Background Kidney transplantation significantly improves the quality of life and survival in ESKD. Despite advancements in immunosuppressive therapies reducing acute rejection rates, chronic graft outcomes remain suboptimal. Transplant glomerulopathy (TG), a hallmark of chronic allograft injury (CAI), majorly contributes to graft dysfunction. It arises from endothelial injury associated with antibody-mediated rejection (ABMR), T-cell-mediated rejection (TCMR), thrombotic microangiopathy, and infection, notably Hepatitis C infection. However, there is limited data on immune cell infiltrates and their role in TG pathogenesis. This study investigates the etiologies of TG and characterizes the types, distribution, and clinical relevance of immune cell infiltrates in renal allograft biopsies. Materials and Methods We analyzed 80 renal allograft biopsies with histologically confirmed TG. Dual- and single-color immunohistochemistry was performed for CD3, CD20, CD4, CD8, CD68, CD163, and CD56. Results Of the 80 cases, 49% were attributed to ABMR, 12.5% to TCMR, 15% had a prior documented hepatitis C infection, 10% showed immune complex deposits, 12.5% showed mixed ABMR and TCMR features, and 12.5% remained unclassified. M2 macrophages (CD163 + ) and CD8 + cytotoxic cells were predominant in glomeruli and the tubulointerstitial compartment, showing a macrophage and T- and B-lymphocytes admixture. Macrophage infiltration correlated with chronic injury markers, including interstitial fibrosis and tubular atrophy. Natural killer (NK) cells were minimally involved. Conclusion TG is driven by multifactorial mechanisms, with M2 macrophages and CD8 + T-cells dominant in the glomeruli and tubulointerstitial compartments. Interventions targeting the depletion of specific immune cell subsets may mitigate CAI and enhance graft survival.
Gopalakrishna et al. (Thu,) studied this question.
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