Donor-specific HLA Antibodies Are Associated With Late Allograft Dysfunction After Pediatric Liver Transplantation. Issue 7 (July 2015)

• Record Type: Journal Article
• Authors: Wozniak, Laura J.; Hickey, Michelle J.; Venick, Robert S.; Vargas, Jorge H.; Farmer, Douglas G.; Busuttil, Ronald W.; McDiarmid, Sue V.; Reed, Elaine F.
• Is Part Of: Transplantation. Volume 99:Issue 7(2015)
• Publication Date: 2015-07
• Subjects: Transplantation of organs, tissues, etc -- Periodicals; Transplantation immunology -- Periodicals; 617.95
• DOI: 10.1097/TP.0000000000000796
• Languages: English
• ISSNs: 0041-1337

Abstract

Abstract : Background: The role of donor-specific HLA antibodies (DSA) after pediatric liver transplantation (LTx) is not clearly established. We completed a cross-sectional study to characterize DSA in long-term survivors of pediatric LTx and assess the impact of C1q-binding DSA on allograft outcomes. Methods: Serum samples were collected at routine clinic visits from 50 pediatric LTx recipients classified into 3 clinical phenotypes: nontolerant (n = 18) with de novo autoimmune hepatitis (DAIH) and/or late acute cellular rejection (ACR); stable (n = 25) on maintenance tacrolimus; operationally tolerant (n = 7). Samples were blinded, and antibody detection was performed using Luminex single antigen class I and II beads. Patients with positive DSA were tested for C1q-binding DSA. Results: DSA were detected in 54% (n = 27) of the patients, with the majority directed at HLA class II antigens (DR, 41%; DQ, 53%). Patients with DSA were younger at the time of LTx ( P = 0.016) and time of study ( P = 0.024). Mean aspartate aminotransferase, alanine aminotransferase, total bilirubin, and gamma glutamyl transferase were higher in DSA-positive patients, though did not reach statistical significance. Nontolerant patients were significantly more likely to have DQ DSA (61%) compared to stable (20%) and tolerant (29%) patients ( P = 0.021). The nontolerant phenotype was associated with DSA and C1q-binding DSA, with odds ratios of 13 ( P = 0.015) and 8.6 ( P = 0.006), respectively. The presence of DQ DSA was associated with DAIH and late ACR, with odds ratios of 12.5 ( P = 0.004) and 10.8 ( P = 0.006), respectively. Conclusions: Allograft dysfunction is not always evident in patients with DSA, but DQ DSA are strongly associated with DAIH, late ACR, and chronic rejection. Abstract : In a cross-sectional study of 50 pediatric liver transplant recipients, the authors report on the strong correlation of anti-HLA antibodies donor-specific antibodies, especially class II, anti- DQ and C1q-binding, on non-tolerant with de-novo autoimmune hepatitis, late acute cellular rejection and chronic rejection.