Renal Acute Cellular Rejection: Correlation Between the Immunophenotype and Cytokine Expression of the Inflammatory Cells in Acute Glomerulitis, Arterial Intimitis, and Tubulointerstitial Nephritis

Abstract

Background Acute renal transplant glomerulopathy (ARTG) refers to a glomerular inflammation mainly within the three 1st months posttransplantation, characterized by the influx of lymphomononuclear cells and swelling of endothelial and mesangial cells. The reported occurrence of ARTG is between 4.3% and 14% of all renal allografts. Investigations on the pathogenesis and on the impact on graft survival have been critically reviewed. The simultaneous occurrence of ARTG and acute vascular rejection (AVR) is common. However, cases of ARTG with no vascular inflammation suggest distinct pathogenic mechanisms for the entities. The objective of the present work was to compare the immunophenotype of the infiltrating cells and the cytokine immunoexpression (ICE) in ARTG with those of arterial intimal inflammation in AVR. We also compared the glomerular ICE with that in acute tubulointerstitial rejection and in arterial intimal inflammation. Methods Forty kidney transplant biopsy specimens were allocated to 4 groups: 10 cases of acute tubular necrosis without ARTG or AVR (group I, Control); 10 cases of ARTG without AVR (group II); 10 cases of ARTG with AVR (group III); and 10 cases of AVR without ARTG (group IV). Results The immunoexpressions of CD68 (macrophages), CD8 (cytotoxic T lymphocyte), CD4 (helper T lymphocyte), CD20 (B lymphocyte), S100 protein (antigen-presenting cells), interleukin (IL)-4, IL-10, and interferon (INF)-γ–positive cells were evaluated in the glomeruli, arterial intima, and tubulointerstitium. In the comparative study between ARTG and arterial intimal inflammation, CD68+ cells predominated in the ARTG and T CD8+ cells in inflammation; the cytokine patterns were similar in both cases (IL-4 predominance). Conclusions Altogether, the data suggested similar pathogenic mechanisms, with mild sequential differences, for the glomerulitis, intimitis, and tubulointerstitial inflammation in cellular acute rejection. These findings seem to confirm the immunological nature of ARTG, indicating that ARTG might be included in the Banff classification as an additional parameter for acute rejection.