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1006 Evaluation of intra-renal plasmacytoid dendritic cells in active lupus nephritis
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1006 Evaluation of intra-renal plasmacytoid dendritic cells in active lupus nephritis
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Journal Article
1006 Evaluation of intra-renal plasmacytoid dendritic cells in active lupus nephritis
2024
Overview
Interferon-alpha (IFNα)-responsive gene expression is highly upregulated in the kidneys of patients with active lupus nephritis (LN). Infiltrating plasmacytoid dendritic cells (pDCs) have been postulated to be a source of intrarenal IFNα. In this study we quantified intrarenal pDCs in patients with LN and correlated infiltration with histologic activity and chronicity.Immunohistochemistry (IHC) for BDCA-2, a marker of pDCs and a subset of dendritic cells was used to visualize intrarenal pDCs. All pDCs within a biopsy were counted and the average number of glomerular pDCs and the number of tubulointerstitial pDCs per unit area were determined. The NIH activity and chronicity indices were calculated. IHC for MX1, an IFNα-inducible protein was used to characterize the interferon response.We studied 18 patients with proliferative (70% (n=12)) or proliferative + membranous LN (30%, n=6), 60% (n=11) of whom were de novo diagnoses and 40% (n=7) carried an LN diagnosis for 1–6 years. Patients were biopsied for suspected LN flare. pDCs were found mainly as individual cells within the tubulointerstitium in these kidney biopsies, and were seldom seen within glomeruli. In some biopsies, aggregations of pDCs were found in areas of tubulointerstitial inflammation or surrounding glomeruli. A median (range) of 0 (0–0.82) pDCs/glomerulus and 2.7 (0.77–49) pDC/mm2 of tubulointerstitium were found. There was no evidence of an association between tubulointerstitial pDCs and serum creatinine, proteinuria, activity index, or chronicity index. MX1 immunoreactivity was found in abundance throughout the kidney, including glomerular and tubular epithelial cells, glomerular and tubulointerstitial endothelial cells, vascular wall smooth muscle cells, and infiltrating inflammatory cells. pDCs are thought to be the major source of IFNα in the kidneys of patients with LN. If this is true, our data suggest that very few infiltrating pDCs are needed to initiate a robust IFNα response within the kidneys.
Publisher
Lupus Foundation of America,BMJ Publishing Group LTD,BMJ Publishing Group
Subject
