Baltimore, Maryland.
Trans Am Clin Climatol Assoc. 2022;132:34-43.
The striking association of specific autoantibodies with distinct disease phenotypes and trajectories in human autoimmune rheumatic diseases provides a powerful opportunity to interrogate disease mechanism. In scleroderma, a subgroup of patients with autoantibodies to POLR3 have coincident onset of cancer and scleroderma. The majority of these patients have genetic changes (somatic mutations and loss of heterozygosity) in the POLR3A gene in their matched cancers, coupled with immune responses directed against the mutated and wild type autoantigen. In some individuals with scleroderma or dermatomyositis where specific immune responses mark a high risk of emergent cancer, cancer does not emerge. Such patients have a broader immune response that targets additional autoantigens, suggesting that the breadth and magnitude of the immune response regulates cancer, and that the rheumatic diseases provide a unique window into natural immunoediting of cancer in humans. This has implications for prediction and therapy in both autoimmunity and cancer.
在人类自身免疫性风湿病中，特定自身抗体与不同疾病表型和病程之间的显著关联，为探究疾病机制提供了一个强大的机会。在硬皮病中，一组自身抗体针对 POLR3 的患者同时出现癌症和硬皮病。这些患者的大多数在其匹配的癌症中都存在 POLR3A 基因的遗传改变（体细胞突变和杂合性丢失），并伴有针对突变和野生型自身抗原的免疫反应。在一些硬皮病或皮肌炎患者中，特定的免疫反应标志着发生癌症的高风险，但癌症并未出现。这些患者有更广泛的免疫反应，针对其他自身抗原，这表明免疫反应的广度和强度调节着癌症，而这些风湿性疾病为人类癌症的自然免疫编辑提供了一个独特的窗口。这对自身免疫和癌症的预测和治疗都有影响。
