# The Presence of Non‐HLA Antibody With DSA Is Associated With Moderate to Severe T Cell‐Mediated Rejection in Liver Transplant Recipients

## TL;DR

Non-HLA antibodies, especially anti-AT1R and a panel of 18 antibodies, are linked to moderate to severe T-cell rejection in liver transplant patients, particularly when combined with HLA antibodies.

## Contribution

This study identifies non-HLA antibodies as significant predictors of T-cell-mediated rejection in liver transplants, suggesting their potential clinical relevance.

## Key findings

- Non-HLA antibodies, including anti-AT1R, are elevated in moderate-severe TCMR cases.
- A panel of 18 non-HLA antibodies is significantly associated with moderate-severe TCMR.
- The presence of DSA and non-HLA antibodies together increases the risk of moderate-severe TCMR.

## Abstract

Antibodies to donor HLA (DSA) and non‐HLA antigens are associated with detrimental outcomes in kidney, heart, and lung transplants. Such data are scarce in liver transplants (LTx). We aim to study the roles of DSA and non‐HLA antibodies in T‐cell‐mediated rejection (TCMR) of LTx.

Allograft biopsies (n = 103) from adult LTx recipients were studied. Biopsy‐paired serums were retrospectively tested for anti‐angiotensin II type 1 receptor (AT1R) and the Luminex panel of 60 non‐HLA Antibodies.

TCMR was detected in 59 of 103 (57.3%) biopsies. Twenty‐six biopsies were categorized as moderate‐severe (MS‐TCMR), 77 as negative‐mild (NM‐TCMR). DSA was positive in 95/103 (92.2%) cases and wasn't associated with MS‐TCMR. Anti‐AT1R antibodies were elevated in serum paired with MS‐TCMR vs. NM‐TCMR (18.8[15.2–40.0] vs. 13.0[10.0–21.5] U/ml, p < 0.01). Positive anti‐AT1R antibodies were associated with a higher incidence of MS‐TCMR (HR = 12.4[1.5–101.6], p = 0.02). A panel of 18 non‐HLA Abs was significantly associated with MS‐TCMR. The number of panel‐18 non‐HLA antibodies was higher with MS‐TCMR vs. NM‐TCMR (3[2–5] vs. 1[0–1], p < 0.001). The incidence of MS‐TCMR was higher in cases with panel‐18 non‐HLA antibodies ≥3 vs. <3 (HR = 19.6[6.0–64.8], p < 0.001). The frequency of MS‐TCMR was the highest when DSA, anti‐AT1R, and panel‐18 non‐HLA antibodies were all present.

Non‐HLA antibodies to AT1R or the Luminex panel are associated with MS‐TCMR in LTx biopsies. The incidence of MS‐TCMR is higher when non‐HLA antibodies are present concomitantly with DSA, indicating an additive effect. Further studies are warranted to investigate the utility of routinely monitoring DSA and non‐HLA antibodies in LTx recipients.