Histologic analysis of renal leukocyte infiltration in antineutrophil cytoplasmic antibody–associated vasculitis: Importance of monocyte and neutrophil infiltration in tissue damage

Abstract

Objective. The histopathologic lesions in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) have been studied extensively, but the exact composition of the cellular infiltrate is unclear. We undertook this study to analyze renal leukocyte infiltration and the cellular distribution within glomeruli and interstitium in 65 renal biopsy samples obtained from patients newly diagnosed as having AAV.Methods. Renal cellular tissue infiltration was assessed with an immunoperoxidase method. Furthermore, the infiltrating cell types were correlated with clinical and histopathologic data.Results. The predominant interstitial infiltrating cells were T lymphocytes, while monocytes and, to a lesser extent, granulocytes constituted the dominant infiltrating cell types in glomeruli. Interestingly, lymphocyte infiltration was predominantly periglomerular, especially around glomeruli with sclerosis or heavy crescent formation, while interstitial monocyte and neutrophil infiltration was diffusely distributed over the interstitial tissue. A significant correlation was found for the glomerular infiltration of CD68-positive macrophages with the presence of glomerular necrosis as well as with the number of glomeruli with crescents (P < 0.0001 and P ‫؍‬ 0.005, respectively). No correlation was found for interstitial fibrosis with the infiltration of any leukocyte subset. Furthermore, a significant correlation was found for the interstitial as well as for the glomerular infiltration of CD68-positive macrophages with serum creatinine concentration at the time of biopsy (P ‫؍‬ 0.001 and P ‫؍‬ 0.006, respectively).Conclusion. These data underscore a major role of monocytes in addition to neutrophils in the tissue damage of AAV.

ANCAs Are Also Antimonocyte Cytoplasmic Autoantibodies

“…The results of the work by Zhao et al (13) are in accord with those reported in the work by Weidner et al (14), which also showed that monocytes/macrophages and to a lesser extent, neutrophils were the predominant leukocytes in glomeruli in renal biopsies from patients with ANCA GN, with 4.767.4 monocytes/macrophages compared with 3.267.4 neutrophils per glomerular cross-section (14). Neither study identified substantial numbers of T lymphocytes or B lymphocytes (13,14).…”

“…Neither study identified substantial numbers of T lymphocytes or B lymphocytes (13,14). This latter finding differs from the study by Cunningham et al (15), which reported 7.366.1 macrophages, 3.762.5 T lymphocytes, and 2.861.7 neutrophils per glomerular cross-section in patients with pauci-immune crescentic GN.…”

Tubular Lesions Predict Renal Outcome in Antineutrophil Cytoplasmic Antibody–Associated Glomerulonephritis after Rituximab Therapy

“…In the interstitium, CD3+ T cells have been described as the dominant cell type, with the balance between CD4+ helper T cells and CD8+ cytotoxic T cells shifted somewhat toward the latter. 26,27 Furthermore, interstitial T cells (CD3+ and CD8+) have been reported to correlate significantly with serum creatinine at the time of biopsy. 26,27 Our data add that both tubular intraepithelial B cells (markers CD79a and CD20) and tubular intraepithelial T cells are present in biopsies of AAV patients, but that only the latter are related to impaired renal function during follow-up in patients receiving B cell-depleting therapy.…”

CC Chemokine Ligand 18 in ANCA-Associated Crescentic GN

“…Studies in rodent models and humans have shown that T cells, macrophages, and DCs play a central role in the development and progression of proliferative and crescentic GN. 23,[25][26][27][28][29][30][31][32][33] Chemokines and their receptors have been identified as key regulators of directional leukocyte migration 12 and therefore, might be an interesting therapeutic target or biomarker in patients with ANCAassociated crescentic GN.…”