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Anti-Th/To antibodies, found in 3–5% of patients with systemic sclerosis (SSc), recognise a nucleolar 7–2/8–2 RNA-protein complex. They are associated with limited SSc (lSSc) with lung involvement and reduced survival comparing with anticentromere (ACA) (+) patients. However, clinical studies on anti-Th/To are limited due to poor availability of serological tests. The aim of our study is to compare the clinical manifestations of patients with two autoantibodies associated with lSSc: anti-Th/To and ACA.
216 Italian SSc patients, followed between 2006 and 2008, were studied. Sera were tested by immunofluorescence for antinuclear antibodies, counterimmunoelectrophoresis for anti-ENA (anti-topo I, PM-Scl, Ku, U1RNP and others), and ELISA for anti-RNA polymerase III. Available sera (negative for all these) were also tested by immunoprecipitation (IP, protein analyses by 35S-methionine labelled cells; RNA analyses by urea-PAGE and silver staining). Specificities of autoantibodies were verified using reference sera. Charts were reviewed for clinical information.
Out of 216 patients, 67 were ACA (+) and 81 were anti-topo I (+). Among the remaining 68 patients, 15 were anti-RNAP III positive. Sera from 12 anti-nucleolar staining positive samples were available for IP: anti-Th/To antibodies were found in 8 of 12 patients (67%). They were all negative for ACA, anti-RNAP III and anti-ENA. Clinical features of eight anti-Th/To patients were compared with 67 ACA (+) patients. All except one ACA (+) patient had lSSc. Anti-Th/To patients were younger (p=0.0046), with a predominant male distribution (p=0.004) versus ACA (+) group. In anti-Th/To group, alveolitis (p=0.04), pericarditis (p=0.028) and puffy hands (p=0.0004) were more frequently detected. Both groups had low Medsger cardiopulmonary index and excellent 10-year survival.
Anti-Th/To are common in anti-nucleolar antibody positive Italian SSc patients. Both anti-Th/To and ACA patients had lSSc with excellent prognosis. Although impairment of pulmonary function appears mild, anti-Th/To group has frequent alveolitis and pericarditis. Testing for anti-Th/To should help to subset SSc patients and to follow-up properly.
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