The complement interference phenomenon as a cause for sharp fluctuations of serum anti-HLA antibody strength in kidney transplant patients
The complement interference phenomenon as a cause for sharp fluctuations of serum anti-HLA antibody strength in kidney transplant patients
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DOI：
10.1016/j.trim.2013.09.005
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发表时间：
2013-12-01
影响因子：
1.5
通讯作者：
Taupin, Jean-Luc
中科院分区：
文献类型：
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作者：
Guidicelli, Gwendaline;Anies, Guerric;Taupin, Jean-Luc
单抗原流珠（SAFB）测定极大地提高了抗HLA同种抗体抗原特异性的鉴定。然而，由于荧光抗 IgG 缀合物和血清补体之间对同种抗体的竞争引起的前带现象，它可能会低估或错过高滴度抗体。我们在移植候选者和移植受者队列中探讨了这种效应。在分别使用 I 类和/或 II 类 SAFB 检测检测至少三种不同血清的总共 292 名和 269 名患者中，我们鉴定出 9 名患者（I 类 6 名，II 类 3 名），在 18 个月的时间里，其抗体水平表现出大幅下降 (>= 75%)，随后又上升 (>= 100%)。我们假设这种突然的波动不能用自然发生的瞬时脱敏来解释。使用 EDTA 处理的血清和直接补体 C1q 染色，并使用补体依赖性细胞毒性和流式细胞术交叉配型（分别为 CDCXM 和 FCXM），通过 SAFB 测定对血清进行分析。所有情况都涉及前带现象。因为它依赖于补体激活，CDCXM 对这种现象不敏感，但 FCMXM 也不敏感，尽管它的原理与 SAFB 测定相似。四种另外的针对 IgG Fc 片段或轻链的抗人缀合物并没有规避 SAFB 的缺点。因此，抗体强度的快速下降必须使用虚拟交叉配血策略来警惕移植时受体的潜在风险。预期的移植前交叉配血仍然是最终的保障。 (C) 2013 Elsevier B.V. 保留所有权利。
The single antigen flow bead (SAFB) assay greatly improves the identification of antigenic specificity of anti-HLA alloantibodies. However, it may underestimate or miss high titer antibodies due to the prozone phenomenon caused by a competition between the fluorescent anti-IgG conjugate and serum complement, for the alloantibody. We explored this effect in our cohort of transplant candidates and transplanted recipients. Among a total of 292 and 269 patients with at least three different sera tested with class I and/or II SAFB assays respectively, we identified 9 patients (6 in class I and 3 in class II) who displayed a profound drop (>= 75%) followed by a subsequent rise (>= 100%), in strong (mean fluorescence intensity >8000) antibody levels, across an 18-month period. We postulated that such abrupt fluctuations were not explainable by naturally occurring transient desensitization. Sera were analysed with the SAFB assay using EDTA-treated serum and direct complement C1q staining, and with complement-dependent cytotoxicity and flow cytometry crossmatches (CDCXM and FCXM respectively). The prozone phenomenon was involved in all cases. Because it relies on complement activation, the CDCXM was not sensitive to this phenomenon, but the FCMXM was not either, although it resembles in its principle to the SAFB assay. Four additional anti-human conjugates targeting the IgG Fc fragment or the light chains did not circumvent the SAFB drawback. Therefore, a quick decrease in antibody strength must alert against a potential risk for recipients at the time of the transplant, using virtual crossmatch strategies. A prospective pre-transplant crossmatch still remains an ultimate safeguard. (C) 2013 Elsevier B.V. All rights reserved.