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Elevated Gene Expression of Th1/Th2 Associated Transcription Factors Is Correlated with Disease Activity in Patients with Systemic Lupus Erythematosus
LYDIA CHOI-WAN LIT, CHUN-KWOK WONG, EDMUND KWOK-MING LI, LAI-SHAN TAM, CHRISTOPHER WAI-KEI LAM, and YUK-MING DENNIS LO ABSTRACT. 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-g (IFN-g), and interleukin 4 (IL-4) in peripheral blood mononuclear cells, and plasma concentrations of the Th1/Th2 cytokines IFN-g, 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-g and the relative expression levels of T-bet/GATA-3 and IFN-g/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-g (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-g/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). Conclusion. 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. (First Release Nov 15 2006; J Rheumatol 2007;34:89–96) Key Indexing Terms:
SYSTEMIC LUPUS ERYTHEMATOSUS From the Department of Chemical Pathology and Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong. L.C.W. Lit, MSc, Scientific Officer; C.K. Wong, PhD, Associate Professor; C.W.K. Lam, PhD, Professor; Y.M.D. Lo, DPhil, MD, Associate Dean, Professor, Department of Chemical Pathology; E.K. Li, MD, Professor; L.S. Tam, MD, Medical Officer, Department of Medicine and Therapeutics. Address reprint requests to L.C.W. Lit, Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong. E-mail: lcwlit@cuhk.edu.hk Accepted for publication July 17, 2006. |
