Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA.
Department of Medicine, University of Washington, Seattle, WA.
Blood. 2022 May 19;139(20):3009-3017. doi: 10.1182/blood.2022015860.
HLA-DQ heterodimers increase the susceptibility to autoimmune diseases, but their role in hematopoietic cell transplantation is unknown. We tested the hypothesis that outcome after HLA-matched and HLA-DQ-mismatched hematopoietic cell transplantation is influenced by HLA-DQ heterodimers. Heterodimers were defined in 5164 HLA-matched and 520 HLA-DQ-mismatched patients and their transplant donors according to well-established crystallographic criteria. Group 1 (G1) heterodimers are any DQA102/03/04/05/06α paired with any DQB102/03/04β. Group 2 (G2) heterodimers are DQA101α paired with any DQB105/06β. Multivariable models identified significantly higher relapse risk in G1G2 and G2G2 compared with G1G1 HLA-matched patients with malignant disease; risk increased with an increasing number of G2 molecules. In HLA-DQ-mismatched transplantation for malignant diseases, matching or mismatching for G2 increased relapse risk. G2 lowered disease-free survival after both HLA-matched and HLA-DQ-mismatched transplantation. A paradigm based on HLA-DQ heterodimers provides a functional definition of the hematopoietic cell transplantation barrier and a means to lower risks for future patients.
HLA-DQ 异二聚体增加自身免疫性疾病的易感性，但它们在造血细胞移植中的作用尚不清楚。我们检验了这样一个假设，即 HLA 匹配和 HLA-DQ 错配造血细胞移植的结果受到 HLA-DQ 异二聚体的影响。根据既定的晶体学标准，在 5164 名 HLA 匹配和 520 名 HLA-DQ 错配的患者及其移植供体中定义了异二聚体。第 1 组（G1）异二聚体是任何 DQA102/03/04/05/06α与任何 DQB102/03/04β配对。第 2 组（G2）异二聚体是 DQA101α与任何 DQB105/06β配对。多变量模型确定，与恶性疾病 HLA 匹配的 G1G1 患者相比，G1G2 和 G2G2 患者的复发风险显著更高；随着 G2 分子数量的增加，风险增加。在 HLA-DQ 错配的恶性疾病移植中，G2 的匹配或不匹配增加了复发风险。G2 降低了 HLA 匹配和 HLA-DQ 错配移植后的无病生存。基于 HLA-DQ 异二聚体的范例为造血细胞移植屏障提供了功能定义，并为未来患者降低风险提供了一种手段。
