Urinary FOXP3 mRNA in patients with lupus nephritis--relation with disease activity and treatment response.
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).


CONCLUSIONS
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.
Wang
Gang
G
Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, China.
Lai
Fernand M-M
FM
Tam
Lai-Shan
LS
Li
Edmund K-M
EK
Kwan
Bonnie C-H
BC
Chow
Kai-Ming
KM
Li
Philip K-T
PK
Szeto
Cheuk-Chun
CC
D000208:Acute Disease; D000328:Adult; D015415:Biomarkers / Q000652:urine; D016022:Case-Control Studies; D005260:Female; D005500:Follow-Up Studies; D051858:Forkhead Transcription Factors / Q000235:genetics*; D015870:Gene Expression; D006801:Humans; D007668:Kidney / Q000473:pathology; D008180:Lupus Erythematosus, Systemic / Q000652:urine; D008181:Lupus Nephritis / Q000473:pathology / Q000652:urine*; D008297:Male; D008875:Middle Aged; D011507:Proteinuria; D012333:RNA, Messenger / Q000652:urine*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D018709:Statistics, Nonparametric; D015854:Up-Regulation
D015415:Biomarkers; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D012333:RNA, Messenger