HLA-DQ heterodimers in hematopoietic cell transplantation.

Blood 2022 May 19

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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 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. © 2022 by The American Society of Hematology.

Citation

Effie W Petersdorf, Mats Bengtsson, Mary Horowitz, Caroline McKallor, Stephen R Spellman, Eric Spierings, Ted A Gooley, Phil Stevenson, International Histocompatibility Working Group in Hematopoietic Cell Transplantation. HLA-DQ heterodimers in hematopoietic cell transplantation. Blood. 2022 May 19;139(20):3009-3017