原发性肾移植受者 IgM 和 IgG3 抗 HLA 同种异体抗体的影响。

Impact of IgM and IgG3 anti-HLA alloantibodies in primary renal allograft recipients.

机构信息

1 Terasaki Foundation Laboratory, Los Angeles, CA. 2 Department of Pathology, Brody School of Medicine at East Carolina University, Greenville, NC. 3 Department of Surgery, Brody School of Medicine at East Carolina University, Greenville, NC. 4 Department of Medicine, Brody School of Medicine at East Carolina University, Greenville, NC. 5 Eastern Nephrology Associates, Greenville, NC. 6 Vidant Medical Center, Greenville, NC. 7 Address correspondence to: Matthew J. Everly, M.D., Terasaki Foundation, 11570 W. Olympic Blvd., Los Angeles, CA 90064.

出版信息

Transplantation. 2014 Mar 15;97(5):494-501. doi: 10.1097/01.TP.0000441362.11232.48.

DOI:10.1097/01.TP.0000441362.11232.48

PMID:24487396

Abstract

BACKGROUND

With standard IgG donor-specific anti-HLA antibody (DSA) testing, it is unclear which immunoglobulin-G (IgG) DSA positive patients will fail. We looked further into the immune response by studying immunoglobulin-M (IgM) and IgG subclass 3 (IgG3) DSA to determine if these identify the IgG DSA patients at highest risk for allograft loss.

METHODS

In 189 consecutively transplanted primary renal allograft recipients, sera were collected sequentially pre- and posttransplant. Of the 189, 179 patients had sera available to retrospectively test for anti-HLA IgG, IgM, and IgG3 antibodies via LABScreen single-antigen bead assay and were included in the study. All patients had a negative crossmatch. Per patient, all DSA (IgM, IgG3, and IgG) refers to the same serologic specificity.

RESULTS

Overall, 100 (56%) patients developed an alloimmune response (IgM or IgG DSA positive, or both). Ninety-five patients developed IgM DSA and 47 patients developed IgG DSA. IgM DSA was detected in 42 of 47 patients with IgG DSA. IgM DSA alone did not increase the allograft loss risk, whereas IgG DSA did (P=0.002). Once IgG DSA appeared, IgM DSA persisted in 33 patients and an isotype switch to IgG3 positive DSA occurred in 25 patients. Patients with IgM persistent IgG3 positive DSA (n=19) were more likely to have allograft failure than those without (P=0.02).

CONCLUSION

This study shows the evolution of the humoral immune response from IgM to IgG DSA posttransplant. We found that development of IgM persistent IgG3 positive DSA identifies the most dangerous IgG DSA subpopulation.

摘要

背景

在使用标准 IgG 供体特异性抗 HLA 抗体（DSA）检测时，尚不清楚哪些 IgG DSA 阳性患者会失败。我们通过研究免疫球蛋白-M（IgM）和 IgG 亚类 3（IgG3）DSA 进一步研究了免疫反应，以确定这些是否能识别出发生同种异体移植物丢失风险最高的 IgG DSA 患者。

方法

在 189 例连续移植的原发性肾移植受者中，在移植前后分别采集了血清。在这 189 例患者中，有 179 例患者的血清可用于通过 LABScreen 单抗原珠检测法进行回顾性检测抗 HLA IgG、IgM 和 IgG3 抗体，且这些患者被纳入本研究。所有患者的交叉配型均为阴性。每位患者的所有 DSA（IgM、IgG3 和 IgG）均指相同的血清学特异性。

结果

总体而言，100 例（56%）患者发生了同种免疫反应（IgM 或 IgG DSA 阳性，或两者均阳性）。95 例患者发生了 IgM DSA，47 例患者发生了 IgG DSA。在 47 例 IgG DSA 患者中，有 42 例检测到 IgM DSA。IgM DSA 单独出现并不会增加移植物丢失风险，而 IgG DSA 则会（P=0.002）。一旦出现 IgG DSA，IgM DSA 会在 33 例患者中持续存在，且 25 例患者会发生 IgG3 阳性 DSA 的同种型转换。与无 IgM 持续 IgG3 阳性 DSA 的患者（n=19）相比，IgM 持续 IgG3 阳性 DSA 的患者更有可能发生移植物衰竭（P=0.02）。