Identification of a protein signature in renal allograft rejection

Abstract

Purpose: Serum creatinine functions as a poor surrogate marker of renal allograft dysfunction and long-term graft survival. By measuring multiple proteins simultaneously in the serum of transplant patients, we can identify unique protein signatures of graft dysfunction.

Experimental design: We utilized training and validation cohorts composed of healthy and volunteer subjects, stable renal transplant patients, and renal transplant patients experiencing acute allograft rejection. Utilizing our antibody microarray, we measured 108 proteins simultaneously in these groups.

Results: Using Mann-Whitney tests with Bonferroni correction, we identified ten serum proteins from 19 renal transplant patients with stable renal function, which are differentially expressed, compared to healthy control subjects. In addition, we identified 17 proteins that differentiate rejecting renal transplant recipients from stable renal transplant. Validation cohorts substantiated these findings.

Conclusion and clinical relevance: Our preliminary results support that a specific pattern of protein expression or "protein signature" may be able to differentiate between stable transplant patients from those with rejection. Future studies will focus on other etiologies of renal allograft dysfunction and the effect of treatment on protein expression and long-term outcome.

Keywords: Kidney transplantation; Protein array; Rejection.