Definition of HLA-DQ as a transplantation antigen

Abstract

Recent studies have demonstrated the importance of recipient HLA-DRB1 allele disparity in the development of acute graft-versus-host disease (GVHD) after unrelated donor marrow transplantation. The role of HLA-DQB1 allele disparity in this clinical setting is unknown. To elucidate the biological importance of HLA-DQB1, we conducted a retrospective analysis of 449 HLA-A, -B, and -DR serologically matched unrelated donor transplants. Molecular typing of HLA-DRB1 and HLA-DQB1 alleles revealed 335 DRB1 and DQB1 matched pairs; 41 DRB1 matched and DQB1 mismatched pairs; 48 DRB1 mismatched and DQB1 matched pairs; and 25 DRB1 and DQB1 mismatched pairs. The conditional probabilities of grades III-IV acute GVHD were 0.42, 0.61, 0.55, and 0.71, respectively. The relative risk of acute GVHD associated with a single locus HLA-DQB1 mismatch was 1.8 (1.1, 2.7; P = 0.01), and the risk associated with any HLA-DQB1 and/or HLA-DRB1 mismatch was 1.6 (1.2, 2.2; P = 0.003). These results provide evidence that HLA-DQ is a transplant antigen and suggest that evaluation of both HLA-DQB1 and HLA-DRB1 is necessary in selecting potential donors.

Figure 1

Conditional probability of grades III–IV acute GVHD was 0.42 for group 1 (DRB1 and DQB1 matched, n = 335), 0.61 for group 2 (DRB1 matched and DQB1 mismatched, n = 41), 0.55 for group 3 (DRB1 mismatched and DQB1 matched, n = 48), and 0.71 for group 4 (DRB1 and DQB1 mismatched, n = 25) by day 80 after transplantation. Data in parentheses denote the number of patients who developed grades III–IV acute GVHD.

Figure 2

Conditional probability of grades III–IV acute GVHD in transplants mismatched for HLA-DRB1 and/or HLA-DQB1 (groups 2, 3, and 4 combined defined as group 5) was 0.60.