# Unveiling systemic responses in kidney transplantation: interplay between the allograft transcriptome and serum proteins

## TL;DR

This study explores how gene activity in transplanted kidneys is linked to proteins in blood serum, revealing systemic immune responses.

## Contribution

The study establishes a biological link between kidney allograft gene expression and serum proteins, offering a framework for biomarker development.

## Key findings

- RNA transcripts in kidney grafts form distinct gene networks with specific functional profiles.
- Two opposing axes related to metabolism and inflammation were identified in the allograft and serum.
- The identified axes correlate with allograft function but not with interstitial fibrosis or proteinuria.

## Abstract

Immunity, as defined by systems biology, encompasses a holistic response throughout the body, characterized by intricate connections with various tissues and compartments. However, this concept has been rarely explored in kidney transplantation. In this proof-of-concept study, we investigated a direct association between the allograft phenotype and serum protein signatures. Time-matched samples of graft biopsies and blood serum were collected in a heterogeneous cohort of kidney-transplanted patients (n = 15) for bulk RNA sequencing and proteomics, respectively. RNA transcripts exhibit distinct and reproducible, coregulated gene networks with specific functional profiles. We measured 159 serum proteins and investigated correlations with gene expression networks. Two opposing axes—one related to metabolism and the other to inflammation—were identified. They may represent a biological continuum between the allograft and the serum and correlate with allograft function, but not with interstitial fibrosis or proteinuria. For signature validation, we used two independent proteomic data sets (n = 21). Our findings establish a biological link between the allograft transcriptome and the blood serum proteome, highlighting systemic immune effects in kidney transplantation and offering a promising framework for developing allograft-linked biomarkers.