Preformed and de novo DSA are associated with T‐cell–mediated rejection in pediatric liver transplant recipients requiring clinically indicated liver biopsy

Abstract

Despite growing interest about the impact of donor‐specific HLA antibodies (DSA) in LT limited data are available for pediatric recipients. Our aim was to perform a retrospective single‐center chart review of children (0‐16 years) having undergone LT between January 1, 2005 and December 31, 2017, to characterize DSA, to identify factors associated with the development of de novo DSA, and to analyze potential associations with the diagnosis of TCMR. Information on patient‐ and donor‐characteristics and LB reports were analyzed retrospectively. Serum obtained before LT and at LB was analyzed for presence of recipient HLA antibody using Luminex® technology. MFI > 1000 was considered positive. In 63 pediatric LT recipients with a median follow‐up of 72 months, the overall prevalence of de novo DSA was 60.3%. Most were directed against class II antigens (33/38, 86.8%). Preformed DSA were present in 30% of patients. Twenty‐eight (28/63) patients (44.4%) presented at least one episode of TCMR, mostly (12/28, 43%) moderate (Banff 6‐7). De novo DSA were significantly more frequent in patients with TCMR than in patients without (75% vs 48.6%, P = .03), and patients with preformed and de novo DSA had a significantly higher rate of TCMR than patients without any DSA (66.7% vs 20%, P = .02). Neither preformed DSA nor de novo DSA were associated with frequency or severity of TCMR. Recipients with lower weight at LT developed de novo DSA more frequently (P = .04). De novo DSA were highly prevalent in pediatric LT recipients. Although associated with the development of TCMR, they did not appear to impact the frequency or severity of TCMR or graft survival. Instead, de novo DSA may suggest a state of insufficient IS.

Post-transplant donor-specific anti-HLA antibodies with a higher mean fluorescence intensity are associated with graft fibrosis in pediatric living donor liver transplantation

“…Of these, 37 (47.2%) showed a maximum DSA-MFI > 20,000 ( 20 ). In addition, de novo DSAs were detected in 60.3%–63% of pediatric LT patients ( 23 , 24 ). In LDLT, 32% of pediatric patients were found to have class II DSA post-transplantation ( 25 ).…”

Antibody-mediated rejection of the liver allograft: An update and a clinico-pathological perspective

“…Additionally, severe TCMR in itself may be associated with elevated DSAs and C4d positivity, as can severe plasma cell-rich rejection. [27][28][29] Conventional immunosuppressive treatment of these cases may decrease C4d positivity and DSA titre, thus making the formal diagnosis of AMR more difficult to establish.…”

Antibody-Mediated Rejection and Recurrent Primary Disease: Two Main Obstacles in Abdominal Kidney, Liver, and Pancreas Transplants

“…With the minimization of immunosuppressants, it is often observed that liver transplant recipients also developed dnDSA in serum, with the tendency of this belonging to class II rather than class I [25,32]. In terms of the relation between dnDSA and TCMR, the prevalence of dnDSA was clearly higher in recipients who experienced TCMR, albeit without a correlation with frequency and severity [33]. With regard to the effects of dnDSA development, the correlation between dnDSA and more severe fibrosis was observed [34,35].…”