autoantibodies to defined nucleolar antigens by IP (seven Pm-Scl, ten RNA polymerase (pol) I, four U3 RNP, three Th RNP), and all were from patients with SSc (38.7%). No serum had more than one type of nucleolar-specific autoantibody. Four sera had autoantibodies to topoisomerase I (topo I) and RNA pol II, one of which also recognized RNA pol I and RNA pol III. Antinucleolar IF was significantly more common in the unaffected first-degree relatives of patients with SSc (18.1%) than in controls (8.3%; p < 0.05). A small number of sera from both relatives and controls recognized bands by IP, none of which was identified as a SSc-specific autoantigen.

Although antinucleolar reactivity is more common in the first-degree relatives of patients with SSc than controls, SSc associated ANoA are only present in patients with the disease, and appear to be mutually exclusive.