Investigation Of The Immunopathogenesis Of Henoch-Schonlein Purpura

Objective:To investigate the role of signal transduction of TLRs and the changes of CD4+ T cell subset in the Henoch-Schonlcin purpura (HSP). Methods:1:Rcvcrsc-transcription PCR (RT-PCR) and real-time PCR were used to evaluate the levels of TLRs (1-10) MyD88, TRAF6, TRIF, IFN-a, IFN-β, IL-6, IL-1β, TNF-a, IP-10, RENTES, iNOS, Blys/April mRNA expression in peripheral blood mononuclear cells and their expression levels were compared using t test, while concentrations of plasma cytokines such as Blys,IFN-α,IFN-β,IL-6,IL-1βTNF-a were measured by enzyme-linked immunosorbent assay (ELISA).2:Real-time PCR was used to evaluate the expression levels of transcriptional factors and cytokines mRNA from CD4+T cells. Proportions of Thl, Th2, Th17 and Treg cells in peripheral blood were detected by flow cytometric analysis. Plasma cytokine concentrations were measured by ELISA. Results:1,The role of activation of toll-like receptors in immunological pathogenesis of Henoch-Schonlein purpura:(1) Compared with control group, the expression levels of TLR1, TLR2, TLR6, TLR5, TLR3, TLR7, TLR9 mRNA were up-regulated significantly (p<0.05), while no difference of TLR4 was detected (p>0.05).(2)Transcription levels of MyD88(2.47±1.06) vs (0.73±0.22),TRAF6 (2.54±0.72)×10-3vs (0.70±0.20)×10-3,TRIF (3.18±0.86)×10-3 vs (0.93±0.35)×10-3 were significantly up-regulated in acute phase of HSP (p<0.05).(3) The levels of IFN-a and IFN-(3 protein and mRNA were remarkable increased (p<0.05).(4) Expressions of cytokine/chemotactic factor such as IL-6,IL-1β,IP-10,RENTES,iNOS were higher than those of control group (p<0.05), while TNF-a did not change in children with HSP (p>0.05).(5) It was detected that expressions of Blys/April were higher than those of the control group (p<0.05).2,Investigation of the change of CD4+T cell subset in children with Henoch-Schonlein purpura:The proportions of Th2 and Th17 cells in peripheral blood from children with HSP were significantly increased than those of health controls (P<0.05), while there were no significant differences between HSP and healthy controls regarding the proportions of Treg cells and Th1 cells (P>0.05). Transcriptional factors and cytokines of Th2 and Th17 cells mRNA levels were significantly up-regulated (p<0.05), while the differences were not significant as to those of Thl and Treg cells (p>0.05). Concentrations of IL-17A.IL-4, IL-6 were higher than those of the control group (p<0.05), while no difference of IFN-γ,IL-12,TGF-βwere detected (p>0.05).Conclusion:1,Expressions of TLR1, TLR2, TLR6,TLR5, TLR3, TLR7, TLR9, MyD88, TRAF6, and TRIF were up-regulated during acute phrase in HSP, suggesting that aberrant activation of TLRs triggered by microbes might be one of the initiating factors of immune aberrance in HSP. Over expression of cytokine/chemotactic factor or Blys/April owning to the aberrant activation of TLRs, might be correlated with immunological pathogenesis of HSP.2,There is an imbalance of CD4+T cell subset in children with HSP, high expression of Th2 and Thl7 cells might be closely correlated with aberrant creation of antibody and development of vessel vasculitis. The changes of cytokine milieu in peripheral blood may play an important role in the derangement of CD4+T cell subset.