RT Journal Article
SR Electronic
T1 Autoantibodies to the Rpp25 Component of the Th/To Complex are the Most Common Antibodies in Patients with Systemic Sclerosis without Antibodies Detectable by Widely Available Commercial Tests
JF The Journal of Rheumatology
JO J Rheumatol
FD The Journal of Rheumatology
SP 1334
OP 1343
DO 10.3899/jrheum.131450
VO 41
IS 7
A1 Michael Mahler
A1 Minoru Satoh
A1 Marie Hudson
A1 Murray Baron
A1 Jason Y.F. Chan
A1 Edward K.L. Chan
A1 James Wick
A1 Marvin J. Fritzler
A1 and the Canadian Scleroderma Research Group
YR 2014
UL http://www.jrheum.org/content/41/7/1334.abstract
AB Objective. Antinuclear antibodies (ANA) occur in up to 95% of patients with systemic sclerosis (SSc). In most, SSc-associated antibodies are detected (i.e., centromere, topoisomerase I, RNA polymerase III, PM/Scl, Ro52/TRIM21, and U1RNP). Ribonuclease P protein subunit p25, (Rpp25) is an autoantigenic component of the Th/To complex. The contribution of anti-Th/To and anti-Rpp25 antibodies to ANA positivity in patients with SSc remains unknown. Methods. Sera from 873 patients with SSc were tested for ANA, and SSc-associated antibodies were measured. Samples without antibodies to extractable nuclear antigens (ENA; n = 53, ANA+/ENA−), were analyzed by immunoprecipitation (IP) and metabolically labeled proteins and for anti-Rpp25 antibodies (n = 50) by a chemiluminescent immunoassay (CLIA) and Rpp25 ELISA. Results. Anti-Th/To antibodies occurred in 19/53 (36%), as determined by IP, and were the most common autoantibody in ANA+/ENA− SSc. Of those samples, 50/53 were available for additional testing by CLIA and ELISA. Anti-Rpp25 antibodies were detected in 12 (24% CLIA) or 10 (20% ELISA) of 50 patients. Receiver-operating characteristic curve analysis showed similar discrimination between Th/To IP-positive (n = 19) and -negative samples (n = 31) by CLIA and ELISA (area under the curve 0.90 vs 0.87; p = 0.6691). The positive percent agreement between IP and CLIA or ELISA was 12/19 (63.2%, 95% CI 38.4–83.7%) or 10/19 (52.6%, 95% CI 73.3–94.2%), respectively. Negative percent agreement was 100% for both assays. Conclusion. Autoantibodies to the Th/To autoantigen are important in patients with SSc who have been considered negative for SSc-specific or SSc-associated antibodies by widely available commercial assays. Rpp25 can be considered a major target of anti-Th/To antibodies. Assays detecting anti-Th/To and anti-Rpp25 antibodies may be important in SSc.