Association Between Donor HLA-DQ Heterodimers Group and Graft Loss in Kidney Transplant Recipients.

Abstract

Background: Combinations of HLA-DQ α1 and β1 chains are restricted to specific groups: group 1 (G1), comprising DQA1*02/03/04/05/06 with DQB1*02/03/04, and group 2 (G2), comprising DQA1*01 with DQB1*05/06. A recently discovered role of HLA-DQ heterodimers in hematopoietic cell transplantation suggests poorer outcomes in patients carrying G2 heterodimers. However, the absence of a clear biological rationale has raised questions regarding the generalizability of this observation. Methods: To further evaluate this finding, we investigated the impact of the HLA-DQ group genotype in 821 kidney recipients by multivariate survival modeling. Results: = 0.01) increased risk of graft failure, suggesting a biological gradient of effect. In sensitivity analyses, these results were independent of the usual predictors of graft loss. Conclusions: The paradigm based on HLA-DQ heterodimers appears to be shared between hematopoietic and solid organ transplantation, strongly encouraging investigation into the underlying biological mechanisms.