title: HLA-DR and -DQ eplet mismatches and transplant glomerulopathy: a nested case-control study.
abstract: We conducted a nested case-control study from a cohort of adult kidney transplant recipients to assess the risk of transplant glomerulopathy (TG) as a function of donor and recipient HLA-DR and -DQ incompatibility at the eplet level. Cases (n = 52) were defined as patients diagnosed with transplant glomerulopathy based on biopsies showing glomerular basement membrane duplication without immune complex deposition. Controls (n = 104) with a similar follow-up from transplantation were randomly selected from the remaining cohort. HLAMatchmaker was used to ascertain the number of DRB1/3/4/5, DQA1 and DQB1 related eplet mismatches (eplet load). Multivariable conditional logistic regression models demonstrated an increase in the odds of TG (odds ratios [OR] of 2.84 [95% confidence interval (CI): 1.03, 7.84] and 4.62 [95% CI: 1.51, 14.14]) in the presence of 27-43 and >43 HLA-DR + DQ related eplet mismatches versus <27 eplet mismatches, respectively. When the eplet load was modeled as a continuous variable, the OR for TG was 1.25 (95% CI: 1.04, 1.50) for every 10 additional HLA-DR + DQ eplet mismatches. Our study suggests that minimization of HLA-DR + DQ eplet mismatches may decrease the incidence of transplant glomerulopathy diagnosed by indication biopsies. The role of eplet immunogenicity/antigenicity as determinants of allograft outcomes requires further study.
authors.affiliation: Division of Nephrology and The Kidney Transplant Program, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada; Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada; Department of Medicine, Division of Nephrology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: R
authors.initials: R
authors.lastname: Sapir-Pichhadze
authors.forename: K
authors.initials: K
authors.lastname: Tinckam
authors.forename: K
authors.initials: K
authors.lastname: Quach
authors.forename: A G
authors.initials: AG
authors.lastname: Logan
authors.forename: A
authors.initials: A
authors.lastname: Laupacis
authors.forename: R
authors.initials: R
authors.lastname: John
authors.forename: J
authors.initials: J
authors.lastname: Beyene
authors.forename: S J
authors.initials: SJ
authors.lastname: Kim
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D015433:Glomerulonephritis, Membranous / Q000209:etiology* / Q000276:immunology; D006084:Graft Rejection / Q000175:diagnosis / Q000209:etiology; D006085:Graft Survival; D006683:HLA-DQ Antigens / Q000276:immunology*; D006684:HLA-DR Antigens / Q000276:immunology*; D006648:Histocompatibility / Q000276:immunology*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000276:immunology / Q000601:surgery*; D007677:Kidney Function Tests; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications; D011379:Prognosis; D012307:Risk Factors; D066027:Transplant Recipients; D014184:Transplantation, Homologous
chemical_list: D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens