Induction Therapies Determine the Distribution of Perforin and Granzyme B Transcripts in Kidney Transplant Recipients

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.

Keywords

• Perforin
• Granzyme B
• kidney transplant recipients
• induction therapies
• thymoglobulin
• defense against pathogens