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Rheumatology Advance Access originally published online on September 22, 2009
Rheumatology 2009 48(12):1491-1497; doi:10.1093/rheumatology/kep255
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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

The gene expression of type 17 T-helper cell-related cytokines in the urinary sediment of patients with systemic lupus erythematosus

Bonnie Ching-Ha Kwan1, Lai-Shan Tam1, Ka-Bik Lai1, Fernand Mac-Moune Lai2, Edmund Kwok-Ming Li1, Gang Wang1, Kai-Ming Chow1, Philip Kam-Tao 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. We studied the role of type 17 Th cells (TH17) in the pathogenesis of SLE.

Methods. We quantified the mRNA expression of IL-17, -23, -27 and retinoic-acid-related orphan receptor (ROR)-{gamma}, the regulator for the development and function of TH17, in the urinary sediment of 23 subjects with active lupus nephritis, 25 subjects with a history of lupus nephritis in remission, 30 SLE patients with no history of renal involvement and 8 healthy subjects.

Results. All three groups of lupus patients had a higher urinary expression of TH17-related cytokines than the controls. However, urinary expression of IL-17 and -27 was found to be inversely correlated with the SLEDAI score (r = –0.252 and –0.258, respectively; P < 0.05 for both). For patients with active lupus nephritis, the histological activity index of kidney biopsy was also found to be inversely correlated with the urinary expression of ROR-{gamma} (r = –0.447; P = 0.032), IL-17 (r = –0.454; P = 0.029) and IL-23 (r = –0.455; P = 0.029). Urinary expression of IL-17, -23, -27 and ROR was also found to be inversely correlated with the urinary expression of IFN-{gamma} and T-bet, the key transcription factor of type 1 Th cells. After 6 months of treatment, urinary IL-27 expression rose significantly in patients with complete response (from 2.07 ± 1.62 to 3.70 ± 1.69; P = 0.028) but remained unchanged in those with partial or no response (from 2.60 ± 1.87 to 2.52 ± 1.94; P = 0.9).

Conclusions. The urinary expression of TH17-related genes is increased in SLE patients. The degree of up-regulation, however, is inversely related to systemic and renal lupus activity, as well as urinary expression of TH1-related genes. Urinary expression of TH17-related genes increased again after successful immunosuppressive treatment of active disease. Our findings suggest a regulatory role of TH17-related cytokines in pathogenesis of lupus nephritis.

KEY WORDS: SLE, Lupus nephritis, Cytokine

Submitted 20 May 2009; revised version accepted 20 July 2009.
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