| Background: Systemic Lupus Erythematosus(SLE)is a chronic autoimmune disease and many factors are involved in the occurrence and development of gender differences in SLE.CFH plays a very important role in the pathogenesis of lupus nephritis,but its specific mechanism has not been fully clarified.Recently,the presence of tertiary lymphoid tissue(TLT)in the renal tissue of LN has been discovered as a kidney-specific immune organ.The relationship between CFH and TLT in renal tissue has not been reported.In this study,the differences in plasma CFH levels between male and female MRL/ lpr mice,male and female healthy controls,and lupus nephritis patients were observed,and the relationship between CFH levels in MRL/ lpr mice and the formation of serum CXCL13,BAFF and renal TLT was studied.Methods:(1)Male and female adult MRL/lpr mice were used as research subjects,and blood urea nitrogen,creatinine,anti-ds DNA antibody,urinary protein and urinary albumin at different weeks of age,and the plasma complement components were analyzed.And the correlation between blood complement components and renal damage indexes were analysed.The difference of blood complement composition between male and female healthy subjects and patients with LN was detected and analyzed.(2)Adult female MRL/lpr mice were divided into control group,CFH group,baricitinib group(JAK inhibitor),the CFH + baricitinib group,compared with male MRL/lpr mice.And urinary protein,urinary albumin,blood complement,anti ds DNA antibodies were detected.CXCL13 and BAFF in serum and kidney were detected,too.At the same time,the morphology,cell number and size of TLT were calculated.To evaluate the effect of CFH on TLT in renal tissue.Results:(1)At 8,14 weeks of age,the levels of complement C5b-9,C3 a,C5a and C4 d in female MRL/ lpr mice were significantly higher than those in male mice,while the levels of CFB and CFH were significantly lower than those in male mice.(2)The blood C3 and CFH levels of healthy female subjects were significantly lower than those of healthy male subjects.The levels of C3,CFH and CFB in patients with lupus nephritis were significantly lower than those in healthy subjects,the differences were statistically significant.(3)At 8 weeks of age,the levels of CXCL13 and BAFF in blood and renal homogenates of female were significantly higher than those of male mice.Correlation analysis showed that CXCL13 and BAFF levels in blood and kidney homogenates were significantly negatively correlated with changes in complement C3,CFB and CFH levels,and positively correlated with changes in complement C5b-9,C3 a,C5a and C4 d levels.(4)Compared to control groups,urinary protein,urinary albumin,urea and creatinine,kidney damage rating were low,and kidney Ig G /C3 staining intensity was lighter,apoptotic cells in kidney cortex was less,but there was no statistically significant difference between the three groups.(3)Compared with baseline and male mice of the same age,the number of TLT in the renal cortex of female control mice was significantly increased,in which activated T cells(Lat)and B cells(CD19)were significantly increased,mainly located around blood vessels and glomeruli.These changes were significantly reduced in CFH group,baritinib group,and CFH+ baritinib group.Conclusion: 1.The blood CFH level of female MRL/lpr mice was lower than that of male in early life.The deterioration of renal function after the activation of the complement system was closely related with CFH.The gender difference was also existed in healthy controls.This suggested CFH may be the important mechanism of the women was susceptible to SLE and LN.2.The formation of TLT in renal tissue of female MRL/ lpr mice was more obvious than that of male mice.Early exogenous CFH supplementation can alleviate these lesions,which is comparable to the effect of JAK inhibitor,suggesting that intervention of TLT formation in renal tissue by early CFH supplementation may improve the prognosis of lupus nephritis. |
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