Elevated gene expression of Th1/Th2 associated transcription factors is correlated with disease activity in patients with systemic lupus erythematosus.
OBJECTIVE
T-box expressed in T cells (T-bet) and GATA-binding protein 3 (GATA-3) are transcriptional factors that play a crucial role in Th1 and Th2 development. We investigated the immunomodulatory roles of T-bet and GATA-3 and Th1/Th2 related cytokines in the pathogenesis of systemic lupus erythematosus (SLE) and their association with disease activity.


METHODS
Gene expressions of T-bet, GATA-3, interferon-gamma (IFN-gamma), and interleukin 4 (IL-4) in peripheral blood mononuclear cells, and plasma concentrations of the Th1/Th2 cytokines IFN-gamma, IL-18, and IL-4, were assayed in 80 patients with SLE and 40 sex and age matched healthy subjects by real-time quantitative polymerase chain reaction and ELISA.


RESULTS
The mRNA levels of T-bet and IFN-gamma and the relative expression levels of T-bet/GATA-3 and IFN-gamma/IL-4 were significantly higher, in contrast to the lower expressions of GATA-3 and IL-4, in SLE patients than controls (all p < 0.05). In all SLE patients, there were significant correlations in mRNA expression of T-bet with IFN-gamma (r = 0.590, p < 0.0001), and of GATA-3 with IL-4 (r = 0.245, p = 0.029). The relative expressions of T-bet/GATA-3 and IFN-gamma/IL-4 correlated with lupus disease activity (r = 0.229, p = 0.042; r = 0.231, p = 0.040, respectively). Plasma IL-18 concentration was increased significantly in all SLE patients (p < 0.05). The elevated plasma Th1/Th2 cytokine ratio IL-18/IL-4 correlated positively with disease activity in all SLE patients (r = 0.250, p = 0.025).


CONCLUSIONS
There is an association between expression of Th1/Th2 transcription factors and cytokines in SLE. The elevated gene expressions of Th1/Th2 transcription factors and cytokines should provide a useful tool for assessing the functional status of T-helper lymphocytes in SLE disease development.
Lit
Lydia Choi-Wan
LC
Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong. lcwlit@cuhk.edu.hk
Wong
Chun-Kwok
CK
Li
Edmund Kwok-Ming
EK
Tam
Lai-Shan
LS
Lam
Christopher Wai-Kei
CW
Lo
Yuk-Ming Dennis
YM
D000328:Adult; D016022:Case-Control Studies; D018450:Disease Progression; D050990:GATA3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D020382:Interleukin-18 / Q000235:genetics / Q000378:metabolism; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism; D018417:Th1 Cells / Q000378:metabolism* / Q000473:pathology; D018418:Th2 Cells / Q000378:metabolism* / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D000098815:T-bet Transcription Factor
D050990:GATA3 Transcription Factor; D020382:Interleukin-18; D012333:RNA, Messenger; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D014157:Transcription Factors; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma