Intragraft FOXP3+ Cells and Continuous Banff Indices in T Cell-Mediated Kidney Allograft Rejection

Background and Objectives: FOXP3+ (Forkhead box P3) regulatory T cells contribute to immune tolerance after kidney transplantation, but their role in T cell-mediated rejection (TCMR) remains controversial. This study investigated the association between intragraft FOXP3+ cells and the recently introduced Banff-derived activity (AI) and chronicity index (CI) in biopsy-proven TCMR. Materials and Methods: This retrospective cross-sectional study included 119 kidney allograft biopsies diagnosed as acute or chronic active TCMR according to the Banff classification. FOXP3+ cells were assessed by immunohistochemistry and expressed as cortical cell density (cells/mm2). Associations between FOXP3+ cell density, Banff-derived indices, inflammatory cell densities, and clinical parameters were analyzed using non-parametric statistical methods. Results: FOXP3+ cells were detected in 17.6% of biopsies. FOXP3+ cell density was univariately associated with higher CI values (ρ = 0.228, p = 0.013) and chronic lesions interstitial fibrosis (ci) (ρ = 0.284, p = 0.002) and tubular atrophy (ct) (ρ = 0.246, p = 0.008). No association was observed with AI or activity lesions, except for a weak negative correlation with interstitial inflammation (i) (ρ = −0.209, p = 0.025). In multivariable analysis, FOXP3 positivity was not significantly associated with CI after adjustment for transplantation–biopsy interval (B = 0.568, 95% CI −0.741–1.876, p = 0.391). FOXP3+ cell density positively correlated with cluster of diferentiation (CD)4+ (ρ = 0.350, p < 0.001), CD8+ (ρ = 0.229, p = 0.018), and CD163+ (ρ = 0.207, p = 0.047) cell densities. No association with short-term graft outcome was observed. Conclusions: FOXP3+ cell infiltration was associated with chronic histological changes in unadjusted analyses, but this association did not remain statistically significant after adjustment for transplantation-to-biopsy interval. These preliminary findings suggest that FOXP3+ cell accumulation and chronic histological changes may represent parallel time-dependent phenomena and require confirmation in larger cohorts.

Authors

Institutions

Publication Details

Journal
Medicina
Published
2026-09-10
DOI
https://doi.org/10.3390/medicina62091746
Primary Topic
T-cell and B-cell Immunology
Type
article
Field-Weighted Citation Impact
0.00
Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
article

Intragraft FOXP3+ Cells and Continuous Banff Indices in T Cell-Mediated Kidney Allograft Rejection

Merica Glavina Durdov, Lada Zibar, Ana Dunatov Huljev, Sandra Zekić Tomaš et al.
Medicina
T-cell and B-cell Immunology
article

Intragraft FOXP3+ Cells and Continuous Banff Indices in T Cell-Mediated Kidney Allograft Rejection

Merica Glavina Durdov, Lada Zibar, Ana Dunatov Huljev, Sandra Zekić Tomaš, Danica Galešić Ljubanović, Petar Šenjug, Petar Đolonga, Anja Stadnik
article en

Abstract

Background and Objectives: FOXP3+ (Forkhead box P3) regulatory T cells contribute to immune tolerance after kidney transplantation, but their role in T cell-mediated rejection (TCMR) remains controversial. This study investigated the association between intragraft FOXP3+ cells and the recently introduced Banff-derived activity (AI) and chronicity index (CI) in biopsy-proven TCMR. Materials and Methods: This retrospective cross-sectional study included 119 kidney allograft biopsies diagnosed as acute or chronic active TCMR according to the Banff classification. FOXP3+ cells were assessed by immunohistochemistry and expressed as cortical cell density (cells/mm2). Associations between FOXP3+ cell density, Banff-derived indices, inflammatory cell densities, and clinical parameters were analyzed using non-parametric statistical methods. Results: FOXP3+ cells were detected in 17.6% of biopsies. FOXP3+ cell density was univariately associated with higher CI values (ρ = 0.228, p = 0.013) and chronic lesions interstitial fibrosis (ci) (ρ = 0.284, p = 0.002) and tubular atrophy (ct) (ρ = 0.246, p = 0.008). No association was observed with AI or activity lesions, except for a weak negative correlation with interstitial inflammation (i) (ρ = −0.209, p = 0.025). In multivariable analysis, FOXP3 positivity was not significantly associated with CI after adjustment for transplantation–biopsy interval (B = 0.568, 95% CI −0.741–1.876, p = 0.391). FOXP3+ cell density positively correlated with cluster of diferentiation (CD)4+ (ρ = 0.350, p < 0.001), CD8+ (ρ = 0.229, p = 0.018), and CD163+ (ρ = 0.207, p = 0.047) cell densities. No association with short-term graft outcome was observed. Conclusions: FOXP3+ cell infiltration was associated with chronic histological changes in unadjusted analyses, but this association did not remain statistically significant after adjustment for transplantation-to-biopsy interval. These preliminary findings suggest that FOXP3+ cell accumulation and chronic histological changes may represent parallel time-dependent phenomena and require confirmation in larger cohorts.

MedicinaVol. 62(9)
University of Zagreb (HR), University Hospital Dubrava (HR), Klinička bolnica Merkur (HR), University of Osijek (HR), University of Split (HR)
Good health and well-being
Openalex Percentile: Top 17%
T-cell and B-cell Immunology
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.