Novel insights into pretransplant allosensitization in heart transplant recipients in the contemporary era of immunosuppression and rejection surveillance

Abstract

SummarySolid-phase assays (SPA) have facilitated detection and definition of antibodies to human leukocyte antigens (HLA) and major histocompatibility complex class I chain-related antigen A (MICA). However, clinical consequences of pretransplant SPA results in heart transplantation have been studied insufficiently in the current era of immunosuppression and rejection surveillance. Pretransplant sera, panelreactive antibodies (PRA), pretransplant crossmatch, and clinical data were retrospectively analyzed in 264 adult heart transplant recipients. The specificity of HLA and MICA antibodies and C1q-binding activity of donor-specific antibodies (DSA) were defined using SPA. Pretransplant HLA antibodies were detected in 57 (22%) individuals, in 28 individuals (11%); these antibodies were DSA after transplant. Preformed DSA and elevated peak PRA were independent predictors of pathologic AMR, which occurred in 19 individuals (7%). The increasing number of DSA and the cumulative mean fluorescence intensity of DSA were associated with AMR. C1q-binding assay was a suboptimal predictor of AMR in our cohort. Pretransplant allosensitization and MICA antibodies were related neither to impaired graft survival nor to other adverse clinical events during a median follow-up of 39 months. Identification of preformed DSA by SPA, in addition to PRA monitoring, may predict AMR in the contemporary era of heart transplantation.

Post‐transplant survival in adult congenital heart disease patients as compared to dilated and ischemic cardiomyopathy patients; an analysis of the thoracic ISHLT registry

“…ACHD patients were more likely to have a PRA of >80%. A study by Svobodova et al 16 found that preformed DSA and elevated peak PRA were independent predictors of antibody‐mediated rejection. We however did not find an increased mortality due to rejection‐mediated causes, possibly due to the limitations of a registry analysis and missing data.…”

Significance of Anti-HLA Antibodies on Adult and Pediatric Heart Allograft Outcomes

“…In contrast, high titer DSA (>1:16) has been associated with complement-fixing reactivity ( 7 , 20 ) and has been used to determine unacceptable HLA antigens for sensitized candidates ( 5 ). DSA determination by SPA and elevated peak panel-reactive antibodies (PRA) were independent predictors of pAMR in an adult cohort of heart transplant recipients ( 21 ). In this study focusing on pretransplant samples, increasing numbers of DSAs and the mean cumulative MFI of DSAs were associated with risk of AMR, and the subset of C1q-reactive DSAs were less informative ( 21 ).…”

“…DSA determination by SPA and elevated peak panel-reactive antibodies (PRA) were independent predictors of pAMR in an adult cohort of heart transplant recipients ( 21 ). In this study focusing on pretransplant samples, increasing numbers of DSAs and the mean cumulative MFI of DSAs were associated with risk of AMR, and the subset of C1q-reactive DSAs were less informative ( 21 ). Pathologic classification of AMR in 37 EMB correlated with circulating DSA and endothelial activation ( 22 ).…”

Application, technical issues, and interpretation of C1q for graft outcome

“…Of those, 73.1% were C1q+, leading them to suggest that by using C1q, CDC XM could be safely eliminated and replaced by VXM resulting in less shipment of donor material, shorter CIT, less DGF, and fewer false-positive XMs while not disqualifying highly sensitized patients. A single study of pretransplant allosensitization and outcomes in sensitized and unsensitized heart recipients [ 19 ] found no association of C1q with AMR, but the authors noted that a prospective negative CDC XM was required that likely eliminated any preformed C1q+ DSA patients.…”