Objective: Patients with scleroderma (systemic sclerosis; SSc) can be classified into subsets based on autoantibody profile and clinical features. Specificities such as anti-Th/To and anti-fibrillarin (U3RNP) are detectable mainly by immunoprecipitation (IP), which is not widely used in clinical laboratories. We examined the autoantibody profiles and clinical manifestations in a cohort of Italian patients with SSc, focusing on anti-Th/To and anticentromere (ACA) antibodies, associated with limited cutaneous SSc (lcSSc).
Methods: Sera from 216 consecutive patients with SSc were tested for ACA (by indirect immunofluorescence), antitopoisomerase I (topo I; by counterimmunoelectrophoresis), and anti-RNA polymerase III (RNAPIII; by ELISA). Forty-one sera negative for these specificities were tested by IP analysis of proteins ((35)S-methionine labeled K562 cell extract) and RNA (silver staining).
Results: Among 216 SSc patients analyzed, anti-topo I, ACA, and anti-RNAPIII were detected in 38% (81/216), 31% (67/216) and 7% (15/216), respectively. Among 41 sera negative for ACA, anti-topo I, and anti-RNAPIII and which were tested by IP, 14 were nucleolar stain-positive. Eight out of 14 (57%) showed anti-Th/To reactivity, but no anti-U3RNP was found. In comparison with ACA-positive patients, anti-Th/To-positive patients were younger (p = 0.0046) and more commonly were male (p = 0.0006). All 8 anti-Th/To-positive and all but one ACA-positive patients had lcSSc. Interstitial lung disease (ILD) and pericarditis were more frequent in anti-Th/To-positive patients.
Conclusion: Anti-Th/To are common in antinucleolar antibody-positive Italian patients with SSc. Anti-Th/To and ACA patients had lcSSc, with excellent prognosis. The anti-Th/To group had frequent pericarditis and ILD, although impairment of pulmonary function appeared mild.