AI Insight
Researchers developed a method to identify genetic mismatches between kidney donors and recipients without needing donor DNA samples after transplantation. By analyzing DNA from recipients' urine cell pellets alongside the recipients' own genomic DNA, they could accurately infer donor genotypes and detect non-HLA genetic mismatches that contribute to transplant rejection. Testing on 11 kidney transplant pairs showed that urine-derived DNA significantly outperformed blood plasma DNA in identifying these mismatches across multiple genomic scales.
Why it matters
This non-invasive approach could enable ongoing monitoring of genetic compatibility after transplantation, when donor tissue samples are typically unavailable. The method may help predict long-term graft survival and personalize immunosuppression therapy by identifying specific genetic risk factors between donors and recipients.
⚠️ Preprint – Noch nicht peer-reviewed
Dieser Artikel wurde noch nicht von unabhängigen Experten begutachtet. Die Ergebnisse sind vorläufig und sollten mit Vorsicht interpretiert werden.
Non-HLA donor-recipient (D-R) genetic mismatches contribute to kidney allograft injury and long-term graft loss, but their clinical use is limited by the unavailability of donor DNA after transplantation. We tested whether non-invasively obtained, recipient-derived samples could be used to infer donor genotype and D-R mismatches. Genomic DNA (g-DNA) of 11 unselected kidney transplant recipients and donors underwent whole-exome sequencing (100x). Additional customized probes were added for intronic coverage (300x) of 55 targeted non-HLA genes of reported clinical relevance. Variants identified from sequencing results were compared with plasma cell-free DNA (cfDNA), urine cell-pellet DNA (U-DNA) obtained from the same recipients. Genome-wide-, exonic-, or non-synonymous exonic- mismatches in transmembrane or secreted proteins, and mismatches within target genes were benchmarked using donor g-DNA to generate mismatch scores for each D-R pair. Within each of these genomic scales of mismatch, U-DNA identified D-R mismatches significantly better than the corresponding cfDNA (P<0.001 for each comparison). U-DNA also identified gene-level mismatches in the LIMS1 gene, and correctly inferred established donor-origin risk alleles, including SHROOM3 and APOL1. Our findings demonstrate proof-of-concept that U-DNA in tandem with recipient genome, can non-invasively infer relevant non-HLA loci/mismatches circumventing the need for the donor genomic DNA.
Source: Quantifying donor-recipient mismatches using recipient-derived sources of donor DNA