Department of Chronic Diseases, Metabolism & Ageing (CHROMETA), Laboratory of Respiratory Diseases & Thoracic Surgery (BREATHE), UZ/KU Leuven, Leuven, Belgium.
Department of Pneumology, University Hospital Vall d'Hebron, Barcelona, Spain.
Transpl Immunol. 2021 Feb;64:101352. doi: 10.1016/j.trim.2020.101352. Epub 2020 Nov 17.
In recent years, the utility of vascular complement factor 4d (C4d) deposition as diagnostic tool for antibody mediated rejection (AMR) after lung transplantation, has become a controversial issue. We aimed to pinpoint the problematic nature of C4d as biomarker with a simple experiment. We quantified C4d in broncho-alveolar lavage (BAL) of lung transplant patients with diverse post-transplant complications in 3 different settings of clinically clear cases of: 1/ chronic lung allograft dysfunction (CLAD); 2/ acute complications acute rejection (AR), lymphocytic bronchiolitis (LB), antibody-mediated rejection (AMR) and respiratory infection (INF); 3/ patients with parallel C4d immunostaining and Anti-HLA. All groups were compared to BAL of stable patients. C4d was measured via standard ELISA. C4d was increased in CLAD, predominantly in RAS (p = 0.0026) but not in BOS (p = 0.89). C4d was increased in all acute events, AR (p = 0.0025), LB (p < 0.0001), AMR (p = 0.0034), infections (p < 0.0001). In patients with parallel C4d immunostaining and serum HLA antibodies, C4d was increased in C4d-/HLA- (p = 0.0011); C4d-/HLA+ (p = 0.013); HLA+/C4d + (p = 0.0081). A correlation of systemic C-reactive protein (CRP) with C4d was found in all patients (r = 0.49; p < 0.0001). We hypothesize that free C4d in BAL may only be representative of a general immune response in the transplanted lung.
近年来，血管补体因子 4d（C4d）沉积作为肺移植后抗体介导排斥反应（AMR）的诊断工具，已成为一个有争议的问题。我们旨在通过一个简单的实验确定 C4d 作为生物标志物的问题性质。我们在 3 种不同的临床明确情况下，对有不同移植后并发症的肺移植患者的支气管肺泡灌洗液（BAL）中定量检测 C4d：1/慢性肺移植物功能障碍（CLAD）；2/急性并发症急性排斥反应（AR）、淋巴细胞性细支气管炎（LB）、抗体介导的排斥反应（AMR）和呼吸道感染（INF）；3/并行 C4d 免疫染色和抗 HLA 的患者。所有组均与稳定患者的 BAL 进行比较。通过标准 ELISA 测量 C4d。CLAD 患者的 C4d 增加，主要在 RAS（p=0.0026）中，但在 BOS 中没有增加（p=0.89）。所有急性事件中 C4d 增加，AR（p=0.0025）、LB（p<0.0001）、AMR（p=0.0034）、感染（p<0.0001）。在并行 C4d 免疫染色和血清 HLA 抗体的患者中，C4d 在 C4d-/HLA-（p=0.0011）；C4d-/HLA+（p=0.013）；HLA+/C4d+（p=0.0081）中增加。在所有患者中均发现系统 C 反应蛋白（CRP）与 C4d 之间存在相关性（r=0.49；p<0.0001）。我们假设 BAL 中的游离 C4d 可能仅代表移植肺中的一般免疫反应。
