Role Of Th1/Th2Polarization And IgA Anti-cardiolipin Antibodies In Serum In Pathologic Mechanism Of Henoch-schonlein Purpura In Children

Objective:Henoch-Schonlein purpura (HSP) is the most commontype of systemic vasculitis in childhood. It is characterized by a triad ofpalpable purpura (without thrombocytopenia),abdominal pain, andarthritis. Renal involvement is the leading cause of progressiveglomerulonephritis in childhood. Infections, or other environmental factormay trigger antibody and immune complex formation. Flow cytometrie(FCM) and Enzyme linked immunosorbent assay (ELISA) weremeasured IFN-γ and IL-4both in Intracellular staining of lymphocytesand in serum, to explain the roles of Th1/Th2paradigm at the acute stageof childhood HSP. Meanwhile,Immunoturbidmetry and ELISA wereused to detect to the level of immunoglobulin A(IgA)and IgA isotype ofanti-cardiolipin antibodies (aCL) in serum, to explain the roles of at theacute stage of childhood HSP. By analysis the relationship betweenTh1/Th2paradigm and the level of immunoglobulin A have beenproposed as mechanisms underlying pathogenesis of HSP. IgA aCLserum levels in group of renal involvement were significantly elevated inpatients compared with the group without renal involvement. To explorethe correlations between IgA aCL serum levels and the percentage of Th2or IgA aCL serum levels and Th2response related cytokines in childrenwith HSP. Giving anticoagulant therapy in early stage and regulatingTh1/Th2balance may be helpful to prevent the occurrence ofHenoch-Schonlein Nephritis.Methods: A total of36previously healthy children with acute HSPwere enrolled in this study. There were20males and16females with anage range of3-12years. The diagnosis of HSP was made according to the International Consensus Conference2006criteria during the period fromJanuary2011to February2012at the third Hospital of Hebei MedicalUniversity.None of the patients had been given corticosteroids,immunosuppressants, at the time of serum sampling. Furthermore, nopatient demonstrated any evidence of autoimmune diseases, or vasculitis.Informed consent and Institutional approval were obtained for the study.According to renal involvement, the group was divide into group A1withno renal involvement and group A2with renal involvement. Twentyhealthy children with comparable sex and age distributions were recruitedas normal controls as group B. FCM analysis was performed to detect thepercentage of CD3+CD8-INF-γ+IL-4-(Th1), CD3+CD8-INF-γ-IL-4+(Th2). ELISAwas used to detect the levels of INF-γ,IL-4,IgAaCL inserum.Results:1. The data showed that elevation of leucocytes, neutrophil percentage,platelet counts and CRP were significantly higher at the acute stage ofHSP than the healthy controls. The percentage of Th1cell and the levelsof its related cytokines IFN-γ in serum decreased, and the percentage ofTh2cell and the levels of their related cytokine IL-4increased ascompared to the healthy controls.2.The percentage of Th1and Th2cells and the levels of their relatedcytokines IFN-γ and IL-4from group A1was no different compare withthat in group A2. And the serum IgA antibodies level of group A1was nodifferent compare with group A2.By contrast, the serum IgA aCL level ofgroup A2was increased significantly than group A1.3．The serum IgA antibodies levels was positively correlation with thepercentage of Th2cells during the acute stage of HSP.4. The serum IgA aCL level was positively correlation with the serumIgA antibodies levels during the acute stage of HSP.5. The serum IgA aCL levels was positively correlation with thepercentage of Th2cell during the acute stage of HSP. 6. There was no different in the levels of serum IgA aCL and IL-4duringthe acute stage of HSP.Conclusions:1The elevation of leucocytes, neutrophil percentage, platelet counts andCRP reflected the nature of acute inflammatory process. That reflectsinfections possible one of the reasons at the onset of HSP.2The decrease of the percentage of Th1cells in PBMC and its relatedcytokines IFN-γ in serum,and the increase of the percentage of Th2cellsand its related cytokines IL-4in serum. Besides Th1/Th2ratio depends onIFN-γ/IL-4ratio variety. That reflects Th1/Th2paradigm play animportant role in immunopathogenesis of HSP.3The increase of the serum IgA antibodies was positive correlation withthe percentage of Th2cells.Th2cells secrete Th2cytokines recruit B cellsand drive a B cell class switch leading to the production of IgA.4The acute of HSP was existence of hypercoagulable state,because ofthe increased of serum IgA aCL. And these hypercoagulable state was theresult in kidney damage.5The serum IgA aCL level was positively correlation with the serum IgAantibodies levels suggested IgA aCL is an important component ofcirculating IgA antibodies.