title: HLA-DQ Mismatches and Rejection in Kidney Transplant Recipients.
abstract: The current allocation algorithm for deceased donor kidney transplantation takes into consideration HLA mismatches at the ABDR loci but not HLA mismatches at other loci, including HLA-DQ. However, the independent effects of incompatibilities for the closely linked HLA-DQ antigens in the context of HLA-DR antigen matched and mismatched allografts are uncertain. We aimed to determine the effect of HLA-DQ mismatches on renal allograft outcomes.
  
  
  
  Using data from the Australia and New Zealand Dialysis and Transplant Registry, we examined the association between HLA-DQ mismatches and acute rejections in primary live and deceased donor kidney transplant recipients between 2004 and 2012 using adjusted Cox regression models.
  
  
  
  Of the 788 recipients followed for a median of 2.8 years (resulting in 2891 person-years), 321 (40.7%) and 467 (59.3%) received zero and one or two HLA-DQ mismatched kidneys, respectively. Compared with recipients who have received zero HLA-DQ mismatched kidneys, those who have received one or two HLA-DQ mismatched kidneys experienced greater numbers of any rejection (50 of 321 versus 117 of 467; P<0.01), late rejections (occurring >6 months post-transplant; 8 of 321 versus 27 of 467; P=0.03), and antibody-mediated rejections (AMRs; 12 of 321 versus 38 of 467; P=0.01). Compared with recipients of zero HLA-DQ mismatched kidneys, the adjusted hazard ratios for any and late rejections in recipients who had received one or two HLA-DQ mismatched kidneys were 1.54 (95% confidence interval [95% CI], 1.08 to 2.19) and 2.85 (95% CI, 1.05 to 7.75), respectively. HLA-DR was an effect modifier between HLA-DQ mismatches and AMR (P value for interaction =0.02), such that the association between HLA-DQ mismatches and AMR was statistically significant in those who have received one or two HLA-DR mismatched kidneys, with adjusted hazard ratio of 2.50 (95% CI, 1.05 to 5.94).
  
  
  
  HLA-DQ mismatches are associated with acute rejection, independent of HLA-ABDR mismatches and initial immunosuppression. Clinicians should be aware of the potential importance of HLA-DQ matching in the assessment of immunologic risk in kidney transplant recipients.
authors.affiliation: Department of Renal Medicine, Sir Charles Gairdner Hospital, Perth, Western Australia, Australia.|Australia and New Zealand Dialysis and Transplant Registry, Adelaide, South Australia, Australia.
authors.forename: Wai H
authors.initials: WH
authors.lastname: Lim
authors.affiliation: Centre for Transplant and Renal Research, Westmead Hospital, Sydney, New South Wales, Australia.
authors.forename: Jeremy R
authors.initials: JR
authors.lastname: Chapman
authors.affiliation: Central and Northern Adelaide Renal and Transplantation Services, Royal Adelaide Hospital, Adelaide, South Australia, Australia.
authors.forename: Patrick T
authors.initials: PT
authors.lastname: Coates
authors.affiliation: Centre for Kidney Research, The Children's Hospital at Westmead, Sydney School of Public Health, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Joshua R
authors.initials: JR
authors.lastname: Lewis
authors.affiliation: Australia and New Zealand Dialysis and Transplant Registry, Adelaide, South Australia, Australia.|Central and Northern Adelaide Renal and Transplantation Services, Royal Adelaide Hospital, Adelaide, South Australia, Australia.
authors.forename: Graeme R
authors.initials: GR
authors.lastname: Russ
authors.affiliation: New South Wales Transplantation and Immunogenetic Services, Australian Red Cross Service, Sydney, New South Wales, Australia; and.
authors.forename: Narelle
authors.initials: N
authors.lastname: Watson
authors.affiliation: Transplantation Services, Australian Red Cross Services, Melbourne, Victoria, Australia.
authors.forename: Rhonda
authors.initials: R
authors.lastname: Holdsworth
authors.affiliation: Australia and New Zealand Dialysis and Transplant Registry, Adelaide, South Australia, Australia.|Centre for Transplant and Renal Research, Westmead Hospital, Sydney, New South Wales, Australia.|Centre for Kidney Research, The Children's Hospital at Westmead, Sydney School of Public Health, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Germaine
authors.initials: G
authors.lastname: Wong
mesh_terms: D000328:Adult; D064591:Allografts / Q000276:immunology* / Q000502:physiology; D000906:Antibodies / Q000276:immunology; D001315:Australia / Q000453:epidemiology; D005260:Female; D006084:Graft Rejection / Q000453:epidemiology* / Q000276:immunology*; D006085:Graft Survival; D006683:HLA-DQ Antigens / Q000276:immunology*; D006801:Humans; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D009520:New Zealand / Q000453:epidemiology; D013997:Time Factors
chemical_list: D000906:Antibodies; D006683:HLA-DQ Antigens
keywords: Allografts; Epidemiology and outcomes; HLA Antigens; HLA-matching; Humans; acute allograft rejection; immunosuppression; kidney transplantation; registry; renal dialysis