Exploring kidney allograft rejection: A proof-of-concept study using spatial transcriptomics
In this proof-of-concept study, spatial transcriptomics combined with public single-cell RNA sequencing data were used to explore the potential of this technology to study kidney allograft rejection. We aimed to map gene expression patterns within diverse pathological states by examining biopsies classified across non-rejection, T cell-mediated acute rejection, and interstitial fibrosis and tubular atrophy (IFTA). Our results revealed distinct immune cell signatures, including those of T and B lymphocytes, monocytes, mast cells, and plasma cells, and their spatial organization within the renal interstitium. We also mapped chemokine receptors and ligands to study immune-cell migration and recruitment. Finally, our analysis demonstrated differential spatial enrichment of transcription signatures associated with kidney allograft rejection across various biopsy regions. Interstitium regions displayed higher enrichment scores for rejection-associated gene expression patterns than did tubular areas, which had negative scores. This implies that these signatures are primarily driven by processes unfolding in the renal interstitium. Overall, this study highlights the value of spatial transcriptomics for revealing cellular heterogeneity and immune signatures in renal transplant biopsies, and demonstrates its potential for studying the molecular and cellular mechanisms associated with rejection. However, certain limitations must be borne in mind regarding the development and future applications of this technology. Overall design: Using spatial transcriptomics, this study examined three kidney post-implantation biopsies with different histological phenotypes. The Banff criteria were used to evaluate the samples. Each sample exhibited different rejection levels with varying parameter scores, including i, t, v, and g. The diagnostic categories for biopsy samples included acute cellular rejection, interstitial fibrosis and tubular atrophy (IFTA), and unaltered (non-rejection).