Division of Pediatric Cardiology, UT Southwestern Medical Center, Dallas, TX.
Department of Pathology, UT Southwestern Medical Center, Dallas, TX.
Transplantation. 2018 Mar;102(3):502-509. doi: 10.1097/TP.0000000000001944.
We hypothesized C1q binding de novo donor-specific antibody (DSA) after heart transplant (HT) is a higher risk for development of coronary artery vasculopathy (CAV) in children.
A retrospective analysis of 127 pediatric HT recipients transplanted between January 2005 and December 2014 was used to determine complement (C1q)-binding de novo DSA on the outcomes of HT and the ability of the C1q assay to predict CAV development.
Of 127 patients, 59 (46.4%) developed de novo DSA, 37 of those had C1q+ DSA. There was no difference in baseline characteristics except patients who developed C1q+ DSA more often received a donor heart from a female compared with C1q- DSA group (P = 0.034). The DSA median fluorescent intensity (MFI) value of 7000 or greater had 80% sensitivity and 80% specificity (C statistics 0.89, P <0.05) for predicting positive C1q binding. Multivariate analyses identified C1q binding DSA as an independent risk for CAV with a hazard ratio (HR) of 3.25 (95% confidence interval [CI], 1.33-7.93; P = 0.0095). In multivariable Cox proportional hazard models, the covariates associated with graft loss included: C1q+ DSA (HR, 3.2; 95% CI, 1.34-7.86; P < 0.009), pre-HT renal insufficiency (HR, 11.3; 95% CI, 3.71-34.29; P < 0.0001), and pre-HT ventilator support (HR, 3.3; 95% CI, 1.39-7.81; P = 0.007).
The DSA strength in MFI correlates with positive C1q-binding activity and hence functional capabilities of DSA. Close monitoring of DSA strength in MFI and function (C1q assay) may be useful for identifying pediatric HT recipient at risk for development of CAV.
我们假设心脏移植（HT）后 C1q 结合的新出现的供体特异性抗体（DSA）是儿童发生冠状动脉血管病变（CAV）的更高风险因素。
对 2005 年 1 月至 2014 年 12 月期间接受心脏移植的 127 名儿科患者进行回顾性分析，以确定补体（C1q）结合的新出现的 DSA 对 HT 结果的影响，以及 C1q 检测在预测 CAV 发展方面的能力。
在 127 例患者中，59 例（46.4%）出现新出现的 DSA，其中 37 例为 C1q+ DSA。除了 C1q+ DSA 组患者接受女性供体心脏的比例高于 C1q-DSA 组（P = 0.034）外，两组患者的基线特征无差异。7000 或更高的 DSA 中位荧光强度（MFI）值对预测阳性 C1q 结合具有 80%的敏感性和 80%的特异性（C 统计量 0.89，P <0.05）。多变量分析表明，C1q 结合 DSA 是 CAV 的独立危险因素，危险比（HR）为 3.25（95%置信区间[CI]，1.33-7.93；P = 0.0095）。在多变量 Cox 比例风险模型中，与移植物丢失相关的协变量包括：C1q+ DSA（HR，3.2；95%CI，1.34-7.86；P <0.009）、HT 前肾功能不全（HR，11.3；95%CI，3.71-34.29；P <0.0001）和 HT 前呼吸机支持（HR，3.3；95%CI，1.39-7.81；P = 0.007）。
DSA 在 MFI 中的强度与 C1q 结合活性相关，从而与 DSA 的功能能力相关。密切监测 DSA 在 MFI 中的强度和功能（C1q 检测）可能有助于识别发生 CAV 的儿科 HT 受者。
