Liver graft injury caused by de novo donor-specific HLA antibodies in pediatric liver transplant recipients with low, moderate, and high immunologic risk

T‐cell infiltrate intensity is associated with delayed response to treatment in late acute cellular rejection in pediatric liver transplant recipients

“…We also did not find convincing histologic evidence of antibody‐mediated rejection or de novo AIH in DR biopsies based on histologic assessment by a blinded pathologist (Table 3 ) , although this lack of association is likely hindered by small sample size and relatively short duration of follow‐up (median 4.5 years). The association of de novo DSA positivity with rejection risk is well documented, with current evidence suggesting that DSA are a marker of inadequate immunosuppression rather than truly pathogenic 11,18,39–42 . In our study, the concurrent findings of increased CD8 + lymphocyte infiltrates in individuals with concurrent DSA‐ and autoantibody‐positivity raises the interesting possibility that inflammation associated with rejection may release allo‐ and auto‐antigens from the inflamed liver to further sensitize the recipient 43,44 .…”

“…The association of de novo DSA positivity with rejection risk is well documented, with current evidence suggesting that DSA are a marker of inadequate immunosuppression rather than truly pathogenic. 11,18,[39][40][41][42] In our study, the concurrent findings of increased CD8 + lymphocyte infiltrates in individuals with concurrent DSA-and autoantibody-positivity raises the interesting possibility that inflammation associated with rejection may release allo-and auto-antigens from the inflamed liver to further sensitize the recipient. 43,44 Alternatively, the presence of DSA or autoantibodies may cause low-grade inflammation and chemokine production which drives T-cell tissue infiltration and/or release of antigens that primes CD8 + T cells.…”

Mapping children by ALT 4–5 years after liver transplant: Potential individual and population applications

“…2,17 An alternative objective metric might be DSA, specifically those with HLA Class II and DQ specificity. 16 Unfortunately, our center does not monitor alloantibody profiles so correlations could not be explored. Second, the small size of our single-center cohort limits quartile comparisons for rare outcomes, including chronic rejection, retransplantation, and liver-related procedural interventions.…”

“…Furthermore, we are now in the process of having a single pathologist reassess all available surveillance biopsies because the ongoing evolution of allograft biopsy scoring systems, particularly for fibrosis, makes it difficult to accurately compare the original assessments 2,17 . An alternative objective metric might be DSA, specifically those with HLA Class II and DQ specificity 16 . Unfortunately, our center does not monitor alloantibody profiles so correlations could not be explored.…”

“…Children with Yr 4-5 ALT values in the mid-to high-normal range may be more likely to have abnormal allografts or difficulty with medication adherence and benefit from the collection of additional risk-stratifying data. For instance, donor specific antibody (DSA) and MLVI are associated with allograft histopathology and unfavorable long-term clinical outcomes in pediatric patients 2,3,6,16. The presence of DSA with Class II and, in particular, DQ specificity or MLVI ≥2 may prompt consideration as to whether immunosuppression is adequate, discussion of adherence, and/or surveillance biopsy.…”