Complement-Binding Donor-Specific Anti-HLA Antibodies and Risk of Primary Graft Failure in Hematopoietic Stem Cell Transplantation.
Complement-Binding Donor-Specific Anti-HLA Antibodies and Risk of Primary Graft Failure in Hematopoietic Stem Cell Transplantation.
复制标题
DOI：
10.1016/j.bbmt.2015.05.001
复制
发表时间：
2015-08
期刊：
影响因子：
--
通讯作者：
Cao K
中科院分区：
文献类型：
--
作者：
Ciurea SO;Thall PF;Milton DR;Barnes TH;Kongtim P;Carmazzi Y;López AA;Yap DY;Popat U;Rondon G;Lichtiger B;Aung F;Afshar-Kharghan V;Ma Q;Fernández-Viña M;Champlin RE;Cao K
在所有形式的移植中，供者特异性抗人类白细胞抗原抗体(DSA)的检测与移植物排斥反应有关。DSA增加移植失败风险的机制尚不清楚。我们假设补体结合DSA与造血干细胞移植中的植入失败有关，并分析了122名预期接受DSA检测的单倍体相合移植受者。对22例同种异体致敏受者进行了C1q回顾性检测。122例患者中22例(18%)进行了DSA检查，其中19例为女性(86%)。7名DSA患者(32%)拒绝接受移植。移植失败的患者移植时的DSA中位数为10,055 MFI，而植入的患者为2,065 MFI(p=0.007)。DSA中位数为15,279MFI(范围1,554-28,615)的9例患者为C1q阳性，而DSA中位数为2,471MFI(665-12,254)的C1q阴性患者为7例(P=0.016)。在最初样本C1q检测为阳性的9名患者中，5名患者在移植时仍为C1q阳性[均为高DSA水平(中位数15,279，范围6,487-22,944)]，并经历了移植失败，而4名患者在移植前C1q阴性，所有患者均植入供体细胞(p=0.008)。总而言之，DSA水平高(5,000 MFI)和补体结合抗体(C1q阳性)的患者发生初次移植物失败的风险似乎要高得多。在进行造血干细胞移植前，应对DSA患者进行C1q评估。将DSA降低到非补体结合水平可能会防止造血干细胞移植的植入失败。
Detection of donor-specific anti-HLA antibodies (DSA) has been associated with graft rejection in all forms of transplantation. The mechanism by which DSA increase the risk of graft failure remains unclear. We hypothesized that complement-binding DSA are associated with engraftment failure in hematopoietic stem-cell transplantation and analyzed 122 haploidentical transplant recipients tested prospectively for DSA. Retrospective C1q testing was done on 22 allosensitized recipients. Twenty-two of 122 patients (18%) had DSA, 19 of which were females (86%). Seven patients with DSA (32%) rejected the graft. Median DSA level at transplant for patients who failed to engraft was 10,055 MFI versus 2,065 MFI for those who engrafted (p=0.007). Nine patients with DSA were C1q positive in the initial samples with median DSA level 15,279 MFI (range 1,554-28,615), compared with 7 C1q negative patients with median DSA level 2,471 MFI (665-12,254) (p=0.016). Of 9 patients, who tested positive for C1q in the initial samples, 5 patients remained C1q positive at time of transplant [all with high DSA levels (median 15,279, range 6,487-22,944)] and experienced engraftment failure, while 4 patients became C1q negative pre-transplant and all engrafted the donor cells (p=0.008). In conclusion, patients with high DSA levels (> 5,000 MFI) and complement-binding antibodies (C1q positive) appear to be at much higher risk of primary graft failure. C1q should be assessed in patients with DSA prior to hematopoietic stem-cell transplantation. Reduction of DSA to non-complement binding levels might prevent engraftment failure in hematopoietic stem cell transplantation.