Anti-RNA polymerases and other autoantibody specificities in systemic sclerosis

Abstract

Sera from 735 patients with systemic sclerosis were classified according to antinuclear antibody (ANA) pattern as follows: centromere (25%), homogeneous (26%), fine speckled (21%), fine speckled with nucleolar (14%), coarse speckled (7%), nucleolar only (3%) and cytoplasmic only (3%). Immunoprecipitations using 35S-labelled HeLa cell antigen extract were performed using sera from 374 of these patients to detect the systemic sclerosis-specific antibodies to RNA polymerases I and III. The sera were selected to represent each ANA group, but focused on those giving fine speckled nucleoplasmic staining (with or without nucleolar staining) where all 86 sera positive for these antibodies were concentrated. Immunoprecipitates from a further 93 sera from patients with ANA-positive autoimmune diseases other than systemic sclerosis did not precipitate RNA polymerases. In addition, all sera were tested for antibodies to the extractable nuclear antigens topoisomerase I, nRNP, Ro, La and PM-Scl. Sera positive for antibodies to these antigens gave clear correlations with ANA patterns but, of the examples tested, none contained antibodies precipitating RNA polymerase I or III. Thus, sera containing antibodies to RNA polymerases I and III were exclusive of both anticentromere and anti-topoisomerase I, and formed a major serological subgroup (11.7%). Clinically, 77% were patients with diffuse cutaneous disease reflected by higher skin scores and a significantly higher incidence of renal involvement (33%) than patients with antibodies to topoisomerase I (3%).

Relationship between change in skin score and disease outcome in diffuse cutaneous systemic sclerosis: Application of a latent linear trajectory model

“…This is consistent with the recognition that a significant number of patients with lcSSc have anti-topo I autoantibodies. Nevertheless, both of these antibodies have previously been reported to identify cases associated with poor outcome and renal or lung involvement (20,21). …”

Current Views on the Heterogeneity of Renal Involvements in Patients With Systemic Sclerosis

“…Антитела к РНК-полимеразе-3 (при определении с использованием ELISA) высоко специфичны для диф-О б з о р фузной формы ССД, и у 24-33% пациентов, позитивных по данным антителам, развивается СПК [35,36].…”

IgG from patients with systemic sclerosis bind to DNA antitopoisomerase 1 in normal human fibroblasts extracts

“…Many autoantibodies have been detected in the serum of SSc patients, including disease specifi c such as anticentromere antibodies, associated with limited cutaneous SSc (Moroi et al 1980;Steen et al 1988); antitopoisomerase 1 antibodies associated with diffuse SSc (Steen et al 1988;Weiner et al 1988); and anti-RNA-polymerase III antibodies which are associated with renal involvement (Bunn et al 1998). In addition, non specifi c autoantibodies have also been identifi ed in the serum of SSc patients, including antifi brillin 1 (Tan et al 1999), antiendothelial cell antibodies (AECA) (Ihn et al 2000;Sgonc et al 2000;Garcia de la Pena-Lefebvre et al 2004), and antifi broblast antibodies (AFA) (Brentnall et al 1982;Alderuccio et al 1989; Tamby et al Chizzolini et al 2002;Ronda et al 2002;Zhou et al 2005;Baroni et al 2006).…”