A Study On The Clinical And Pathological Features Of Membranous Nephropathy With Secondary Factors And The Expression Of PLA2R And Subclasses Of IgG

Objectives A retrospective study analyzed the clinical and pathological characteristics of membranous nephropathywith secondary factors(SMN),as well as the expression of PLA2R&IgG subclasses in renal tissue and serum anti-PLA2R antibody in those patients,in order to improve the awareness of the features of SMN and to be helpful to the differential diagnosis of SMN.Methods 203 SMN patients confirmed by renal biopsies in Rui Jin Hospital Shanghai Jiao Tong University School of Medicine from January 2002 to December 2014 were reviewed and analyzed their clinical,pathological datas and 475 patients diagnosed as primary membranous nephropathy(PMN)were collected as controls.The SMN patients were devided into 3 subgroups(SLE,infection of hepatitis B virus and malignancy)according to the different etiology and analyzed their clinical and pathological characteristics of each subgroups.IgG subclasses,PLA2R deposition in glomeruli and serum PLA2R antiboby were detected by immunofluorescence to compare the differences of their expression and the relationship of PLA2R between renal biopsy and serum.Results The everage age of enrolled patients was 45.9±17.1,which was younger than PMN.Male to femal ratio was 1:1.03.The most common secondary causes was autoimmune diseases(44.3%,68/203),among which,type V lupus(MLN)was commonest disease(33.5%,68/203).The second place of cause was infection(39.4%,80/203),the majority cause of which is HBV infection(35.5%,72/203),followed by malignancy(9.9%,20/203).15%-23.g%of total MN patients existed secondary factors.Compared with PMN,the incidence of nephrotic syndrome(NS),hypertriglyceridemia,hypercholesterolemia and the level of systolic blood pressure,serum C3 were lower in SMN.While the incidence of renal dysfunction and the level of serum IgG and IgA in SMN were higher than PMN.The tubular atrophy,interstitial fibrosis and inflammatory cell infiltration were more severe and the glomerular deposit of IgA,IgM,C4 and C1q were greater in study group than in PMN group,while vascular damage and C3 deposit were less.Compared with Ⅴ+Ⅲand Ⅴ+Ⅳ type LN,MLN had lower incidence and severity of NS,microscopic hematuria,renal dysfunction,hypocomplementemia and increased serum anti-dsDNA.It showed lower expression of C3,C4,C1q and mesangial&subendothelial electron dense deposits in MLN than in MLN with proliferative LN.In MN patients with HBV infection,the incidence of NS and level of serum C3,C4 were lower than PMN patients,while the serum creatine was higher in HBV-MN group.MN with active HBV infection tend to have greater incidence of segmental sclerosis,C4,C1q expression,mesangial and subendothelial electron dense deposits.The age of MN with malignancy tend to be older than PMN and other SMN groups.Deposition of anti-PLA2R antibody was observed in 41.8%of renal samples obtained from total SMN and 64.3%of HBV-MN,57.1%of MN with malignancy.All samples from MLN showed no staining of anti-PLA2R.In renal PLA2R positive sample group,the subclasses of deposited IgG was predominantly IgG4 and IgG1 and the highest immunofluorescence intensity was observed in IgG4.However,the positive rate and the staining intensity of IgG1 were both highest in renal PLA2R negative sample group.The positive rate of anti PLA2R in serum was 60.0%in patients with SMN and 71.4%in HBV-MN,60.0%in MN with malignancy.IgG1 was expressed predominantly in MLN,while IgG1,IgG2 and IgG3 were codeposited in MLN combined with proliferative LN.The subclasses of deposited IgG was predominantly IgG1 and IgG4 in MN with HBV infection and malignancy.The most common and highest staining intensity IgG subclasses in PMN was IgG4.Conclusion The age of patients with SMN is younger than those with PMN.The HBV infection and LN are the most common etiology for SMN.The incidence of NS and serum complement C3 level in SMN is lower than that in PMN.More SMN patients suffer from renal impairment.The renal tubulointerstitial lesions are more severe in SMN than in PMN.Immunoglobulins and complements deposition in glomeruli in SMN are more common than that in PMN.Compared to MLN combined with proliferative LN,pure MLN had lower serverity of clinical and pathological features.The expression of PLA2R and IgG1-4 are different in MN with different secondary factors.The detection of PLA2R in serum and renal tissue is helpful for the differential diagnosis of MLN,MN with other secondary factors and PMN.