Abstract
Background. Endothelial C4d deposition is used as a reliable marker to diagnose antibody-mediated rejection (AMR) in renal and cardiac transplantation, but remains controversial in lung transplantation.
Objectives. This study was planned to study the utility of C4d by immunohistochemistry (IHC) for the diagnosis of AMR in lung allograft transbronchial biopsies (TBBx).
Methods. We evaluated C4d staining by IHC in a blinded fashion, on 158 consecutive formalin-fixed paraffin embedded (FFPE) TBBx, from a cohort of 48 lung transplant recipients. Capillary C4d staining was scored as 0, 1 (<10% of capillaries), 2 (10% to 50% capillaries) or 3 (>50% capillaries). C4d scoring was compared with microvascular inflammation (MI), acute lung injury (ALI), acute cellular rejection (ACR), concomitant donor specific antibodies (DSA) and graft dysfunction.
Results. C4d3, C4d2, C4d1 and C4d0 occurred in 4 (2.5%), 6 (3.8%), 28 (17.7%) and 120 (75.9%) TBBx, respectively. Capillary staining ≥C4d2 was significantly associated with MI (50% vs 7.4%; p=0.001). C4d3 occurred more frequently with DSA (5.5% in DSA group vs 1.5% in non-DSA group) and was significantly associated with graft dysfunction (p=0.03). Histopathologic findings alone did not correlate with DSA. Three out of 4 patients with C4d3 developed bronchiolitis obliterans syndrome (BOS).
Conclusions. Diffuse C4d deposition in endothelial capillaries was correlated with MI and graft dysfunction. It was closely related, but not significantly, with DSA and development of BOS in lung transplant recipients. Diffuse C4d deposition in the lung might be a specific marker for AMR, although lacking sensitivity.
- Copyright ©the authors 2016