Figure 9. The Treg gene signature as a predictive biomarker of C-peptide decline in T1D subjects treated with ustekinumab.

Adult new-onset T1D patients were treated with ustekinumab, as outlined in the CONSORT flow diagram in Supplemental Figure 3. (A) C-peptide was quantified (2h AUC MMTT) at baseline (M0), 1 month (M1), and 12 months (M12), and absolute change in C-peptide from M0 to M12 was calculated. Subjects were divided into those with slow (n = 11) or rapid (n = 5) decline based on the absolute decline at M12, with slow subjects defined as those who lost less than 0.3 pmol C-peptide/year. (B–E) The TGS was measured in sorted CD25^hiCD127^lo Tregs or PBMCs from M0 and M9 samples. (B) Test details when the algorithm from Figure 8B was applied to M0 Treg data. (C) Treg-based algorithm and biomarker scores for slow versus rapid C-peptide decline using relative TGS data (M9/M0 prior to log₂ transformation). (D) Treg- and (E) PBMC-based algorithm and biomarker scores using M9 TGS expression data. Horizontal lines in C–E represent means, with SD represented by error bars; dashed horizontal lines represent cutoffs for sensitivity and specificity calculations. (F) Summary of gene usage in C-peptide decline algorithms described in B–E.