Subclass analysis of donor HLA-specific IgG in antibody-incompatible renal transplantation reveals a significant association of IgG4 with rejection and graft failure.
Subclass analysis of donor HLA-specific IgG in antibody-incompatible renal transplantation reveals a significant association of IgG4 with rejection and graft failure.
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DOI：
10.1111/tri.12648
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发表时间：
2015-12
期刊：
影响因子：
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通讯作者：
Lowe D
中科院分区：
文献类型：
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作者：
Khovanova N;Daga S;Shaikhina T;Krishnan N;Jones J;Zehnder D;Mitchell D;Higgins R;Briggs D;Lowe D
供者HLA特异性抗体（DSA）可导致肾移植后排斥反应和移植物丢失，但通过目前的检测方法测量的其水平并不能完全预测结果。我们研究DSA的IgG亚类是否与早期排斥反应和移植失败有关。使用改良微珠测定法，在80名HLA抗体不相容的肾移植受者中，在治疗前、泛IgG水平达到峰值当天和移植后30天测定DSA水平。治疗前IgG 4水平可预测移植后前30天内的急性抗体介导的排斥反应（P = 0.003）。治疗前存在IgG 4 DSA（P = 0.008）和第30天IgG 3 DSA（P = 0.03）与移植物存活率差相关。多变量回归分析显示，除泛IgG水平外，治疗前测量的总IgG 4水平是早期排斥反应的独立风险因素，治疗前IgG 4 DSA的存在也是移植失败的独立风险因素。治疗前IgG 4 DSA水平与早期排斥发作和中期死亡删失移植物存活率的较高风险独立相关。因此，治疗前IgG4 DSA可用作生物标志物，用于预测HLA抗体不相容移植中泛IgG DSA水平较高的病例并对其进行风险分层。需要进一步的研究来证实我们的结果。
Donor HLA‐specific antibodies (DSAs) can cause rejection and graft loss after renal transplantation, but their levels measured by the current assays are not fully predictive of outcomes. We investigated whether IgG subclasses of DSA were associated with early rejection and graft failure. DSA levels were determined pretreatment, at the day of peak pan‐IgG level and at 30 days post‐transplantation in eighty HLA antibody‐incompatible kidney transplant recipients using a modified microbead assay. Pretreatment IgG4 levels were predictive of acute antibody‐mediated rejection (P = 0.003) in the first 30 days post‐transplant. Pre‐treatment presence of IgG4 DSA (P = 0.008) and day 30 IgG3 DSA (P = 0.03) was associated with poor graft survival. Multivariate regression analysis showed that in addition to pan‐IgG levels, total IgG4 levels were an independent risk factor for early rejection when measured pretreatment, and the presence of pretreatment IgG4 DSA was also an independent risk factor for graft failure. Pretreatment IgG4 DSA levels correlated independently with higher risk of early rejection episodes and medium‐term death‐censored graft survival. Thus, pretreatment IgG4 DSA may be used as a biomarker to predict and risk stratify cases with higher levels of pan‐IgG DSA in HLA antibody‐incompatible transplantation. Further investigations are needed to confirm our results.