Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, the Netherlands.
Department of Nephrology and Transplantation Medicine, Kantonsspital St. Gallen, St. Gallen, Switzerland.
Transplantation. 2020 May;104(5):1026-1032. doi: 10.1097/TP.0000000000002909.
HLA-specific memory B cells may contribute to the serum HLA antibody pool upon antigen reexposure. The aim of this pilot study was to investigate the presence of concurrent donor-specific memory B cell-derived HLA antibodies (DSA-M) in renal allograft recipients with pretransplant donor-specific HLA antibodies (DSA) and its association with occurrence of antibody-mediated rejection (AMR) using a recently developed method.
Twenty patients with Luminex single antigen bead (SAB) assay-defined DSA but negative complement-dependent cytotoxicity crossmatches were enrolled. Plasma samples and peripheral blood mononuclear cells were collected at 3 timepoints (pretransplant, mo 6, mo 12). We analyzed IgG-purified and concentrated culture supernatants from polyclonally activated peripheral blood mononuclear cells using SAB assays and compared HLA antibody profiles with same day plasma results.
Plasma SAB analysis revealed 35 DSA in 20 patients pretransplant. DSA-M were detected in 9 of 20 (45%) patients and for 10 of 35 specificities (29%). While median mean fluorescence intensity values of DSA with concurrent DSA-M (5877) were higher than those of DSA without DSA-M (1476), 3 of 6 patients with AMR and low mean fluorescence intensity DSA (<3000) had DSA-M. Overall, pretransplant DSA/DSA-Mpos allograft recipients showed a higher incidence of biopsy-proven (sub)clinical AMR (P = 0.032) and a higher extent (g≥1 + ptc≥1) of microvascular inflammation (67% vs 9%, P = 0.02). In 17 patients (28 DSA) with posttransplant analyses, persisting DSA posttransplant had more often DSA-M (6/12; 50%) than nonpersisting DSA (2/16; 13%).
Assessment of DSA-M might be a novel tool to supplement serum HLA antibody analysis for pretransplant risk stratification in patients with DSA.
HLA 特异性记忆 B 细胞在抗原再次暴露时可能会导致血清 HLA 抗体池增加。本研究旨在采用新开发的方法，检测具有移植前 HLA 特异性抗体（DSA）的肾移植受者中是否存在同时存在的供体特异性记忆 B 细胞衍生的 HLA 抗体（DSA-M），并探讨其与抗体介导的排斥反应（AMR）的关系。
我们纳入了 20 例 Luminex 单抗原珠（SAB）检测定义的 DSA 但补体依赖性细胞毒性交叉配型阴性的患者。在 3 个时间点（移植前、mo6、mo12）采集了血浆样本和外周血单个核细胞。我们使用 SAB 检测分析了多克隆激活的外周血单个核细胞中 IgG 纯化和浓缩培养上清液，并将 HLA 抗体谱与同日的血浆结果进行了比较。
移植前 20 例患者的血浆 SAB 分析显示 35 例 DSA。在 20 例患者中的 9 例（45%）和 35 个特异性中的 10 个（29%）检测到了 DSA-M。虽然具有 DSA-M 的 DSA 的中位平均荧光强度值（5877）高于没有 DSA-M 的 DSA（1476），但在 6 例 AMR 患者和低平均荧光强度 DSA（<3000）中，有 3 例具有 DSA-M。总体而言，移植前 DSA/DSA-Mpos 移植受者的活检证实的（亚）临床 AMR 发生率更高（P = 0.032），微血管炎症的程度（g≥1 + ptc≥1）也更高（67% vs 9%，P = 0.02）。在 17 例（28 例 DSA）有移植后分析的患者中，移植后持续存在的 DSA 更常伴有 DSA-M（6/12；50%），而非持续存在的 DSA 则不然（2/16；13%）。
评估 DSA-M 可能是一种新的工具，可以补充移植前血清 HLA 抗体分析，用于具有 DSA 的患者的移植前风险分层。
