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Objective:To evaluate the curative efficacy of tacrolimus (FK506)combined with corticosteroids in the treatment of idiopathic membranous nephropathy (IMN ), and to analyze the response of anti-M-type phospholipase A2 receptor (PLA2R)antibody to the treatment.Methods:Sixty-one adult IMN patients were divided into FK506 group (FK506 combined with corticosteroids,n = 24)and CTX group (cyclophosphomide combined with corticosteroids,n=37)according to their willing to the acceptance of different immunosuppressives. The remission rates of the patients at 4,8,12 and 24 weeks after treatment in two groups were analyzed.The ELISA method was used for the detection of serum anti-PLA2R antibodies of the patients before and after treatment.The antibody level changes were observed and the difference of remission rates was compared between the antibody positive patients and the negative patients in FK506 group.Results:The total remission rates of the patients in FK506 and CTX groups 24 weeks after treatment were 91.7% and 64.9% respectively and the total remission rate of the patients in FK506 group was significantly higher than that in CTX group (P 0.05).The total remission rates of the antibody positive patients and negative patients at baseline in FK506 group 24 weeks after treatment were 88.9% and 100.0%,respectively;there was no significant difference (P > 0.05).Except the characteristic side effects of corticosteroids,the patients in FK506 group presented no hyperglycemia,tubulointerstitial damage,hepatic lesion or neurotoxicity. But the patients in CTX group showed mild hepatic lesion or gastrointestinal symptoms.Conclusion:The remission rate of FK506 combined with corticosteroids is higher than that of CTX combined with corticosteroids in the treatment of IMN patients.FK506 treatment has relatively rapid effect and less side effects as well.The negative conversion of serum anti-PLA2R antibody follows the remission after treatment;however,the negative conversion rate has no significant difference between FK506 group and CTX group.The remission rate of IMN patients treated with FK56 combined with hormone has no relationship with the baseline anti-PLA2R antibody.
ABSTRACT
Objective To investigate the correlation of M-type phospholipase A2 receptor (PLA2R) genetic polymorphism in two single nucleotide polymorphisms (SNPs) with idiopathic membranous nephropathy (IMN) of Chinese Han population in Northeast China.Methods A total of 327 individuals were enrolled in the study including 95 adult patients with biopsy-proved IMN (IMN group) followed up for (25.4±11.6) months and 232 healthy people identified by healthy examination in China-Japan Union Hospital of Jilin University (HC group).Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to detect the genotype and allele frequency of rs35771982 and rs3828323 site in PLA2R gene.The x2 test was performed to compare the distribution difference of allelic frequency and genotype frequency of the two sites in PLA2R gene between two groups.Unconditional Logistic regression analysis was used to determine the risk factor of IMN.Results IMN and HC group were matched in male predominance and body mass index (BMI).Patients with IMN were older than the healthy controls and had higher Scr,serum total cholesterol (TC),24-hour urine protein level and lower serum albumin (Alb) level,lower estimated glomerular filtration rate (eGFR) than the healthy controls (all P ＜ 0.01).The CC genotype frequency and the C allele frequency at SNP rs35771982 site of PLA2R gene in IMN group were significantly higher than those in HC group (x2=13.658,P=0.001;x2=15.315,P=9.10× 10-5),whereas there was no distribution difference of genotype and allele frequency at rs3828323 site between two groups (x2=2.844,P =0.241; x2 =2.959,P=0.085).The CC genotype at rs35771982 site in patients with IMN was not related to,age,gender,BMI,blood pressure and several laboratory indexes such as Alb,TC,Scr,eGFR and 24-hour urine protein level (all P ＞ 0.05).Unconditional Logistic regression analysis revealed that the genotype at rs35771982,age,TC,Scr and eGFR were correlated with IMN occurrence.The CC genotype at rs35771982 was the risk factor of IMN (OR =4.408,95％CI 1.488-13.058).Conclusions The CC genotype and C allele at rs35771982 site in PLA2R may be associated with the susceptibility to IMN,whereas the correlation between gene polymorphism at rs3828323 site and IMN is not demonstrated.The CC genotype at rs35771982 is the independent risk factor of IMN in Chinese Han population in Northeast China.
ABSTRACT
Objective To investigate the correlation of serum anti-M-type phospholipase A2 receptor (PLA2R) antibody with laboratory parameters of idiopathic membranous nephropathy (IMN) in adult patients with membranous nephropathy (MN),and to explore the role of anti-PLA2R antibody in the pathogenesis of IMN. Methods Forty-six adult patients with biopsy-proved glomerular diseases were involved in this study,including 20 cases with IMN,7 cases with IgA nephropathy (IgAN),6 cases with hepatitis B-associated membranous nephropathy (HBV-MN),6 cases with minimal change nephropathy (MCN),4 cases with focal segmental glomerulosclerosis (FSGS) and 3 cases with class Ⅴ lupus nephritis.Total RNA was extracted from human glomeruli and was reversely transcribed to the first-strand cDNA.The full-length human M-type PLA2R was amplified by PCR and the 605 bp product was subcloned into eukaryotic expression vector containing CMV promoter.The recombinant human M-type PLA2R plasmid vector was transiently transfected into human embryonic kidney (HEK) 239T cell line using the FuGene6 transfection reagent.Western blotting was used to detect serum anti-PLA2R antibodies.Correlations of antiPLA2R antibody level with laboratory parameters,including serum albumin,total cholesterol,Scr and 24-hour urine protein,of IMN patients were evaluated. Results Among 20 cases with IMN,15 cases showed positive anti-PLA2R antibodies (positive rate 75％).Of 7 cases with IgAN and 6 cases with HBV-MN,only 1 case showed positive anti-PLA2R antibody respectively (positive rate 14.29％ and 16.67％ respectively).Anti-PLA2R antibody was negative in other patients.The positive rate of anti-PLA2R antibody in IMN patients was significantly higher than that in patients with secondary MN and other types of glomerlonephritis (all P＜0.01).Furthermore,anti-PLA2R antibody level was positively correlated with 24-hour urine protein(r=0.803,P＜0.01) and negatively correlated with serum albumin in IMN patients (r=-0.816,P＜0.01). Conclusions The high positive ratio of anti-PLA2R antibody may indicate that it is the specific autoantibody in IMN.AntiPLA2R antibody is correlated with IMN disease severity,which indicates that it may be the pathogenic autoantibody in IMN.