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

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. Overall design: To compare expression profiles of kidney allografts between isolated tubulitis without interstitial inflammation (ISO-T) and interstitial inflammation with tubulitis (I+T) by RNAseq.