Rheumatology Advance Access published online on September 22, 2009
Rheumatology, doi:10.1093/rheumatology/kep255
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The gene expression of type 17 T-helper cell-related cytokines in the urinary sediment of patients with systemic lupus erythematosus
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
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Abstract |
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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)-
, 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- (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- 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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