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De Novo DQA/DQB Donor Specific Antibodies (DSA) Is Associated with Allograft Dysfunction in Pediatric Liver Transplantation (LT).

U. Ekong, L. Bow, R. Morotti, J. Gannon, P. Valentino, P. Yoo, M. Rodriguez-Davalos, S. Emre.

Yale New Haven Transplantation Center, New Haven.

Meeting: 2016 American Transplant Congress

Abstract number: D198

Keywords: Alloantibodies, HLA antibodies, Liver transplantation, Pediatric

Session Information

Date: Tuesday, June 14, 2016

Session Name: Poster Session D: Pediatric Liver Transplantation

Session Time: 6:00pm-7:00pm

 Presentation Time: 6:00pm-7:00pm

Location: Halls C&D

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Antibody mediated rejection following LT is thought to be uncommon. Studies suggest HLA Ab that bind C1q may be deleterious to the TX allograft, & HLA & non-HLA mechanisms may underlie fibrosis after LT.

Aim: To describe the presence of DSA HLA, C1q DSA, & angiotensin II type 1 receptor (AT1R) Ab in pediatric LT recipients & correlate their presence with allograft dysfunction (AD) & fibrosis.

Methods: pre-LT sera was available for DSA, AT1R Ab & C1q DSA measurements in 32, 23 & 14 patients respectively & post LT during AD blood obtained for DSA, AT1R Ab & C1q DSA in 20, 20 & 12 patients respectively. HLA Ab measured using luminex SAB kits (MFI>3000 +), C1q (MFI>1000 +), AT1R Ab by EIA (One Lambda). Biopsies (bx) were available in 14 patients. Liver fibrosis scored as previously described1.

Tests of association included Fisher's exact test & Wilcoxon Mann Whitney Test. Pre/post LT AT1R analyzed using Wilcoxon Signed Rank Sum Test.

Results: Mean age at LT:5.0 ± 5.8 years; mean time from LT at blood draw & liver bx:3.3 ± 2.9 & 3.0 ± 2.7 years respectively. Biliary atresia (BA) was the leading indication for LT (50%) & 50% of LT were live donor. 1 patient had Class I DSA pre-LT (3.13%). No patient had Class II DSA pre-LT. 8 patients (40%) had Class II DSA post LT, 7 of 8 MFI >10,000, 6 of 8 + C1q binding. Predominant DSA was DQA/DQB. No patient had Class I DSA post-LT. AT1R Ab seen pre & post-LT in 60% & 75% of patients respectively. Acute rejection (AR) diagnosed in 50% of bx. Mild to moderate fibrosis in 13 of 14 bx, severe fibrosis in 1 bx.

Post-LT AT1R Ab correlated with pre-LT diagnosis of BA (p=0.001). Young age at LT associated with a likelihood of having AT1R Ab post LT (p=0.06). No correlation between Class II DSA, C1q & LFT's or between Class II DSA, C1q, AT1R Ab & portal, sinusoidal, central fibrosis. Evolution of DSA & C1q with plasmapheresis & IVIG Rx shown below.

Conclusion: an active humoral response occurs de novo in a cohort of pediatric LT recipients with AD. AT1R Ab commonly seen pre & post LT however AT1R Ab & DSA did not correlate with fibrosis.

1 Venturi et al AJT2012:12, 2896-2996.

CITATION INFORMATION: Ekong U, Bow L, Morotti R, Gannon J, Valentino P, Yoo P, Rodriguez-Davalos M, Emre S. De Novo DQA/DQB Donor Specific Antibodies (DSA) Is Associated with Allograft Dysfunction in Pediatric Liver Transplantation (LT). Am J Transplant. 2016;16 (suppl 3).

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To cite this abstract in AMA style:

Ekong U, Bow L, Morotti R, Gannon J, Valentino P, Yoo P, Rodriguez-Davalos M, Emre S. De Novo DQA/DQB Donor Specific Antibodies (DSA) Is Associated with Allograft Dysfunction in Pediatric Liver Transplantation (LT). [abstract]. Am J Transplant. 2016; 16 (suppl 3). https://atcmeetingabstracts.com/abstract/de-novo-dqadqb-donor-specific-antibodies-dsa-is-associated-with-allograft-dysfunction-in-pediatric-liver-transplantation-lt/. Accessed March 8, 2021.

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