2071 Ceribelli,etal:Anti-Th/Toantibodies Personal non-commercial use only. The Journal of Rheumatology Copyright © 2010. All rights reserved. Anti-Th/To Are Common Antinucleolar Autoantibodies in Italian Patients with Scleroderma ANGELACERIBELLI,ILARIACAVAZZANA,FRANCOFRANCESCHINI,PAOLOAIRÒ,ANGELATINCANI, ROBERTOCATTANEO,BRADA.PAULEY,EDWARDK.L.CHAN,andMINORUSATOH ABSTRACT. 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.WeexaminedtheautoantibodyprofilesandclinicalmanifestationsinacohortofItalian 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 immuno- fluorescence), antitopoisomerase I (topo I; by counterimmunoelectrophoresis), and anti-RNA poly- merase 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-U3RNPwas found. In comparison with ACA-positive patients, anti-Th/To-positive patients were younger (p = 0.0046) and more common- ly 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 fre- quent pericarditis and ILD, although impairment of pulmonary function appeared mild. (First ReleaseAugust 1 2010; J Rheumatol 2010;37:2071–5; doi:10.3899/jrheum.100316) KeyIndexingTerms: ANTI-Th/ToANTIBODIES ANTINUCLEOLARANTIBODIES ANTICENTROMEREANTIBODIES SYSTEMIC SCLEROSIS RNA-IMMUNOPRECIPITATION FromtheRheumatologyUnit,A.O.SpedaliCivili,UniversitàdegliStudi, Brescia,Italy;andDepartmentofOralBiologyandDepartmentof Medicine,UniversityofFlorida,Gainesville,Florida,USA. A.Ceribelli,MD;I.Cavazzana,MD;F.Franceschini,MD;P.Airò,MD; A.Tincani,MD;R.Cattaneo,MD,RheumatologyUnit,A.O.Spedali CivilidiBrescia,UniversitàdegliStudidiBrescia;B.A.Pauley,BSc; E.K.L.Chan,PhD,DepartmentofOralBiology,UniversityofFlorida; M.Satoh,MD,PhD,DepartmentofMedicine,UniversityofFlorida. AddresscorrespondencetoDr.A.Ceribelli,DepartmentofOralBiology, CollegeofDentistry,UniversityofFlorida,POBox100424,Gainesville, FL32610-0424.E-mail:dott.ceribelli@libero.it AcceptedforpublicationMay13,2010. Scleroderma (systemic sclerosis, SSc) is a chronic autoim- mune connective tissue disease characterized by vascular changes, fibrosis, and presence of autoantibodies, such as anticentromere (ACA), antitopoisomerase I (topo I), and anti-RNA polymerase III (RNAPIII) antibodies 1 . Patients with scleroderma can be classified into subsets associated with unique clinical features (cutaneous and visceral involvement,rapidityofdiseaseprogression,andprognosis) and specific autoantibodies. In particular, 2 major subsets, the limited (lcSSc) and the diffuse (dcSSc) cutaneous vari- ants,areclinicallyrecognized:dcSScisfrequentlyassociat- edwithanti-topoIoranti-RNAPIIIantibodies,whilelcSSc isassociatedwithACAoranti-Th/Toantibodies 1,2 . In immunofluorescence antinuclear antibody (ANA) screening,anti-topoIandanti-RNAPIIIshownuclearstain- ing in fine speckled-homogeneous (topo I) or coarse speck- led(RNAPIII)patterns.ELISAandothermethodsarewide- ly used in clinical practice to confirm these specificities 3 . ACAthatappearasadiscretespecklednuclearstainingpat- terncanbeassessedbyascreeningANAtestaloneinmost cases. In contrast, some SSc patients’ sera show a pure or dominant nucleolar staining pattern. Anti-Th/To, fibrillarin (U3RNP), and PM-Scl are the common specificities of nucleolar stain-positive SSc sera. However, these autoanti- bodies can be identified mainly by immunoprecipitation (IP),whichisnotwidelyusedinclinicallaboratories.Thus, clinical information available on these antibodies is based onstudiesfromafewinstitutions,despitedatasuggestinga significant effect of ethnicity on autoantibody profile and clinical features 1 . We examined the clinical and immunological features www.jrheum.org Downloaded on November 27, 2021 from