Genes associated with antibody-dependent cell activation are overexpressed in renal biopsies from patients with antibody-mediated rejection

被引:18
|
作者
Suviolahti, Elina [1 ]
Ge, Shili [1 ]
Nast, Cynthia C. [3 ]
Mirocha, James [4 ,5 ]
Karasyov, Artur [1 ]
White, Molly [1 ]
Jordan, Stanley C. [6 ]
Toyoda, Mieko [2 ]
机构
[1] Cedars Sinai Med Ctr, Comprehens Transplant Ctr, Transplant Immunol Lab, Los Angeles, CA 90048 USA
[2] Univ Calif Los Angeles, Cedars Sinai Med Ctr, Sch Med, Comprehens Transplant Ctr,Transplant Immunol Lab, Los Angeles, CA 90048 USA
[3] Univ Calif Los Angeles, Cedars Sinai Med Ctr, Sch Med, Dept Pathol, Los Angeles, CA 90048 USA
[4] Cedars Sinai Med Ctr, Res Inst, Biostat Core, Los Angeles, CA 90048 USA
[5] Cedars Sinai Med Ctr, Gen Clin Res Ctr & Cardiothorac Surg, Los Angeles, CA 90048 USA
[6] Univ Calif Los Angeles, Cedars Sinai Med Ctr, Sch Med, Comprehens Transplant Ctr, Los Angeles, CA 90048 USA
关键词
Antibody-mediated allograft rejection; Anti-HLA antibody; Natural killer cell; Antibody-dependent cellular cytotoxicity; Gene expression; Kidney biopsy; DONOR KIDNEY-TRANSPLANTATION; NK CELLS; COMPLEMENT; DESENSITIZATION; TRANSCRIPTS; INVOLVEMENT; EXPRESSION; DIAGNOSIS; INJURY;
D O I
10.1016/j.trim.2014.11.215
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Introduction: Antibody-mediated rejection (ABMR) is dependent on complement activating donor-specific anti-HLA antibodies (DSA). This is commonly detected by C4d deposition in allografts. However, recent data define a C4d negative ABMR phenotype suggesting a role for complement-independent DSA injury, antibody-dependent cellular cytotoxicity (ADCC). Methods: Here, we established an in vitro ADCC model that identified human ADCC-activated genes using microarray analysis. We subsequently interrogated renal allograft biopsies from patients with ABMR and controls for mRNA expression of the ADCC-activated gene set. Results: We identified 13 ADCC-activated genes. Six gene expression assays including 8 of the 13 genes (CCL3, CCL4/CCL4L1/CCL4L2, CD160, IFNG, NR4A3 and XCL1/XCL2) were analyzed in 127 kidney biopsies obtained from HLA-sensitized (HS), non-HS patients and control individuals. Most ADCC-activated genes showed significantly higher expression in the transplant samples compared to the controls (p < 0.0005). The gene expression levels were significantly higher in HS and non-HS transplant patients who developed ABMR compared to those who did not (p = 0.04-0.002). There was no difference in the gene expression levels between C4d positive and negative ABMR (p = 0.26-0.99). Samples from high PRA (>80%) or positive DSA patients showed higher gene expression levels for the ADCC-activated genes compared to low PRA (<80%) and negative DSA patients (p = 0.04-0.001). Conclusion: ADCC pathways are active in transplant patients with ABMR, and likely mediate allograft injury, providing a potential mechanism for C4d negative ABMR. (C) 2014 Elsevier B.V. All rights reserved.
引用
收藏
页码:9 / 17
页数:9
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