title: Donor-specific HLA-DQ antibodies may contribute to poor graft outcome after renal transplantation.
abstract: Increasing evidence suggests a detrimental effect of donor-specific antibodies directed against the human leukocyte antigen (HLA)-A, -B, and -DR loci on renal allograft outcomes. Limited data exist on the impact of de novo HLA-DQ antibodies. Over a 3-year period, we prospectively monitored 347 renal transplant recipients without pre-transplant donor-specific antibodies for their development de novo. After 26 months of follow-up, 62 patients developed donor-specific antibodies, of which 48 had a HLA-DQ antibody either alone (33 patients) or in combination with an HLA-A, -B, or -DR antibody (15 patients). Only 14 patients developed a donor-specific HLA-A, -B, or -DR antibody without a HLA-DQ antibody present. Acute rejection occurred in 21% of the HLA-DQ-only patients, insignificant when compared with 11% of patients without donor-specific antibodies. At the last follow-up, the mean serum creatinine and the fraction of patients with proteinuria were significantly higher in those that developed only HLA-DQ than those without antibodies. The 3-year graft survival was significantly worse when HLA-DQ antibodies were combined with non-DQ antibodies (52%) compared with HLA-DQ alone, non-DQ antibodies alone, or no antibodies (92-94%). Thus, our prospective monitoring study found that donor-specific HLA-DQ antibodies were the most common type detected and these antibodies may contribute to inferior graft outcomes. Ongoing surveillance is necessary to determine the long-term outcome of patients developing HLA-DQ donor-specific antibodies.
authors.affiliation: Department of Pharmacy, The Methodist Hospital, Houston, TX 77030, USA. JMDevos@tmhs.org
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: DeVos
authors.forename: A Osama
authors.initials: AO
authors.lastname: Gaber
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Knight
authors.forename: Geoffrey A
authors.initials: GA
authors.lastname: Land
authors.forename: Wadi N
authors.initials: WN
authors.lastname: Suki
authors.forename: Lillian W
authors.initials: LW
authors.lastname: Gaber
authors.forename: Samir J
authors.initials: SJ
authors.lastname: Patel
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D003404:Creatinine / Q000097:blood; D051799:Delayed Graft Function / Q000097:blood / Q000276:immunology; D005260:Female; D006084:Graft Rejection / Q000097:blood / Q000276:immunology / Q000517:prevention & control; D006085:Graft Survival; D015234:HLA-A Antigens / Q000276:immunology; D015235:HLA-B Antigens / Q000276:immunology; D006683:HLA-DQ Antigens / Q000276:immunology*; D006684:HLA-DR Antigens / Q000276:immunology; D006648:Histocompatibility; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007518:Isoantibodies / Q000097:blood*; D053208:Kaplan-Meier Estimate; D016030:Kidney Transplantation / Q000009:adverse effects / Q000276:immunology* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D015166:Monitoring, Immunologic; D011446:Prospective Studies; D011507:Proteinuria / Q000097:blood / Q000276:immunology; D012189:Retrospective Studies; D013781:Texas; D013997:Time Factors; D014019:Tissue Donors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; D007166:Immunosuppressive Agents; D007518:Isoantibodies; D003404:Creatinine