The gene expression of type 17 T-helper cell-related cytokines in the urinary sediment of patients with systemic lupus erythematosus.
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.
Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, China.
Bonnie Ching-Ha
BC
Kwan
Lai-Shan
LS
Tam
Ka-Bik
KB
Lai
Fernand Mac-Moune
FM
Lai
Edmund Kwok-Ming
EK
Li
Gang
G
Wang
Kai-Ming
KM
Chow
Philip Kam-Tao
PK
Li
Cheuk-Chun
CC
Szeto
D000328:Adult; D016207:Cytokines / Q000235:genetics / Q000652:urine*; D005260:Female; D005500:Follow-Up Studies; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008181:Lupus Nephritis / Q000276:immunology; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics; D012720:Severity of Illness Index; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D016207:Cytokines; D012333:RNA, Messenger