title: De novo donor specific antibodies and patient outcomes in renal transplantation.
abstract: Single antigen identification of HLA antibodies is used to detect donor specific antibodies (DSAs). However, the impact of DSA elements such as class, relative strength, duration, and longitudinal effect on graft function and survival, remains unclear. Routine DSAs (LabScreen, One Lambda, Inc., Canoga Park, CA) and metabolic studies were performed at 1, 3, 6, 9, and 12 months post-transplant, and every 6 months for renal transplant recipients from 7/2007-7/2010 (n = 389). Biopsies were evaluated by updated Banff 2005 guidelines after two consecutive positive DSAs. Based on these tests, 25% of recipients developed de novo DSA. Those with DSA had increased acute rejection episodes (AR), higher creatinine (Scr), and worse graft survival. Three subgroups of these patients were identified based on duration: persistent DSA (> 1), isolated DSA, or no DSA. Persistent DSA patients were more likely to be African American, and have higher mean fluorescence intensity (MFI) and AR rates. Persistent DSA patients, with or without AR, had elevated Scr. Recipients with DQ-only DSA had higher rates of antibody mediated rejection (AMR). From this, we conclude that routine posttransplant DSA monitoring identifies recipients at risk for graft damage or loss. Persistent de novo DSAs correlated with inferior graft outcomes and AMR. With or without AR, DSA persistence was associated with worse outcomes, possibly warranting intervention. De novo DQ-DSA may be a biomarker for chronic damage and/or AMR, while an isolated DSA determination appears clinically insignificant.
authors: The Methodist Transplant Center, The Methodist Hospital & Research Institute, Houston, Texas, USA.
authors: J M
authors: JM
authors: DeVos
authors: S J
authors: SJ
authors: Patel
authors: K M
authors: KM
authors: Burns
authors: S
authors: S
authors: Dilioglou
authors: L W
authors: LW
authors: Gaber
authors: R J
authors: RJ
authors: Knight
authors: A O
authors: AO
authors: Gaber
authors: G A
authors: GA
authors: Land
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D016009:Chi-Square Distribution; D003404:Creatinine / Q000097:blood; D005260:Female; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control; D006085:Graft Survival; D006680:HLA Antigens / Q000276:immunology*; D006648:Histocompatibility / Q000187:drug effects; D006650:Histocompatibility Testing; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007518:Isoantibodies / Q000097:blood*; D053208:Kaplan-Meier Estimate; D016030:Kidney Transplantation / Q000009:adverse effects / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D015166:Monitoring, Immunologic; D016035:Pancreas Transplantation / Q000009:adverse effects / Q000276:immunology*; D012189:Retrospective Studies; D013781:Texas; D013997:Time Factors; D023001:Transplantation Tolerance; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D006680:HLA Antigens; D007166:Immunosuppressive Agents; D007518:Isoantibodies; D003404:Creatinine