A kidney transplant recipient develops gradual graft dysfunction with proteinuria 3 years post-transplant. Biopsy shows 'double contour' appearance of glomerular basement membranes and C4d deposits in peritubular capillaries. What is the predominant mechanism of rejection?
- A Acute cellular rejection mediated by cytotoxic T lymphocytes
- B Hyperacute rejection mediated by pre-formed anti-HLA antibodies
- C Chronic humoral (antibody-mediated) rejection with donor-specific antibodies ✓
- D Calcineurin inhibitor nephrotoxicity causing interstitial fibrosis
Explanation
The classic features described — late onset (years), proteinuria, glomerular basement membrane duplication ('tram-track' or 'double contour'), and C4d deposits in peritubular capillaries — are hallmarks of chronic antibody-mediated rejection (cAMR). C4d is a breakdown product of complement activation by donor-specific antibodies (DSA) binding to endothelial antigens. Unlike hyperacute rejection (which occurs within minutes of anastomosis) or acute cellular rejection (marked by tubulointerstitial infiltration), cAMR results from slowly developing DSA and complement activation over months to years, progressively destroying the graft vasculature.
Reference: Ananthanarayan & Paniker's Textbook of Microbiology, 11th ed.
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Written and medically reviewed by the StethoPrep medical team.