Figure 4.

Prospective trajectories of 18S rRNA normalized FOXP3 mRNA level and CTOT-04 3-gene TCMR diagnostic signature score as a function of time since TCMR biopsy. The loess-smoothed average within-person trajectories and 95% confidence bands of the urinary cell log₁₀-transformed, 18S rRNA normalized FOXP3 mRNA level and the median score of CTOT-04 3-gene TCMR diagnostic signature are shown for the reversible TCMR group (A, C) and the nonreversible TCMR group (B, D). Levels of mRNA in 81 urines from 21 patients with reversible TCMR and 43 urines from 12 patients with nonreversible TCMR were used to generate the prospective trajectories. (A) The median level of urinary cell FOXP3 mRNA at the time of TCMR biopsy was significantly higher in patients with reversible TCMR than in patients with nonreversible TCMR. The prospective trajectory in the reversible TCMR group started above the −1.33 threshold (for discriminating reversible from nonreversible TCMR) at time of TCMR biopsy and remained close to the threshold throughout the 30 days after the biopsy. (B) The prospective trajectory in patients with nonreversible TCMR started below the threshold at time of TCMR biopsy and remained well below the threshold through 30 days after the biopsy. (C) The prospective trajectory of the CTOT-04 3-gene TCMR diagnostic signature at time of TCMR biopsy did not differ significantly between those with reversible TCMR or nonreversible TCMR. Among the patients with reversible TCMR, the average score decreased from time of TCMR biopsy and crossed the diagnostic threshold of −1.213 within 15 days of initiation of antirejection therapy. (D) The CTOT-04 3-gene TCMR diagnostic signature prospective trajectory remained consistently above the threshold among the patients with nonreversible TCMR.