Phosphorylated S6 ribosomal protein: A novel biomarker of antibody-mediated rejection in heart allografts

被引:86
作者
Lepin, E. J.
Zhang, Q.
Zhang, X.
Jindra, P. T.
Hong, L. S.
Ayele, P.
Peralta, M. V. P.
Gjertson, D. W.
Kobashigawa, J. A.
Wallace, W. D.
Fishbein, M. C.
Reed, E. F. [1 ]
机构
[1] Univ Calif Los Angeles, Immunogenet Ctr, David Geffen Sch Med, Los Angeles, CA 90024 USA
[2] Univ Calif Los Angeles, Dept Pathol & Lab Med, David Geffen Sch Med, Los Angeles, CA USA
[3] Univ Calif Los Angeles, Div Clin Fac Med, David Geffen Sch Med, Heart Transplant Program, Los Angeles, CA USA
关键词
alloantibodies; endothelial cells; heart/lung transplantation; histocompatibility antigens; rejection;
D O I
10.1111/j.1600-6143.2006.01355.x
中图分类号
R61 [外科手术学];
学科分类号
摘要
We tested the hypothesis that phosphorylation of S6 ribosomal protein (S6RP), a downstream target of the PI3K/Akt/mTOR pathway, is a biomarker of antibody-mediated rejection (AMR) in heart allografts. Primary cultures of human aortic and microvascular endothelial cells (EC) were treated with anti-HLA class I and class II antibodies (Ab) and cell lysates were studied for phosphorylation of S6 ribosmal protein at Serine(235/236) (p-S6RP). Treatment of cultured EC with anti-class I and class II Ab stimulated S6RP phosphorylation. Immunohistochemical techniques were used to detect the level of p-S6RP in endomyocardial biopsies (n = 131) from 46 heart transplant recipients and the results were correlated with histopathological diagnosis of rejection, C4d staining, production of posttransplant anti-HLA Ab and clinical outcome. Increased phosphorylation of S6RP in endomyocardial biopsies was significantly associated with the diagnosis of AMR (p < 0.0001). No significant association between acute cellular rejection (ACR) and p-S6RP was observed. C4d staining was positively associated with both AMR and p-S6RP. Posttransplant anti-HLA class II Ab production was also significantly associated with a positive p-S6RP status in cardiac biopsies. These results indicate that p-S6RP is a useful biomarker for the diagnosis of AMR.
引用
收藏
页码:1560 / 1571
页数:12
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