Background/Purpose: In addition to the effector roles of classically activated macrophages for tissue injury, recent studies have shown that alternatively activated (M2) macrophages are involved in resolution of inflammation in animal models of kidney disease. But, clinical relevance of M2 macrophage in human disease is largely unknown. The current study aimed to evaluate renal accumulation of macrophage phenotypes in human lupus nephritis (LN) and significance of soluble form of CD163 (sCD163), a representative marker for M2 cells, for LN disease activity.

Methods: Plasma, urine and kidney biopsy samples were obtained from 74 patients with LN. Histological features were classified according to the ISN/RPS LN criteria. Immunohistochemical analyses using anti-human CD68, CD163 or CD204 antibodies were performed for identification of macrophage phenotypes. Concentrations sCD163 and MCP-1 in plasma and urine were measured by ELISA.

Results: Immunohistological analysis in LN glomeluli revealed more than 70% of CD68⁺ macrophages was merged with CD163⁺ cells and more than 90% of CD163⁺ cells was merged with CD68⁺ cells. However, CD163⁺ cells appeared to be more than CD68⁺ cells in interstitum, indicating the different origin of glomerular and interstitial CD163⁺ macophages. The cell counts of glomerular CD68⁺, CD163⁺ or CD204⁺ macrophages were increased in association with severity of biopsy active index (BAI) score in LN. Interstitial CD68⁺, CD163⁺ or CD204⁺macrophage infiltration correlated with eGFR. Urine sCD163 level showed stronger correlation with the number of glomerular CD163 positive cell counts (r=0.501) and BAI score (r=0.644) than plasma sCD163 levels with both of the above (r=0.289 and r=0.295, respectively). Correlation of urine sCD163 with BAI was comparable to that of urine MCP-1 levels (r=0.592) and was much better than NGAL (r=0.174) in LN.

Conclusion: These results suggest that CD163⁺ or CD204⁺ macrophage is the dominant phenotype in kidneys of LN patients, and urine sCD163 level has a potential significance for estimation of disease activity in human LN.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/association-of-glomerular-macrophage-phenotypes-and-urine-soluble-cd163-with-disease-activity-in-human-lupus-nephritis/