@article {Mahlerjrheum.131450, author = {Michael Mahler and Minoru Satoh and Marie Hudson and Murray Baron and Jason Y.F. Chan and Edward K.L. Chan and James Wick and Marvin J. Fritzler}, title = {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}, elocation-id = {jrheum.131450}, year = {2014}, doi = {10.3899/jrheum.131450}, publisher = {The Journal of Rheumatology}, abstract = {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{\textendash}), 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{\textendash} 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{\textendash}83.7\%) or 10/19 (52.6\%, 95\% CI 73.3{\textendash}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.}, issn = {0315-162X}, URL = {https://www.jrheum.org/content/early/2014/06/11/jrheum.131450}, eprint = {https://www.jrheum.org/content/early/2014/06/11/jrheum.131450.full.pdf}, journal = {The Journal of Rheumatology} }