Distinct scleroderma autoantibody profiles stratify patients for cancer risk at scleroderma onset and during the disease course.

We examined whether an array of scleroderma autoantibodies associates with risk of cancer and could be useful tools for risk stratification.Scleroderma cancer cases and scleroderma controls without cancer from Johns Hopkins and University of Pittsburgh Scleroderma Centers were studied. Sera were assayed by Lineblot and ELISA for autoantibodies against centromere, topoisomerase 1, RNA polymerase III (POLR3), PM/Scl, Th/To, NOR90, U3RNP, Ku, Ro52, U1RNP, and RNPC3. Logistic regression models were constructed to examine whether distinct autoantibodies associated with overall cancer at any time and cancer-associated scleroderma (cancer occurring ±3 years of scleroderma onset). The effects of having >1 autoantibody on cancer were further examined using random forest analysis.676 cases and 687 controls were studied. After adjusting for relevant covariates, anti-POLR3 (OR 1.47, 95%CI 1.03-2.11) and monospecific anti-Ro52 (OR 2.19, 95%CI 1.29-3.74) associated with an increased overall cancer risk, whereas anti-centromere (OR 0.69, 95%CI 0.51-0.93) and anti-U1RNP (OR 0.63, 95%CI 0.43-0.93) associated with lower risk. When examining risk of cancer-associated scleroderma, these immune responses remained associated with increased or decreased risk: anti-POLR3 (OR 2.28, 95%CI 1.33-3.91), monospecific anti-Ro52 (OR 2.58, 95%CI 1.05-6.30), anti-centromere (OR 0.39, 95%CI 0.20-0.74), and anti-U1RNP (OR 0.32, 95%CI 0.11-0.93). Anti-Ro52 plus anti-U1RNP or anti-Th/To was associated with decreased cancer risk compared to anti-Ro52 alone.These data suggest that 5 distinct scleroderma immune responses, alone or in combination, may be useful tools to stratify scleroderma patients' cancer risk. Further study examining cancer risk in autoantibody subgroups relative to the general population is warranted.This article is protected by copyright. All rights reserved.

Citation

Ji Soo Kim, Adrianne Woods, Laura Gutierrez-Alamillo, Maureen Laffoon, Fredrick M Wigley, Laura K Hummers, Antony Rosen, Scott Zeger, Robyn T Domsic, Livia Casciola-Rosen, Ami A Shah. Distinct scleroderma autoantibody profiles stratify patients for cancer risk at scleroderma onset and during the disease course. Arthritis & rheumatology (Hoboken, N.J.). 2023 Jul 24

PMID: 37488962

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