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Rheumatology Advance Access originally published online on May 20, 2009
Rheumatology 2009 48(7):755-760; doi:10.1093/rheumatology/kep074
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© The Author 2009. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Urinary FOXP3 mRNA in patients with lupus nephritis—relation with disease activity and treatment response

Gang Wang1, Fernand M.-M. Lai2, Lai-Shan Tam1, Edmund K.-M. Li1, Bonnie C.-H. Kwan1, Kai-Ming Chow1, Philip K.-T. Li1 and Cheuk-Chun Szeto1

1Department of Medicine and Therapeutics and 2Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong, China.

Correspondence to: Cheuk-Chun Szeto, Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, China. E-mail: ccszeto{at}cuhk.edu.hk


   Abstract

Objective. Regulatory T lymphocytes (Tregs) probably play an important role in the pathogenesis of SLE.

Methods. We quantified messenger RNA (mRNA) expression of FOXP3, a critical regulator for the development and function of Tregs, in the urinary sediment of 25 subjects with active lupus nephritis (LN), 17 with inactive lupus and 7 healthy subjects.

Results. We found that the expression level of FOXP3 was significantly higher in urine from patients with active LN than from subjects with inactive lupus and healthy controls (24.5 ± 45.8 vs 0.8 ± 1.0 vs 0.6 ± 0.8 copy; P < 0.001). In the active group, urinary FOXP3 mRNA expression level was higher in patients with proliferative LN than non-proliferative nephritis (34.6 ± 56.3 vs 2.7 ± 2.1 copy; P = 0.019). Urinary FOXP3 mRNA level significantly correlated with SLEDAI (r = 0.668; P < 0.001) and proteinuria (r = 0.414; P = 0.006). In the active group, urinary FOXP3 mRNA level also significantly correlated with histological activity index (r = 0.541; P = 0.009) and marginally with intra-renal FOXP3 mRNA level (r = 0.360; P = 0.08). Urinary FOXP3 mRNA in patients with no response to therapy was higher than those with partial response or complete response (57.6 ± 69.8 vs 2.4 ± 1.9 copies; P = 0.02).

Conclusion. We concluded that urinary FOXP3 mRNA is markedly up-regulated in patients with active LN, and the level of expression is closely correlated with the clinical and histological disease activity. A high urinary FOXP3 mRNA in LN predicts a poor therapeutic response. Measurement of FOXP3 mRNA in urine sediment may be a non-invasive biomarker for assessing the severity and risk stratification in LN.

KEY WORDS: SLE, Lupus nephritis, Cytokine

Submitted 22 December 2008; revised version accepted 9 March 2009.
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