Pediatric living-donor liver transplant (LDLT) recipients can often exhibit a reduction or cessation of immunosuppression (IS); over the long term, a high incidence of progressive graft fibrosis is of particular concern. We conducted a cross-sectional study to examine the effects of donor-specific anti-HLA antibody (DSA) and angiotensin II type-1 receptor antibody (anti-AT1R) on post-transplant graft fibrosis. Fifty-eight pediatric LDLT patients who underwent IS withdrawal and had a follow-up biopsy were studied. The patients were classified into two groups according to their pathological status: severe fibrosis (Group-SF) (Ishak score≥3) and mild fibrosis (Group-MF) (Ishak score≤2). We used LABScreen Single Antigen beads to detect DSA and ELISA to detect anti-AT1R. All patients except one did not develop DSA-Class I. The strength of DSA-DRB1 was significantly higher in Group-SF than in Group-MF (MFI 8889 vs. 477, p<0.001), which resulted in a significantly higher percentage of high-level DSA-DRB1 (MFI>5000) in Group-SF than in Group-MF (50% vs. 3%, p<0.001). The frequency of high-level anti-AT1R patients (>17.0 U/ml) was significantly higher in Group-SF than Group-MF (71% vs. 39%, p=0.03).
|total||DSA-Class I (MFI>5000)||DSA-Class II (MFI>5000)||DSA-DQB1 (MFI>5000)||DSA-DRB1 (MFI>5000)||DSA-DRB345 (MFI>5000)||Anti-AT1R (>17 U/ml)|
|Mild fibrosis (Ishak≤2)||41||1 (3%)*||18 (47%)*||16 (42%)*||1 (3%)*||6 (16%)*||16 (39%)|
|Severe fibrosis (Ishak≥3)||17||0**||10 (63%)**||6 (38%)**||8 (50%)**||2 (13%)**||12 (71%)|
When patients were categorized according to their DSA-DRB1 and anti-AT1R level, all patients with both high-level DSA-DRB1 and high-level anti-AT1R had developed severe fibrosis.
|DSA-DRB1>5000 / anti-AT1R>17||Mild fibrosis (n=38)||Severe fibrosis (n=16)|
|– / –||23 (92%)||2 (8%)|
|– / +||14 (70%)||6 (30%)|
|+ / –||1 (33%)||2 (67%)|
|+ / +||0||6 (100%)|
We concluded that assessing anti-AT1R along with DSA-DRB1 provide additional information, and both HLA and non-HLA immunity may be involved in graft fibrosis after IS withdrawal.
To cite this abstract in AMA style:Oe H, Uchida Y, Yoshizawa A, Hirao H, Taniguchi M, Maruya E, Maekawa T, Uemoto S, Terasaki P. Impact of Donor-Specific Anti-HLA and Anti-Angiotensin-II Type 1 Receptor Antibodies on Graft Fibrosis after Immunosuppression Withdrawal in Pediatric Liver Transplantation [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/impact-of-donor-specific-anti-hla-and-anti-angiotensin-ii-type-1-receptor-antibodies-on-graft-fibrosis-after-immunosuppression-withdrawal-in-pediatric-liver-transplantation/. Accessed February 21, 2020.
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