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Enhanced Diagnosis of Chronic Antibody-mediated Rejection Using Peritubular Capillary Multilayering
Brian J Nankivell1, Meena Shingde2, Chow Heok P'Ng2
1Department of Renal Medicine, Tissue Pathology and Diagnostic Oncology and Electron Microscopy Units, NSW Health Pathology, Sydney, NSW, Australia.
Transplantation
|October 9, 2025
Summary
Peritubular capillary multilayering (PTCML) is a key marker for chronic antibody-mediated rejection (AMR). New criteria using circumferential scoring of PTCML show high sensitivity for detecting early chronic AMR, improving upon existing diagnostic methods.
Area of Science:
- Nephrology
- Transplant Immunology
- Histopathology
Background:
- Peritubular capillary multilayering (PTCML) is an ultrastructural feature of chronic antibody-mediated rejection (AMR).
- Current diagnostic thresholds for PTCML in chronic AMR are uncertain.
- Understanding PTCML is crucial for accurate diagnosis and patient management.
Purpose of the Study:
- To evaluate the relationship between PTCML and chronic AMR in kidney transplant recipients.
- To establish diagnostic thresholds for PTCML indicative of chronic AMR.
- To assess the diagnostic performance of novel PTCML criteria compared to existing Banff criteria.
Main Methods:
- A single-center, prospective cohort study involving 2541 kidney samples from 1195 recipients.
- Epidemiological modeling to identify clinical risk factors for abnormal PTCML scores.
- Histological analysis using Banff criteria and novel PTCML scoring methods, including circumferential assessment.
Main Results:
- Clinical risk factors for abnormal PTCML (≥3) included younger recipients, living donation, early AMR, and higher donor-specific antibody strength.
- PTCML layers correlated with transplant time, AMR histology, DSA, renal dysfunction, proteinuria, and graft failure.
- Modified PTCML criteria (≥7 or 2×PTCML ≥5) improved sensitivity for diagnosing chronic AMR compared to Banff 2013 criteria.
Conclusions:
- Circumferential PTCML (≥3) in multiple capillaries is a sensitive histological marker for mild chronic AMR and tissue injury.
- The proposed ultrastructural criteria offer a superior method for detecting early chronic AMR phenotypes.
- Multicenter validation of these novel diagnostic criteria is recommended.
