HLA-DQ heterodimers in hematopoietic cell transplantation. Blood 2022 May 19;139(20):3009-3017
Date
03/11/2022Pubmed ID
35271697Pubmed Central ID
PMC9121842DOI
10.1182/blood.2022015860Scopus ID
2-s2.0-85130706095 (requires institutional sign-in at Scopus site) 13 CitationsAbstract
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.
Author List
Petersdorf EW, Bengtsson M, Horowitz M, McKallor C, Spellman SR, Spierings E, Gooley TA, Stevenson P, International Histocompatibility Working Group in Hematopoietic Cell TransplantationAuthor
Mary M. Horowitz MD, MS Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AllelesHLA-DQ Antigens
HLA-DQ beta-Chains
Hematopoietic Stem Cell Transplantation
Humans
Recurrence
Tissue Donors