Fichtner Alexander, Süsal Caner, Höcker Britta, Rieger Susi, Waldherr Rüdiger, Westhoff Jens H, Sander Anja, Opelz Gerhard, Tönshoff Burkhard
Department of Pediatrics I, University Children's Hospital Heidelberg, Im Neuenheimer Feld 430, D-69120, Heidelberg, Germany.
Department of Transplantation Immunology, Institute of Immunology, University of Heidelberg, Heidelberg, Germany.
Pediatr Nephrol. 2016 Jul;31(7):1157-66. doi: 10.1007/s00467-016-3322-8. Epub 2016 Feb 29.
We investigated the prognostic value of overall and complement-binding donor-specific HLA antibodies (DSA) in pediatric patients undergoing clinically indicated graft biopsies and their association with graft outcome and specific histological lesions.
Sera of 62 patients at time of indication biopsy ≥1 year posttransplant were assessed for DSA and C1q-fixing DSA by single-antigen bead (SAB) technology.
Twenty-six patients (42 %) were DSA-positive at time of indication biopsy and nine (15 %) were C1q-positive. At 4 years postbiopsy, patients with C1q-positivity had a low graft survival (11 %) compared to DSA-positive, C1q-negative patients (82 %, p = 0.001) and to DSA-negative patients (88 %, p < 0.001). The majority (89 %) of C1q-positive patients were diagnosed with active chronic antibody-mediated rejection (ABMR). C1q DSA-positivity [adjusted hazard ratio (HR) 6.35], presence of transplant glomerulopathy (HR 9.54), and estimated glomerular filtration rate (eGFR) at the time of indication biopsy (HR 0.91) were risk factors for subsequent graft loss.
The presence of C1q-positive DSA in the context of an indication biopsy identifies a subgroup of pediatric renal transplant recipients with a markedly increased risk of subsequent graft loss. Because a fraction of DSA-positive patients escape rejection or graft dysfunction, the C1q assay increases the specificity of a positive DSA result regarding unfavorable transplant outcome.
我们研究了接受临床指征性移植肾活检的儿科患者中总体及补体结合供者特异性 HLA 抗体（DSA）的预后价值，以及它们与移植肾结局和特定组织学病变的关联。
采用单抗原微珠（SAB）技术评估 62 例移植后≥1 年进行指征性活检时患者的血清 DSA 和 C1q 结合 DSA。
26 例患者（42%）在指征性活检时 DSA 呈阳性，9 例（15%）C1q 呈阳性。活检后 4 年，C1q 阳性患者的移植肾存活率较低（11%），而 DSA 阳性、C1q 阴性患者的移植肾存活率为 82%（p = 0.001），DSA 阴性患者的移植肾存活率为 88%（p < 0.001）。大多数（89%）C1q 阳性患者被诊断为活动性慢性抗体介导的排斥反应（ABMR）。C1q DSA 阳性[校正风险比（HR）6.35]、移植肾小球病的存在（HR 9.54）以及指征性活检时的估计肾小球滤过率（eGFR）（HR 0.91）是随后移植肾丢失的危险因素。
在指征性活检背景下存在 C1q 阳性 DSA 可识别出一组儿科肾移植受者，其随后移植肾丢失的风险显著增加。由于一部分 DSA 阳性患者可避免排斥反应或移植肾功能障碍，C1q 检测提高了 DSA 阳性结果对不良移植结局的特异性。
