The Role Of Factor H And Its Related Proteins In The Complement Alternative Pathway Of Henoch-Schonlein Purpura

Henoch-Scholein purpura(HSP)is a kind of systemic small vasculitis with IgA1 immune complex deposition.The etiology and pathogenesis are still unclear.The complement system plays an important role in the pathogenesis of Henoch-Scholein purpura,which can form a membrane attack complex(MAC)to destroy the target cell membrane,and enhance the accumulation of neutrophils to mediate vascular endothelial cell injury.Studies have shown that complement mainly activates through the complement alternative pathway,but currently the activation and regulation of the complement alternative pathway of HSP has not been studied.Factor H(FH)is a main inhibitor of complement alternative pathway activation,while factor H-related protein(FHR)can indirectly activate complement by inhibiting the function of factor H.The balance between action of factor H and FHR determines the extent of complement activation.The role of galactose-deficient IgA1(Gd-IgAl)in HSP has been widely discussed,and in vitro experiments have shown that complexes containing Gd-IgA1 can activate the complement alternative pathway.Thus we can make a speculation,Gd-IgA1 may activate the alternative pathway of complement in HSP,and factor H and its related proteins regulate the procedure.Objective:To detect the levels of factor H,FHR1,Gd-IgA1 and complement Bb in peripheral blood of patients with HSP;To analyze the role of factor H and its related proteins in complement system in HSP;To investigate whether the Gd-IgA complex can activate complement by the alternative pathway.Method:1.Research objectA total of 33 patients in acute stage and 7 patients in convalescent stage after treatment were enrolled in the outpatient or ward of the Second Hospital of Hebei Medical University from December 2017 to June 2018.According to clinical manifestations and laboratory tests,33 patients in acute phase were divided into 4 groups: skin type group 21 cases;joint group 4 cases;abdominal type group 3 cases;kidney type group 5 cases.Normal control group: 36 healthy volunteers.2.Research methodsThe levels of serum FH,FHR1,Gd-IgAl Bb in each group were detected by ELISA.3.Statistical analysisData were analyzed by statistical software SPSS22.0,statistical difference was considered if P<0.05.If the data were normality and variance,One-way ANOVA was used for comparison between groups.The two-two comparison between groups was tested by LSD method.If not,the Kruskal-Wallis H test in non-parametric test was used.The Spearman method is used for correlation testing.Results:1.FHR1 and FH levels in patients with acute HSP were higher than those in recovery patients and healthy controls(P<0.05).There was no significant difference between the recovery patients and healthy controls(P>0.05).Bb and Gd-IgAl levels in patients with acute and recovery HSP were higher than those in healthy controls(P<0.05),but there was no significant difference between acute and recovery patients(P>0.05).2.The level of FHR1 in all subgroups of acute HSP was higher than the control,and the renal subgroup was the highest.3.Spearman correlation analysis: Serum Gd-IgAl and FHR1 were positively correlated with Bb level in HSP patients.Conclusion:1.Increased serum Bb levels in patients with acute HSP suggestive of activation of the complement alternative pathway in HSP patients.Gd-IgAl and FHR1 was positively correlated with Bb level,suggesting that Gd-IgA1 can act as an activator of the complement alternative pathway and FHR1 protein may enhance the activation of the complement alternative pathway.2.Compared with the other three groups of HSP patients,the elevation of FHR1 was more obvious in the renal purpura group,suggesting that FHR1 levels are closely related to renal injury.3.Serum FHR1 and FH levels were elevated in patients with acute HSP,but were normal in convalescent stage.They may be used as indicators of disease activity.4.The complement activation by increased Gd-IgAl and FHR1 may be important keys in the pathogenesis of HSP.5.Correcting the abnormality level of serum Gd-IgA1 and FHR1 in HSP patients may help the recovery of HSP patients.Complement inhibitor treatment may be beneficial for HSP patients.