Renal Transplant Patients Biopsied for Cause and Tested for C4d, DSA, and IgG Subclasses and C1q: Which Humoral Markers Improve Diagnosis and Outcomes?

Renal Transplant Patients Biopsied for Cause and Tested for C4d, DSA, and IgG Subclasses and C1q: Which Humoral Markers Improve Diagnosis and Outcomes?
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DOI:
10.1155/2017/1652931
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发表时间:
2017-01-01
影响因子:
4.1
通讯作者:
Shah, Tariq
Shah, Tariq
中科院分区:
医学3区
文献类型:
--
作者:
Cicciarelli, James C.;Lemp, Nathan A.;Shah, Tariq

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供者特异性抗体(DSA)与肾移植排斥反应之间的关系已被普遍确立,但也有DSA存在而无排斥反应的病例。我们检查了73例肾移植受者活检移植功能障碍与DSA检测结果可用:23例患者弥漫性阳性C4d(C4d+),25例C4d局灶性阳性,25例C4d阴性(C4d-)。我们在DSA+和C4d+患者组中进行了C1 q和IgG亚类检测。确定C4d+组的移植物结局。所有23例C4d+患者均进行了IgG DSA,平均12,500 MFI(累积DSA MFI)。C4d患者DSA平均值小于500 MFI。在C4d+活检的患者中,100%有IgG DSA,70%有C1 q + DSA,83%有补体结合IgG亚类抗体。有趣的是,在23名接受者的血清中的10名中观察到IgG 4,但总是沿着补体固定IgG 1,并且我们先前在单独存在IgG 4 DSA的患者中观察到极好的功能。累积DSA超过10,000 MFI与C4 d沉积和补体结合相关。移植物丢失和C1 q阳性之间无显著相关性,IgG亚类分析似乎与C4d+患者组中的补体结合抗体更相关。
The association between donor specific antibodies (DSA) and renal transplant rejection has been generally established, but there are cases when a DSA is present without rejection. We examined 73 renal transplant recipients biopsied for transplant dysfunction with DSA test results available: 23 patients diffusely positive for C4d (C4d+), 25 patients focally positive for C4d, and 25 patients negative for C4d (C4d-). We performed C1q and IgG subclass testing in our DSA+ and C4d+ patient group. Graft outcomes were determined for the C4d+ group. All 23 C4d+ patients had IgG DSA with an average of 12,500 MFI (cumulative DSA MFI). The C4d patients had average DSA less than 500 MFI. Among the patients with C4d+ biopsies, 100% had IgG DSA, 70% had C1q+ DSA, and 83% had complement fixing IgG subclass antibodies. Interestingly, IgG4 was seen in 10 of the 23 recipients' sera, but always along with complement fixing IgG1, and we have previously seen excellent function in patients when IgG4 DSA exists alone. Cumulative DSA above 10,000 MFI were associated with C4d deposition and complement fixation. There was no significant correlation between graft loss and C1q positivity, and IgG subclass analysis seemed to be a better correlate for complement fixing antibodies in the C4d+ patient group.