Johns Hopkins University, Baltimore, Maryland.
University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
Arthritis Rheumatol. 2024 Jan;76(1):68-77. doi: 10.1002/art.42663. Epub 2023 Nov 27.
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 the Johns Hopkins Scleroderma Center and the University of Pittsburgh Scleroderma Center were studied. Sera were assayed by Lineblot and enzyme-linked immunosorbent assay (ELISA) for autoantibodies against centromere, topoisomerase 1, RNA polymerase (POLR) 3, PM/Scl, Th/To, NOR90, U3 RNP, 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 three years before and after scleroderma onset). The effects of having more than one autoantibody on cancer were further examined using random forest analysis.
A total of 676 cases and 687 controls were studied. After adjusting for relevant covariates, anti-POLR3 (odds ratio [OR] 1.47, 95% confidence interval [CI] 1.03-2.11) and monospecific anti-Ro52 (OR 2.19, 95% CI 1.29-3.74) were associated with an increased overall cancer risk, whereas anticentromere (OR 0.69, 95% CI 0.51-0.93) and anti-U1RNP (OR 0.63, 95% CI 0.43-0.93) were 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), anticentromere (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 with anti-Ro52 alone.
These data suggest that five distinct scleroderma immune responses, alone or in combination, may be useful tools to stratify the risk of cancer for scleroderma patients. Further study examining cancer risk in autoantibody subgroups relative to the general population is warranted.
我们研究了一组硬皮病自身抗体是否与癌症风险相关，并能否作为风险分层的有用工具。
我们研究了来自约翰霍普金斯硬皮病中心和匹兹堡大学硬皮病中心的癌症病例和无癌症的硬皮病对照。通过 Lineblot 和酶联免疫吸附试验（ELISA）检测针对着丝粒、拓扑异构酶 1、RNA 聚合酶（POLR）3、PM/Scl、Th/To、NOR90、U3 RNP、Ku、Ro52、U1RNP 和 RNPC3 的自身抗体。构建逻辑回归模型以检查是否存在不同的自身抗体与任何时候的整体癌症以及癌症相关的硬皮病（癌症发生在硬皮病发病前 3 年和后 3 年）相关。使用随机森林分析进一步检查了具有多种自身抗体对癌症的影响。
共研究了 676 例病例和 687 例对照。调整相关协变量后，抗-POLR3（比值比 [OR] 1.47，95%置信区间 [CI] 1.03-2.11）和单特异性抗-Ro52（OR 2.19，95% CI 1.29-3.74）与整体癌症风险增加相关，而抗着丝粒（OR 0.69，95% CI 0.51-0.93）和抗-U1RNP（OR 0.63，95% CI 0.43-0.93）与较低的风险相关。当检查癌症相关硬皮病的风险时，这些免疫反应仍然与增加或降低的风险相关：抗-POLR3（OR 2.28，95% CI 1.33-3.91）、单特异性抗-Ro52（OR 2.58，95% CI 1.05-6.30）、抗着丝粒（OR 0.39，95% CI 0.20-0.74）和抗-U1RNP（OR 0.32，95% CI 0.11-0.93）。与仅抗-Ro52 相比，抗-Ro52 加抗-U1RNP 或抗-Th/To 与癌症风险降低相关。
这些数据表明，五种不同的硬皮病免疫反应，单独或联合使用，可能是分层硬皮病患者癌症风险的有用工具。进一步研究在自身抗体亚组中检查癌症风险与一般人群相比是否存在差异是有必要的。
