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Antibodies to RNA Polymerase III in Systemic Sclerosis Detected by ELISA

MITTERMAYER SANTIAGO, MURRAY BARON, MARIE HUDSON, RUFUS W. BURLINGAME, for the Canadian Scleroderma Research Group, and MARVIN J. FRITZLER

ABSTRACT.

Objective.
To determine serological and clinical variables associated with anti-RNA polymerase III (RNAP-III) antibodies in patients with systemic sclerosis (SSc) using a new ELISA method.

Methods. Sera from 242 patients with SSc were collected from 14 Canadian clinics. Control sera were from 287 blood donors, and 42 patients with infectious disease, 30 with rheumatoid arthritis (RA), and 30 with systemic lupus erythematosus (SLE). Antibodies to RNAP-III were detected by an ELISA kit and antibodies to other cellular antigens were identified by indirect immunofluorescence (IIF) on HEp-2 cell substrate, line immunoassay, immunoprecipitation of recombinant protein, and addressable laser bead immunoassay (ALBIA).

Results. Anti-RNAP-III antibodies were detected in 47/242 (19.4%) SSc sera, 0% RA and SLE sera, 1/287 blood donor sera, and 2/42 infectious disease sera. Diffuse disease (59.5%) was more common than limited disease (36.1%) in the anti-RNAP-III-positive patients (p = 0.006) and there was an association between the presence of anti-RNAP-III and kidney and joint/tendon involvement, but there was no association with a nucleolar IIF pattern, lung involvement, or other clinical indicators. There was a negative association between the presence of anti-RNAP-III antibodies and anticentromere by IIF (p = 0.00004) and anti-Scl-70 by ALBIA (p = 0.0005) and line immunoassay (p = 0.003), suggesting a virtually exclusive presence of these antibodies in SSc.

Conclusion. Anti-RNAP-III autoantibodies were found in nearly 20% of SSc patients but in less than 1% of controls, thus detection of this antibody is a useful marker to help diagnose SSc. As well, this antibody has prognostic utility, since it is associated with scleroderma renal crisis and the diffuse cutaneous form of SSc. (First Release June 15 2007; J Rheumatol 2007;34:1528-34)

Key Indexing Terms:

AUTOANTIBODIES
SYSTEMIC SCLEROSIS
RNA POLYMERASE
ELISA


From the Serviço de Reumatologia do Hospital do Santa Izabel/Escola Bahiana de Medicina e Saúde Pública, Salvador, Brazil; Division of Rheumatology, Jewish General Hospital, McGill University, Montréal, Quebec, Canada; INOVA Diagnostics Inc., San Diego, California, USA; and the Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada.

Supported by grant 38034 from the Canadian Institutes of Health Research. Dr. Fritzler holds the Arthritis Society Research Chair at the University of Calgary. Funds from this endowment supported sabbatical leave of Dr. Santiago. Dr. Santiago also received a scholarship from CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior). R. Burlingame is an employee of INOVA Diagnostics Inc., San Diego, CA. Dr. Fritzler is a paid consultant to ImmunoConcepts Inc., Sacramento, CA.

M. Santiago, MD, Serviço de Reumatologia do Hospital do Santa Izabel/Escola Bahiana de Medicina e Saúde Pública; M. Baron, MD, Chief, Division of Rheumatology,; M. Hudson, MD, MPH, Division of Rheumatology, SMBD–Jewish General Hospital, McGill University; R.W. Burlingame, PhD, Senior Scientist, INOVA Diagnostics Inc.; M.J. Fritzler, PhD, MD, Faculty of Medicine, University of Calgary. The Canadian Scleroderma Research Group: M. Abu-Hakima, Calgary, Alberta; M. Bell, Toronto, Ontario; A.P. Docherty, Moncton, New Brunswick; M. Hudson, Montréal, Quebec; N. Jones, Edmonton, Alberta; M. Khraishi, St. John's, Newfoundland; S. Leclercq, Calgary, Alberta; J. Markland, Saskatoon, Saskatchewan; J-P. Mathieu, Montréal, Quebec; J. Pope, London, Ontario; D. Robinson, Winnipeg, Manitoba; D. Smith, Ottawa, Ontario; E. Sutton, Halifax, Nova Scotia.

Address reprint requests to Dr. M.J. Fritzler, Faculty of Medicine, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta T2N 4N1, Canada. E-mail: fritzler@ucalgary.ca

Accepted for publication March 12, 2007.




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