Evaluation Of Complement Factor H And Complement Factor H Related Proteins In Idiopathic Membranous Nephropathy

Objective:This study aimed to investigate the levels of FH,FHR1,and C5a in the serum of IMN patients,to explore the differences in levels between IMN patients and healthy controls,and to discuss the role of complement alternative pathway regulators in the pathogenesis of IMN.Besides,this study aimed to detect associations between meaningful complement markers and other kidney parameters.Methods:98 patients with IMN from Shengjing Hospital of China Medical University were diagnosed with IMN by renal biopsy.They were diagnosed with IMN for the first time and without treatment.Twenty-three healthy individuals with matching age and gender were recruited from Shengjing Hospital,China Medical University.Serum concentrations of FH,FHR1,and C5a were determined by enzyme-linked immunosorbent assay.The IMN patients were divided into two groups with and without the nephrotic syndrome.The differences in FH,FHR1,and C5a concentrations between the IMN group and the healthy control group were analyzed,as well as the differences in three biomarkers of complement between the group with and without the nephrotic syndrome.Their linear relationship with kidney parameters and their correlation with complement biomarkers were also evaluated.Results:1.The concentration of FH,FHR1,and C5a in IMN group were0.52（0.40-0.66）（μg/ml）/(ml·min^-1·1.73m^-2),2.53（1.73-3.49）（μg/ml）/(ml·min^-1·1.73m^-2)and 2.42（1.23-6.36）（ng/ml）/(ml·min^-1·1.73m^-2);The concentration of FH,FHR1,and C5a in healthy control group were 0.57（0.39-0.69）（μg/ml）/(ml·min^-1·1.73m^-2),1.07（0.87-1.64）（μg/ml）/(ml·min^-1·1.73m^-2)and0.67（0.56-0.96）（ng/ml）/(ml·min^-1·1.73m^-2).Compared to the healthy control group,the level of serum FHR1 and C5a were significantly higher in the IMN group（P<0.001）.The level of serum FH showed no statistical differences.2.The concentration of FH,FHR1 and C5a in IMN group with nephrotic syndrome were 0.50（0.39-0.63）（μg/ml）/(ml·min^-1·1.73m^-2),2.83（2.01-3.70）（μg/ml）/(ml·min^-1·1.73m^-2)and4.61（1.32-6.59）（ng/ml）/(ml·min^-1·1.73m^-2)respectively.The concentration of these three biomarkers in IMN group without nephrotic syndrome were 0.55（0.42-0.73）（μg/ml）/(ml·min^-1·1.73m^-2),1.73（1.17-2.72）（μg/ml）/(ml·min^-1·1.73m^-2)and 2.14（1.14-5.03）（ng/ml）/(ml·min^-1·1.73m^-2).Compared to the IMN group without the nephrotic syndrome,the concentration of FHR1 was significantly higher in the IMN group with nephrotic syndrome（P<0.001）.The level of serum FH and C5a showed no statistical differences between the IMN group with or without nephrotic syndrome（P>0.05）.3.The level of serum FHR1 and C5a showed a significantly positive correlation with other renal parameters in the IMN group.4.The concentration of serum FHR1 showed a significantly positive correlation with C5a in the IMN group.Conclusion:Serum levels of FHR1 and C5a are associated with disease status in patients with idiopathic membranous nephropathy.The serum levels of FHR1,a key regulator of the complement alternative pathway,and serum levels of C5a showed significant differences between IMN patients and healthy controls.Activation of the complement alternative pathway may be involved in the pathogenesis of idiopathic membranous nephropathy.