Donor‐specific antibodies: Can they predict C4d deposition in pediatric heart recipients?

Abstract

There is limited evidence regarding the utility of circulating DSA in surveillance for AMR of pediatric heart recipients. Our hypothesis is that quantitation of DSA improves their power for predicting a C4d+, an integral component in the current diagnostic criteria of AMR. All pediatric recipients transplanted between 10/2005 and 1/2011 were retrospectively reviewed for DSA determined within 48 h of EMB. C4d+ was defined as >25% endothelial cell staining by immunohistochemical methods. A total of 183 paired DSA-EMB determinations were identified in 60 patients, a median of three paired studies per patient (range: 1-9). DSA were detected in 60 of these determinations. A receiver-operating characteristic plot identified a threshold single-antibody MFI of >6000 that strongly correlated with C4d+ (p < 0.0001) with a high negative predictive value (0.97) and specificity (0.95). The sensitivity and positive predictive values were 0.71 and 0.60, respectively. The predictive power of single-antigen DSA for C4d deposition was improved in pediatric heart recipients using an institution-specific MFI threshold value. In post-transplant care, quantitative DSA should be an essential component in the surveillance for AMR.

HLA molecular epitope mismatching and long-term graft loss in pediatric heart transplant recipients

“…Specifically, not all graft injury is antibody-mediated, not all DSAs result in antibodymediated rejection or graft injury, and it remains difficult to predict which DSAs will be pathologic in a given patient. 16,20,21 HLA mismatching at the allelic and structural levels may predispose recipients to graft injury via pathways that do not involve DSAs, such as T cell-mediated responses, which are more difficult to measure.…”

The use of circulating donor specific antibody to predict biopsy diagnosis of antibody-mediated rejection and to provide prognostic value after heart transplantation in children

“…First, the prevalence of at least 1 positive DSA in 41% of patients in this series is notable compared with other series of pediatric recipients of HT. Peng et al 9 reported 50% of children with at least 1 positive DSA test. A recent communication from Toronto reported de novo DSA in the first year after pediatric HT in 48% of their cohort.…”

“…Additionally, the sensitivity and specificity of class I and class II MFI levels to predict the presence of any pAMR (grades 1h, 1i, 2, or 3) was evaluated using the above-mentioned pAMR grades and increasing the definition of a positive MFI cutoff by intervals of 100. 9,14 Receiver operating characteristic (ROC) analysis was used to determine the MFI cutoff with optimal sensitivity and specificity for class I and class II antibodies. ROC analysis is used to determine the relationship between specificity and sensitivity with each point on the figure representing the specificity and sensitivity for a given MFI cutoff.…”

“…The presence of donor specific antibody (DSA) has been identified as a risk factor for the development of AMR after HT, [9][10][11] and it is recommended that testing for DSA be performed when there is biopsy diagnosis of AMR. 3 At the present time, the diagnosis of pAMR requires invasive EMB, which can be associated with procedural complications.…”

Donor-specific HLA Antibodies Are Associated With Late Allograft Dysfunction After Pediatric Liver Transplantation

“…Similarly, O’Leary et al found that higher MFI DSA were associated with chronic rejection in adult LTx recipients (5). The importance of antibody strength has also been demonstrated in recipients of pediatric heart transplantation, where DSA with low MFI have been reported to occur frequently (in 50% of patients), but alone are insufficient to predict C4d deposition and antibody mediated rejection (27). In our cohort, the SAB-C1q assay only detected DSA that were strongly positive (MFI > 13000).…”