Imbalance of Th1/Th2 transcription factors in patients with lupus nephritis.
OBJECTIVE
Systemic lupus erythematosus (SLE) is characterized by the aberrant activation of T lymphocytes. Since T-bet and GATA-3 are the principal transcription factors for the differentiation of type-1 and type-2 helper T lymphocytes, respectively, we studied their mRNA expression in the urinary sediment of SLE patients and compared this with their urinary and intra-renal protein expression.


METHODS
We studied 100 SLE patients and 10 healthy subjects. Urinary mRNA expression of T-bet and GATA-3 were studied by the real-time quantitative polymerase chain reaction. Intra-renal and urinary expressions of T-bet and GATA-3 were studied by immunohistochemistry and western blotting, respectively.


RESULTS
The urinary mRNA and protein expressions of T-bet were significantly higher in SLE patients with active nephritis than those with inactive disease (mRNA: P < 0.001; protein: P = 0.004). The urinary mRNA expression of T-bet correlated with the SLE disease activity index (SLEDAI) score (r = 0.55, P < 0.001) and the histological activity index (r = 0.48, P = 0.03). On the other hand, the urinary mRNA and protein expressions of GATA-3 were significantly lower in SLE patients with active nephritis (mRNA: P < 0.001; protein: P = 0.006), and GATA-3 mRNA expression inversely correlated with the SLEDAI score (r = 0.38, P < 0.001). For the 22 SLE patients with kidney biopsy, tubular expressions of T-bet and GATA-3 significantly correlated with the histological activity index (T-bet: r = 0.57, P = 0.006; GATA-3: r = -0.79, P < 0.001).


CONCLUSIONS
Patients with active lupus nephritis have increased T-bet and depressed GATA-3 expression in the urinary sediment and kidney tissue, indicating a predominant Th1 type of T-lymphocyte activation.
Chan
R W-Y
RW
Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, China.
Lai
F M-M
FM
Li
E K-M
EK
Tam
L-S
LS
Chow
K-M
KM
Li
P K-T
PK
Szeto
C-C
CC
D000328:Adult; D015415:Biomarkers / Q000378:metabolism / Q000652:urine; D015153:Blotting, Western / Q000379:methods; D005260:Female; D050990:GATA3 Transcription Factor / Q000235:genetics / Q000378:metabolism* / Q000652:urine; D015870:Gene Expression; D006801:Humans; D007668:Kidney / Q000378:metabolism; D008181:Lupus Nephritis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics; D012720:Severity of Illness Index; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism* / Q000652:urine; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D000098815:T-bet Transcription Factor
D015415:Biomarkers; D050990:GATA3 Transcription Factor; D012333:RNA, Messenger; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor