Background/Purpose: The idiopathic inflammatory myopathies (IIM) are a heterogenous group of autoimmune conditions. The presence of myositis-specific autoantibodies (MSAs) and myositis-associated autoantibodies (MAAs) in patients are important for diagnosis and prognosis. The currently accepted gold standards for autoantibody testing are time consuming and difficult to perform. Commercial testing may offer a more cost-effective and time-efficient method for autoantibody testing. However, the relative performance characteristics of commercial testing methods are not well known. We sought to determine the relative performance characteristics of autoantibody (Abs) testing from a widely-used commercial lab compared to gold standard methodologies.

Methods: Laboratory testing by protein and RNA immunoprecipitation (IP) and IP-immunoblotting methods performed by the Oklahoma Medial Research Foundation (OMRF) was used as the gold standard for anti-Jo1, OJ, EJ, PL-7, PL-12, Mi-2, SRP, Ku, MDA5, P155, PM/Scl, and MJ autoantibodies. Testing by ELISA and confirmation by IP in the Mammen laboratory was used as the gold standard for anti-HMGCR autoantibodies. Immunoblotting results from Mammen and Greenberg labs were used as gold standards for the CN1A autoantibody. Commercial antibody testing was performed on archived samples by a commercial lab using laboratory developed ELISAs for HMGCR and CN1A assays and a laboratory developed line blot method for the remaining autoantibodies. Up to 10 adults and juveniles positive by gold standard testing for each autoantibody were selected to be evaluated in the commercial lab.

Results: Samples from 198 patients with diagnosed IIM were used, of which 137 were adult and 61 were juvenile.

Across those autoantibodies with more than 5 gold standard positive (GSP) test results, sensitivities were greater than 0.95 for Jo1 (0.96, 22 GSP), EJ (1.0, 6 GSP), PL-12 (1.0, 10 GSP), and Ku (1.0, 8 GSP), and > 0.85 for Mi-2 (0.89, 9 GSP), MDA-5 (0.95, 19 GSP), and SRP (0.88, 20 GSP). PM/Scl (0.75, 8 GSP), MJ (0.74, 19 GSP), HMGCR (0.7, 10 GSP), P155 (0.48, 23 GSP), CN1A (0.37, 21 GSP), OJ (0, GSP) exhibited sensitivities under 0.85.

Two autoantibodies had specificities under 0.95: SRP (0.88) and Mi-2 (0.89). All other autoantibodies tested had a specificity above 0.95.

Subgroup analysis by age showed differences in sensitivity greater than 0.2 between CN1A Abs in adult (0.83) and juvenile IIM (0.15) (p = 0.004) and in anti-HMGCR Abs in adult (0.4) and juvenile IIM (0.15) (p = 0.038).

Conclusion: Of the autoantibodies with at least 5 positive gold standard positive results, there was a large variation in the sensitivities among the Abs. Sample storage may have impacted commercial test sensitivity. However, the specificities were strong overall. Our results show that commercial testing can be used as a tool for initial autoantibody testing in myositis patients, but the gold standards still provide value for autoantibody groups with low sensitivities, including P155, CN1A, and OJ. Further research is needed to explain sensitivity differences between age groups.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/performance-of-commercial-autoantibody-testing-in-comparison-to-recognized-gold-standards-in-myositis-autoantibody-testing/