| Abstract Objective:The aim of this study is to probe into the role of transcription factors T-bet, GATA-3 in the pathogenesis of Hench-schonlein purpura in children, and the relationship between CD4+CD25+regulatory T cells, transcription factor FoxP3 and the development of children HSP, then to illustrate molecular mechanisms of Th1/Th2 imbalance of child Hench-schonlein purpura in acute stage at a deeper level, and to clarify pathogenesis of Hench-schonlein purpura from the regulatory T cells and its regulation. So the experiment may provide a new approach and strategy for the treatment of Hench-schonlein purpura especially serious HSP at the molecular level. Methods:1.The expression of T-bet, GATA-3 and FoxP3 mRNA were detected by Real Time PCR using SYBR Green I in 46 patients with HSP in the acute phase.2. In the plasma the expression of cytokine IL-2, IL-4, IL-10 and IFN-y was detected by Luminex and the expression of TGF-β1 was analyzed by ABC-ELISA in 46 patients with HSP in the acute phase.3. The expression of T lymphocyte subsets CD3+, CD3+CD4+, CD3+CD8+, CD4+CD25+ and B lymphocytes CD19+ was detected by flow cytometry on peripheral blood mononuclear cells in 46 patients with HSP in the acute phase.4. The experiment data were analyzed by statistical software SPSS16.0 (student t test). Results:1. The relative level of GATA-3 mRNA in peripheral blood mononuclear cells of patients with HSP (964.3±655.18) was significantly higher than those of the control group (78.09±57.20) (P＜0.01).2. The relative level of T-bet mRNA in peripheral blood mononuclear cells of patients with HSP (53.98±35.79) lower than those of the control group (181.56±96.90) (P<0.01).The relative level of FoxP3 mRNA in peripheral blood mononuclear cells of patients with HSP (32.17±23.04) lower than those of the control group (147.91±99.15) (P<0.01). In HSP patients with renal lesions relative levels of transcription factorsT-bet, GATA-3, FoxP3 mRNA respectively were 54.23±27.64,966.31±594.11,34.13±21.26. In the HSP with without renal lesions relative levels of transcription factors T-bet, GATA-3, FoxP3 mRNA were 49.79±31.25,951.31±632.48,30.21±19.78 respectively, There was no significant difference between the two groups by T-test (P>0.05).3. The expression of plasma cytokines IL-2, IL-10, IFN-y in HSP was 16.54±7.38 pg/ml,59.30±40.31 pg/ml,11.31±8.02 pg/ml. The expression of control group was 35.73±22.66 pg/ml,135.42±93.15 pg/ml,30.67±21.29 pg/ml respectively. The expression of HSP was higher than those of the control group, the difference was statistically significant (P<0.01) between HSP group and control group. The expression of plasma cytokines IL-4 and TGF-β1 in HSP (74.66±26.15 pg/ml,488.02±193.08 pg/ml) was higher than those of the control group (51.81±27.76 pg/ml,273.03±185.79 pg/ml) significantly (P＜0.01). In HSP patients with renal lesions expression of cytokine IL-2, IL-10, IFN-γ, IL-4, TGF-β1 was 17.28±6.54 pg/ml,57.65±41.65 pg/ml,9.85±8.17 pg/ml, 76.72±25.44 pg/ml,492.77±191.46 pg/ml respectively. In HSP patients without renal lesions expression of cytokine IL-2, IL-10, IFN-γ, IL-4, TGF-β1 was 16.98±7.21 pg/ml,62.13±44.32 pg/ml,13.02±7.97 pg/ml,68.95±23.51pg/ml, 477.96±189.32 pg/ml respectively, no significant difference between the two groups(P＞0.05).4. The results of CD3+, CD3+CD4+, CD3+CD8+, CD4+/CD8+ CD4+CD25+ on peripheral blood mononuclear cells of HSP were 62.7±8.52%, 30.61±6.93%,31.42±6.65%,1.02±0.37%,5.34±2.51% respectively. The results of control group were 65.04±6.50%,35.98±4.19%,30.72±16.5%, 1.18±0.35%,7.85±1.97% respectively. The expression of HSP group was higher than those of control group. The difference was significant (P<0.01), but the increase in CD8+ no significant difference between the two groups (P> 0.05). The expression of CD19+ in HSP was 23.16±7.37%. The expression of CD19+ in the control group was 18.91±3.53%. There was significant difference between the groups (P<0.01). In HSP patients with renal lesions results of T cell subsets CD3+, CD3+CD4+, CD3+CD8+, CD4+/CD8+, CD4+CD25+and B lyphonecyte CD19+ were 64.83±8.25%,33.12±7.01%,31.71±7.03%, 1.10±0.36%,4.28±1.92%,20.81±8.40%respectively. In HSP patients without renal lesions results of T cell subsets and CD19+ were 61.22±8.11%, 30.75±4.43%,29.44±9.22%,1.15±0.41%,5.85±2.47%,25.58±5.84%, 1.97±1.31% respectively. There was no significant difference between the two groups (P>0.05). Conclusion:1.There is functional disorder of T lymphocyte subsets and activation of B lymphocyte proliferation at acute phase of Henoch-Schonlein purpura in children.2 Thl/Th2 imbalanceexists in acute phase of children HSP, especially predominant activation of Th2, which has a relationship with the abnormal expression of transcription factor T-bet mRNA, Gata-3 mRNA. This study clarifies the imbalance of Th1/Th2 from one of molecular mechanisms.3. In acute phase of children HSP, the expression of CD4+CD25+regulatory T cells is reduced, and its special transcription factor FoxP3 mRNA is decreased, which indicated that insufficient immunosuppressive effects resulting from the reduction of regulatory T cells may be one important reason the immune imbalance of HSP acute phase. So the results provide experimental evidence for illustrating the pathogenesis of Hench-schonlein purpura from molecular mechanism of regulatory T cells and its regulation, and then provide a new thinking and new strategies for the treatment of HSP especially serious HSP at molecular levels. |
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