%0 Journal Article %A Michael Mahler %A Minoru Satoh %A Marie Hudson %A Murray Baron %A Jason Y.F. Chan %A Edward K.L. Chan %A James Wick %A Marvin J. Fritzler %A and the Canadian Scleroderma Research Group %T 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 %D 2014 %R 10.3899/jrheum.131450 %J The Journal of Rheumatology %P 1334-1343 %V 41 %N 7 %X 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. %U https://www.jrheum.org/content/jrheum/41/7/1334.full.pdf