Transcriptomics

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Molecular patterns of isolated tubulitis differ from tubulitis with interstitial inflammation in early indication biopsies of kidney allografts


ABSTRACT: Banff 2019 update of kidney allograft pathology excluded isolated tubulitis without interstitial inflammation (ISO-T) from category of borderline (suspicious) for acute T cell-mediated rejection due to its proposed benign clinical outcome. However, molecular assessment of ISO-T has not been explored yet. ISO-T or interstitial inflammation with tubulitis (I+T) were diagnosed in indication biopsies within first 14 postoperative days. Molecular patterns of ISO-T was compared to I+T either by using RNA sequencing (n=16) or by Molecular Microscope Diagnostic System (MMDx, n=51). In ISO-T group, RNA sequencing showed lower expression of genes related to interferon-y (p=1.5 *10-16), cytokine signaling (p=2.1 *10-20) and inflammatory response (p=1.0*10-13) than in I+T groups. Increased transcripts in I+T group had significant overlap with previously described pathogenesis-based transcript sets associated with T cell-mediated rejection (TCMR), cytotoxic and effector T cell transcripts. In ISO-T, MMDx classified biopsies as no-rejection in 25/32 (78%) while in I+T in 12/19 (63%). ISO-T had significantly lower MMDx scores for interstitial inflammation (p=0.014), tubulitis (p=0.035) and TCMR (p=0.016) compared to I+T. Less inflammatory molecular signals of isolated tubulitis suggest its benign phenotype also on molecular level.

ORGANISM(S): Homo sapiens

PROVIDER: GSE161705 | GEO | 2020/11/19

REPOSITORIES: GEO

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