HLA-DQ heterodimers in hematopoietic cell transplantation

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 DQA1*02/03/04/05/06a paired with any DQB1*02/03/040. Group 2 (G2) heterodimers are DQA1*01a paired with any DQB1*05/060. 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.

Automated summary

HLA-DQ heterodimers influence susceptibility to autoimmune diseases, but their role in hematopoietic cell transplantation is unknown. This study found that the presence of G2 heterodimers increased the risk of relapse in HLA-matched and HLA-DQ-mismatched patients undergoing transplantation, and the risk increased with a higher number of G2 molecules.