HLA-DQ heterodimers promote autoimmune disease vulnerability, although their effect on hematopoietic cell transplantation was uncertain. Therefore, for a study, researchers investigated whether HLA-DQ heterodimers impacted the outcome of HLA-matched and HLA-DQ–mismatched hematopoietic cell transplantation. 

Heterodimers were determined using well-established crystallographic criteria in the 5,164 HLA-matched and 520 HLA-DQ–mismatched patients and their transplant donors. Any DQA1*02/03/04/05/06 heterodimer associated with any DQB1*02/03/04 is a Group 1 (G1) heterodimer. DQA1*01 heterodimers were DQA1*01 linked with any DQB1*05/06 heterodimer. 

G1G2 and G2G2 HLA-matched patients with malignant illness had a considerably greater recurrence risk than G1G1 HLA-matched patients suffering from malignant disease, according to the multivariable models; the risk rose as the number of G2 molecules increased. Matching or mismatching for G2 enhanced the probability of recurrence in HLA-DQ–mismatched transplantation for malignant illnesses. After HLA-matched and HLA-DQ–mismatched transplantation, G2 decreased disease-free survival. An HLA-DQ heterodimer-based paradigm gave a functional characterization of the hematopoietic cell transplantation barrier and a way to reduce future patient risks.