Abstract
Aim: We hypothesized that the non-complement binding of de novo donor specific antibodies (DSA) detected after heart transplant (HT) confer a lower risk for acute rejections and coronary artery vasculopathy (CAV). The purpose of this study was to compare the clinical outcomes between pediatric HT recipients with C1q+ and C1q- fixing de novo DSA Methods: 127 patients from January 2005 to December 2014 were analyzed in this study to evaluate the outcomes including acute rejections and CAV of pediatric HT recipients who had C1q+ DSA compared to those with C1q- DSA. Serum samples from patients with circulating DSA were analyzed for C1q fixing according to the manufacturer’s protocol (C1qScreen, One Lambda). Results: Out of 127 patients transplanted between 2005 and 2014, 59 (46.4%) patients developed de novo DSA, of those 37 (62.7%) had C1q+ DSA. No difference in baseline characteristics: age at HT, gender, pre-HT diagnosis of CHD, ischemic time, number of HLA mismatch and pre-HT PRA >10. We found that DSA strength is significantly associated with C1q+ (C-statistics 0.89 and p <0.05) and at cut off 7000 MFI has 80% sensitivity and 80% specificity. C1q positive rate varied according to DSA class type: Class I (25% C1q+), class II (66% C1q +) and Class I and II (67% C1q+). C1q+ DSA patients had 2.4 times higher rate of acute rejection episodes compared to those with C1q- DSA. C1q+ DSA patients had significantly higher rates of CAV at 10-yr post-HT compared to C1q- DSA patients (72% vs 28%) (Figure) (P<0.001). C1q+ DSA patients had a trend towards poor allograft survival at 10-yr post-HT compared to C1q-DSA patients (70% vs 52%) (p =0.15). Conclusions: De novo DSA which are C1q+ have significantly greater deleterious effect on long-term allograft outcome in pediatric heart transplant recipients. Thus, measuring DSA and determining their complement binding capacity is helpful in assessing the risk of cardiac allograft vasculopathy. Figure:
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