*Purpose: Borderline T cell-mediated rejection (BR) is associated with inferior outcomes. In the multicenter CTOT-04 study, we discovered and validated a urinary cell three-gene signature of CD3ε mRNA, IP-10 mRNA and 18s rRNA diagnostic of TCMR (Suthanthiran et al. N Engl J Med, 2013). We investigated whether the urinary cell three-gene signature is diagnostic of BR.

*Methods: Urinary cell mRNAs were measured in 377 biopsy-matched urine samples from 300 kidney transplant recipients. Interstitial inflammation (i) and tubulitis (t) were scored using Banff criteria. Diagnosis of BR based on i1, t1, i2, t1, or i1, t2 and TCMR= i≥2, t≥2 (Loupy et al. Am J Transplant,2020). Exclusion criteria: inadequate biopsy; BKVN; urinary BKV-VP1 mRNA level diagnostic of BKVN (Dadhania et al. Transplantation,2010), i1 or t1 alone. RNA was isolated from urinary cell pellets, absolute transcript levels measured by customized RT-qPCR, and the CTOT-04 signature score computed.

*Results: 293 biopsies were included (Table 1). CTOT-04 signature distinguished i0, t0 biopsies from BR and TCMR (p<0.0001, ANOVA) (Fig.1A). 18S normalized CD3ε and IP-10 mRNAs elevated in BR and TCMR urine (Fig.1D-E). Accurate diagnosis of BR and TCMR shown (Table 2A-B).

*Conclusions: Urinary-cell CTOT-04 signature discriminates i0, t0 biopsies from BR or TCMR biopsies. Our findings may help decrease biopsies performed to diagnose BR or TCMR and prognosticate graft outcome.

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