Taniguchi Michiko, Rebellato Lorita M, Briley Kimberly P, Haisch Carl E, Bolin Paul, Banuelos Nubia, Hopfield Judy, Terasaki Paul I, Everly Matthew J
City of Hope, Duarte, CA.
The Brody School of Medicine at East Carolina University, Greenville, NC.
Clin Transpl. 2015;31:293-301.
Human leukocyte antigen (HLA) antibodies are a major cause of graft loss in mismatched transplant recipients. However, the time to graft loss resulting from antibody induced injury is unpredictable. The unpredictable nature of antibodies may be related to the subclass of antibodies. In this study, HLA immunoglobulin G (IgG) subclasses were investigated to determine whether a unique IgG subclass composition could better identify those patients at eminent risk for graft loss.
The serial serum samples from the 57 patients with post-transplant HLA class II donor specific antibodies (DSA) were tested for the three IgG subclasses (IgG1, IgG3, and IgG4).
IgG3 and IgG4 were highly prevalent in failed patients compared to functioning patients (82 % vs. 34%, 45% vs. 20%, respectively). IgG3 development showed a distinct subclass trend between failed and functioning patients with poor graft survival (log rank p=0.0006). IgG1 was almost equally abundant in both groups (100% and 97%, respectively). Of the 5 patterns of IgG subclass combinations observed, IgG1+3+ showed the strongest association with graft failure (hazard ratio 3.14, p=0.007).
Patients with IgG3 subclass HLA DSA showed lower graft survival. Post-transplant monitoring for IgG subclasses rather than total IgG monitoring may identify patients at risk for graft failure.
人类白细胞抗原（HLA）抗体是移植配型不匹配受者移植物丢失的主要原因。然而，抗体诱导损伤导致移植物丢失的时间是不可预测的。抗体这种不可预测的特性可能与抗体的亚类有关。在本研究中，对HLA免疫球蛋白G（IgG）亚类进行了研究，以确定独特的IgG亚类组成是否能更好地识别那些有移植物丢失高风险的患者。
对57例移植后出现HLA II类供者特异性抗体（DSA）患者的系列血清样本检测三种IgG亚类（IgG1、IgG3和IgG4）。
与移植功能良好的患者相比，IgG3和IgG4在移植失败患者中高度流行（分别为82%对34%，45%对20%）。在移植失败和移植功能良好但移植物存活不佳的患者之间，IgG3的产生呈现出明显的亚类趋势（对数秩检验p = 0.0006）。两组中IgG1的含量几乎相同（分别为100%和97%）。在观察到的5种IgG亚类组合模式中，IgG1+3+与移植失败的关联最强（风险比3.14，p = 0.007）。
具有IgG3亚类HLA DSA的患者移植物存活率较低。移植后监测IgG亚类而非总IgG，可能有助于识别有移植失败风险的患者。
