Effects Of TFH On The Pathogenesis Of Henoch-sch?nlein Purpura Through CD40/CD40L Axis

Objective: To explore the level of CD19+B cells and the imbalance of immunoglobulin expressed by CD19+B cells in Henoch-Sch?nlein purpura(HSP)/Henoch-Sch?nlein purpura nephritis(HSPN)and to investigate the effect of T follicular helper(TFH)on the development of HSP/HSPN in children through CD40/CD40 L axis.Methods: Total of 44 cases of HSP/HSPN in the acute period were selected and divided into 3 groups as follows: 22 HSP children without renal involvement(Group A);11 HSPN children with only microhematuria(Group B);11 HSPN children with both microhematuria and proteinuria(Group C).11 healthy children were selected as normal control group(Control).The percentages of CD19+B cells,CD19+B subsets(memory: CD19+CD27+B cells,active: CD19+CD86+B cells,plasma cells: CD19+CD138+B cells)and the expression of different Ig classes(IgA,IgE,IgG,Ig M,IgD)by CD19+B cells and CD19+CD38+B cells,CD40 by CD19+B cells and CD19+B cell subsets,CD40 ligand(CD40L)by TFH and TFH subsets(TFH1,TFH2,TFH17)were detected with flow cytometry.The correlations between CD19+IgA+B cells,CD19+CD38+IgA+B cells and CD40L+TFH cells,CD40L+TFH2 cells,CD40L+TFH17 cells were analyzed.Results: Compared with the Control group,the percentages of CD19+CD86+B cells and CD19+CD138+B cells in Group C were significantly increased(P<0.05),whereas,above indexes in Groups A,B were increased,although the differences were not significant(P>0.05).The percentages of CD19+B cells and CD19+CD27+B cells and the expression of IgG,IgM,IgD by CD19+B cells and CD19+CD38+B cells,the expression of CD40 by CD19+ B cells and CD19+B subsets in Groups A,B,C showed no significant difference in Group A versus the Control group(P>0.05).Moreover,the expression of IgA,IgE by CD19+B cells and CD19+CD38+B cells were increased in Groups A,B,C compared with the Control group(P<0.05).Compared with the Control group,the percentages of CD40L+TFH cells,CD40L+TFH1 cells,CD40L+TFH2 cells and CD40L+TFH17 cells in Group C were significantly increased(P<0.05),whereas,above indexes in Groups A,B were increased,although the differences were not significant(P>0.05).Moreover,CD40L+TFH cells showed positive correlated with CD19+IgA+B cells(R=0.3489,P<0.05)and CD19+CD38+IgA+B cells(R=0.3196,P<0.05).The correlations between CD40L+TFH1 cells and CD19+IgA+B cells,CD19+CD38+IgA+B cells were not significant(P>0.05).CD40L+TFH2 cells showed positive correlated with CD19+IgA+B cells(R=0.3365,P<0.05)and CD19+CD38+IgA+B cells(R=0.314,P<0.05).CD40L+TFH17 cells showed positive correlated with CD19+IgA+B cells(R=0.3108,P<0.05)and CD19+CD38+IgA+B cells(R=0.3175,P<0.05).Conclusion: In conclusion,active B cells(CD19+CD86+B cells)and plasma cells(CD19+CD138+ cells)were increased significantly,which may be a sensitive indicator of early renal damage in children with HSP,especially the occurrence of proteinuria.TFH mediated abnormal CD40/CD40 L signaling pathway may play an important role in the development of HSP and the clinical severity of renal involvement.