Impact of Donor-Specific Anti-HLA and Anti-Angiotensin-II Type 1 Receptor Antibodies on Graft Fibrosis after Immunosuppression Withdrawal in Pediatric Liver Transplantation
Surgery, Kyoto University, Kyoto, Japan
Transfusion Medicine and Cell Therapy, Kyoto University Hospital, Kyoto, Japan
Paul I. Terasaki Foundation Laboratory, Los Angeles, CA
Meeting: 2013 American Transplant Congress
Abstract number: 551
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%) |
| P=0.51 | P=0.31 | P=0.75 | P<0.001 | p=0.82 | p=0.03 |
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 May 14, 2025.« Back to 2013 American Transplant Congress