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*02/03/04/05/06α paired with any DQB1*02/03/04β. Group 2 (G2) heterodimers are DQA1*01α paired with any DQB1*05/06β. Multivariable models identified significantly higher relapse risk in G1G2 and G2G2 compared to G1G1 HLA-matched patients with malignant disease; risk increased with increasing numbers 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.