关键词: Granzyme B Perforin defense against pathogens induction therapies kidney transplant recipients thymoglobulin

来  源:   DOI:10.3390/biomedicines12061258   PDF(Pubmed)

Abstract:
Peripheral blood mononuclear cells contain secretory granules with Perforin and Granzyme B for defense against pathogens. The objective of the present study was to compare the effects of immunosuppressive induction therapies on Perforin and Granzyme B transcripts in kidney transplant recipients. Transcripts were determined in 408 incident kidney transplant recipients eight days posttransplant using quantitative real-time PCR. Compared to 90 healthy subjects, the median Perforin transcripts were lower in kidney transplant recipients with blood-group ABO-incompatible donors (N = 52), compatible living donors (N = 130), and deceased donors (N = 226) (25.7%; IQR, 6.5% to 46.0%; 31.5%; IQR, 10.9% to 57.7%; and 35.6%; IQR, 20.6% to 60.2%; respectively; p = 0.015 by the Kruskal-Wallis test). Kidney transplant recipients who were treated with thymoglobulin (N = 64) had significantly lower Perforin as well as Granzyme B compared to all other induction therapies (N = 344) (each p < 0.001). Receiver operator characteristics analysis showed that both Perforin (area under curve, 0.919) and Granzyme B (area under curve, 0.915) indicated thyroglobulin-containing induction therapies. Regression analysis showed that both reduction in plasma creatinine and human leukocyte antigen mismatches were positively associated with elevated Perforin/Granzyme B transcript ratio posttransplant. We conclude clinical parameters and therapies affect Perforin and Granzyme B transcripts posttransplant.
摘要:
外周血单核细胞含有分泌颗粒,带有穿孔素和颗粒酶B,用于防御病原体。本研究的目的是比较免疫抑制诱导疗法对肾移植受者穿孔素和颗粒酶B转录本的影响。移植后8天,使用定量实时PCR确定了408例肾移植受者的转录本。与90名健康受试者相比,在有血型ABO不相容供者的肾移植受者中,穿孔素转录本的中位数较低(N=52),相容的活体供体(N=130),和已故捐赠者(N=226)(25.7%;IQR,6.5%至46.0%;31.5%;IQR,10.9%至57.7%;和35.6%;IQR,20.6%至60.2%;通过Kruskal-Wallis检验,p=0.015)。与所有其他诱导疗法(N=344)相比,接受胸腺球蛋白(N=64)治疗的肾移植受者的穿孔素和颗粒酶B显着降低(每个p<0.001)。接收机算子特征分析表明,两者都是Perforin(曲线下面积,0.919)和颗粒酶B(曲线下面积,0.915)表明含有甲状腺球蛋白的诱导疗法。回归分析表明,血浆肌酐和人类白细胞抗原错配的减少与移植后穿孔素/粒酶B转录比的升高呈正相关。我们得出的结论是,临床参数和疗法会影响移植后的穿孔素和颗粒酶B转录本。
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