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Monitoring urinary levels of monocyte chemotactic and activating factor reflects disease activity of lupus nephritis
1First Department of Internal Medicine, School of Medicine, Kanazawa University, Japan.
Abstract:
Monocytes/macrophages (M phi) have been implicated in the pathogenesis of lupus nephritis (LN), but the precise molecular mechanism of recruitment and activation of M phi in LN remains unclear. To clarify the involvement of chemotactic cytokines (chemokines) in those events, we measured levels of monocyte chemotactic and activating factor (MCAF, also termed monocyte chemoattractant protein-1, MCP-1) in urines and sera derived from 42 patients with LN. Both urinary and serum MCAF levels were significantly higher in patients with LN as compared with 22 healthy volunteers (10.3 +/- 3.2 vs. 1.0 +/- 0.1 pg/ml . creatinine, 212.2 +/- 75.8 vs. 66.1 +/- 15.5 pg/ml, respectively, P < 0.05, mean +/- SEM). Histological examination of renal lesions from 41 patients classified 19 as active according to the WHO-defined classes IIIb, IVb and IVc, and 22 as inactive by the WHO-defined classes I, II, IIIc, IVd and V. Urinary MCAF levels in the patients with active lesions were significantly higher than those with inactive lesions (20.3 +/- 6.4 vs. 1.7 +/- 0.3 pg/ml . creatinine, P < 0.01). Moreover, elevated urinary MCAF levels were dramatically decreased during steroid therapy-induced convalescence in 29 patients examined serially (13.9 +/- 4.5 vs. 5.3 +/- 1.7 pg/ml . creatinine, P < 0.001), whereas serum MCAF levels did not change significantly. Endothelial cells, renal epithelial cells and infiltrating mononuclear cells in the tubulointerstitial regions were MCAF-positive in immunohistochemical as well as in situ hybridization analysis. These observations suggest that MCAF is probably involved in the pathogenesis of LN with active lesions, possibly through the recruitment and activation of M phi, and that measurement of urinary MCAF levels may be a useful clinical tool for monitoring the disease activity of LN.
Insights
Urinary monocyte chemotactic and activating factor (MCAF) levels are elevated in lupus nephritis (LN) patients with active disease. Urinary MCAF may serve as a biomarker for monitoring LN activity and guiding treatment.
Area of Science:
- Nephrology
- Immunology
- Molecular Biology
Background:
- Monocytes/macrophages (M phi) play a role in lupus nephritis (LN) pathogenesis.
- The specific molecular mechanisms of M phi recruitment and activation in LN are not fully understood.
Purpose of the Study:
- To investigate the role of chemotactic cytokines, specifically monocyte chemotactic and activating factor (MCAF), in LN.
- To determine if MCAF levels correlate with disease activity and treatment response in LN patients.
Main Methods:
- MCAF levels were measured in urine and serum samples from 42 LN patients and 22 healthy controls.
- Renal biopsy histology was used to classify LN lesions as active or inactive.
- Immunohistochemistry and in situ hybridization were performed on renal tissue.
Main Results:
- Urinary and serum MCAF levels were significantly higher in LN patients compared to healthy controls.
- Urinary MCAF levels were significantly higher in patients with active LN lesions than in those with inactive lesions.
- Elevated urinary MCAF levels decreased significantly during steroid therapy-induced remission, while serum levels did not change significantly.
Conclusions:
- MCAF is likely involved in the pathogenesis of active LN, potentially by recruiting and activating M phi.
- Urinary MCAF levels may be a valuable clinical biomarker for assessing LN disease activity and response to treatment.