Session Title: B cells in Human and Animal Arthritis
Session Type: Abstract Submissions (ACR)
Antinuclear antibodies (ANA) play an important role in the diagnosis of systemic sclerosis (SSc) being present in about 80-90% of the patients. In the majority of ANA positive SSc patients, SSc-specific and SSc-associated antibodies can be detected (i.e. antibodies to centromere, Scl-70, RNA Pol-III, PM/Scl, Ro52/TRIM21 and U1RNP). However, in a significant portion of ANA positive SSc patients, no fine specificities can be detected when conventional diagnostic protocols are used. Several studies demonstrated limited sensitivity for the detection of autoantibodies (especially anti-nucleolar antibodies) using solid phase screening assays in SSc patients. Recently, it was found that anti-Rpp25 antibodies are an important autoantigenic component of the Th/To complex. However, it remains unknown how much anti-Th/To and anti-Rpp25 antibodies contribute to ANA positivity in SSc patients. Consequently, the present study aimed to define the prevalence of autoantibodies to Rpp25 in SSc patients without other SSc-specific or SSc-associated antibodies.
Sera from 874 Canadian SSc patients were tested for ANA and various SSc-specific and SSc-associated antibodies including antibodies to common extractable nuclear antigens (ENA) and to those contained in a SSc line immunoassay (Euroimmun, Germany). Samples without those antibodies (n=54, later referred to as ANA+/ENA-) were analyzed by immunoprecipiation (IP) analysis of proteins and RNAs and for anti-Rpp25 antibodies (n=51) by a chemiluminescent immunoassay (CIA, QUANTA Flash, INOVA Diagnostics, US) and Rpp25 ELISA (University of Florida, US).
Anti-Th/To antibodies were the most common antibody in ANA+/ENA-negative SSc patients; being found in 18/54 (26%) of the patients as determined by IP. A total of 51 of these samples were available for additional testing by CIA and ELISA. Anti-Rpp25 antibodies were detected in 12 (23.5%, CIA) or 10 (19.6%, ELISA) of 51 patients when using the recently established cut-off values. ROC analysis showed similar discrimination between Th/To IP positive (n=18) and negative samples (n=33) by CIA and ELISA (AUC 0.89 vs. 0.86; p=0.7491). The positive percent agreements between IP and CIA or ELISA were 12/18 (66.7%, 95% Confidence interval 41.0-86.7%) or 10/18 (56.7%, 95% CI 30.8-78.5%), respectively. Negative percent agreements were 100% for both assays (95% CI 89.4-100.0%).
Autoantibodies to the Th/To autoantigen are important in SSc patients who have been considered to be negative for SSc-specific or SSc-associated antibodies by widely available commercial assays. Rpp25 has been confirmed as a major target of these anti-Th/To antibodies. Diagnostic assays for the detection of anti-Th/To and anti-Rpp25 antibodies hold promise to improve the diagnosis and management of SSc. Rpp25 might also help to improve solid phase screening assays for the detection of autoantibodies in SSc patients.
Inova Diagnostics, Inc.,
J. Y. F. Chan,
E. K. L. Chan,
M. J. Fritzler,
Inova Diagnostics, Inc.,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/autoantibodies-to-the-thto-complex-are-the-most-common-antibodies-in-systemic-sclerosis-ssc-patients-without-other-autoantibodies/