Petersdorf EW, Bengtsson M, Horowitz MM, et al. HLA-DQ Heterodimers in Hematopoietic-Cell Transplantation. Blood. 2022; (doi: 10.1182/blood.2022015860).
The risk of autoimmune disease relapse following hematopoietic-cell transplantation can be influenced by molecules generated by cis- and trans-dimerization of human leukocyte antigen (HLA)-DQα/DQß chains. This study confirmed the HLA-DQ heterodimer as a functional model of the transplantation barrier that can lower relapse risk for future patients. The researchers defined heterodimers in 5,164 HLA-matched and 520 HLA-DQ-mismatched patients and their transplant donors based on crystallographic criteria. Group 1 (G1) heterodimers were defined as any DQA1*02/03/04/05/06α matched with any DQB1*02/03/04ß, while group 2 (G2) heterodimers were DQA1*01α matched with any DQB1*05/06ß. Relapse risk was substantially elevated in G1G2 and G2G2 versus G1G1 HLA-matched patients with malignant disease, with increasing risk associated with higher numbers of G2 molecules. Matching or mismatching for G2 boosted the risk of relapse in HLA-DQ-mismatched transplantation for malignant diseases. G2 also reduced disease-free survival following HLA-matched and HLA-DQ-mismatched transplantation.