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C4d-Negative ABMR Banff Recognition — ESENeph MCQ

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HardTransplantationC4d-Negative ABMR Banff RecognitionESENeph

A 39-year-old man with a kidney transplant presents with progressive decline in eGFR from 55 to 35 mL/min/1.73m2 over 2 years. Biopsy shows C4d-negative, microvascular inflammation with glomerulitis (g2) and peritubular capillaritis (ptc2). DSA testing shows persistent class II DSA. What does C4d-negative microvascular inflammation with DSA represent?

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Correct answer: B — C4d-negative antibody-mediated rejection — now recognised in Banff classification

The Banff 2013 and 2019 updates formally recognised C4d-negative antibody-mediated rejection (ABMR). Previously, C4d positivity was required for ABMR diagnosis. However, ~40-50% of ABMR cases are C4d-negative because C4d deposition is a snapshot marker that may be absent during active endothelial injury. The Banff criteria now accept either C4d positivity OR evidence of gene expression classifiers (molecular AMR) as evidence of complement activation. Microvascular inflammation (glomerulitis + peritubular capillaritis scores ≥2) with circulating DSA fulfils criteria for ABMR regardless of C4d status. This recognition was critical because C4d-negative ABMR was previously underdiagnosed.

Reference: Banff 2019 – Kidney Allograft Pathology; Loupy et al 2017 – C4d-Negative ABMR