Molecular Rejection Signatures in Pancreas Transplant Biopsies

Biopsies were analyzed using a kidney-derived Molecular Microscope® Diagnostic System (MMDx) classifier, and molecular classifications were compared with histology and related to pancreas graft survival. MMDx classified 93 biopsies (75%) as no rejection, 13 (10%) as subthreshold rejection, and 18 (15%) as rejection, whereas histology identified rejection in 65 of 112 biopsies (58%) and 25 (22%) as indeterminate cases.

Concordance between histology and MMDx was low (Cohen’s κ = 0.14, p<0.001). Acute cellular histologic grading correlated strongly with multiple molecular scores, including interstitial inflammation (ρ=0.60, p=3.4×10⁻12), TCMR (ρ=0.55, p<3.2×10⁻10), acute kidney injury (ρ=0.48, p=7.4×10⁻8), and overall inflammation (ρ=0.46, p=4.4×10⁻7). Both subthreshold rejection (HR=4.41, 95% CI 1.29–15.1, p=0.018) and MMDx-defined rejection (HR=6.52, 95% CI 2.36–18.03, p=0.0003) were associated with significantly worse three-year graft survival compared to no rejection, whereas histologic classification showed no significant prognostic impact.