The Relationship Between The Activity Of Platelet-Activating Factor-Acetylhydrolase (PAF-AH) And Primary Nephritic Syndrome

Primary nephritic syndrome(PNS)is one of the most common renal diseases in childhood.It's clinical features include the intensive proteinuria, hypoalbuminemia,edema and hypercholesterolemia.Usually PNS is classified into two main types:simple type nephritic syndrome(STNS)and nephritic type nephritic syndrome(NTNS).STNS is more common in children,and are well treated with Glucocorticoid therapy differ obviously.However,NTNS is partly responding to and / or resistant to treatment.Right now,Glucocorticoid is still the most commonly used drug in the clinical practice.But the outcomes of the therapy vary.According to their response to steroid application,the patients can be classified into 3 groups as follow:steroid-sensitive group(SSNS)and steroid resistant group(SRNS)as well as steroid-dependent group(SDNS).The relapse rate is very high in children with PNS,which is highly related to the environmental and/or genetic factors.The mechanism of PNS has not completely understood.But it is clear that the cellular immune disturbances are certainly involved and play an important role in the progress of the disease.Many inflammatory mediators,such as IL, TNF are believed to increase the loss of proteins from the glomerular basement membrane.Platelet-activating factor(PAF)may be involved in the pathogenesis of PNS.PAF is degraded into a deactivated form by platelet activating factor acetylhydrolase(PAF-AH)in physical circumstance.The deficiency of PAF-AH is an autosomal recessive genetic disorder, which is associated with many diseases.Objective:(1)To investigate the activity of platelet activating factor acetylhydrolase (PAF-AH)in the children with primary nephritic syndrome.(2)To evaluate the possibe of point mutation of PAF-AH gene in PNS.(3)To investigate whether PAF-AH genotypes are involved in the activity of PAF-AH in children with PNS.(4)To clarify the varieties the relationship between of PAF-AH and different pathological types of PNS.Methods:(1)The plasma PAF-AH activity was determined in 60 healthy children and 94 primary nephritic syndrome children by spectrophotometer assay:simple PNS (n=45)vs.nephritic PNS(n=49).After having received the standard therapy, according to their response to steroid application,the patients could be classified into 3 subgroups as follow:steroid-sensitive group(SSNS,N=37)and steroid resistant group(SRNS,N=26)as well as steroid-dependent group(SDNS, N=31),respectively.(2)The point mutation of PAF-AH gene(G994T)was identified by polymerase chain reaction(PCR)in 94 cases of PNS and 239 healthy children.(3)The activity of plasma PAF-AH was measured in 60 healthy children and 94 PNS children with different genotypes.(4)According to the pathological diagnosis,which was confirmed by renal biopsy,34 PNS children also were be classified into 4 groups:mesangial proliferative glomerulonephritis(MsPGN,N=23),Focal segmental glomerulosclerosis(FSGS,N=5),minimal change nephritic(MCNS,N=3),and other pathological types(N=5).The activity level of PAF-AH were assayed in 60 healthy children and 34 PNS children.Results:(1)The plasma PAF-AH activitywasincrease in PNS children,(2)Significant statistical difference of plasma PAF-AH activity exits in PNS children.The plasma PAF-AH activitywashigher in SNTS than NTNS groups, while it is higher in SSNS groups than that of both SRNS and SDNS group. However,no significant difference of the plasma PAF-AH activity was found between the groups of steroid-dependent nephritic(SDNS)and the normal healthy children.(3)Therewere61cases of Genotype GG,26 cases of Genotype GT and 7 cases of Genotype TT in 94 cases of PNS patients.(4)No significant differences were found to relate the genotype and allele frequencies between patients with PNS and normal controls.(5)It was confirmed that the gene mutation frequencies among patients with NTNS are higher than those of the patients with STNS and normal controls.The gene mutation frequencies of SDNS were higher than that of both SSNS and normal control groups.No significant differences were found related to the gene mutation frequencies between patients with SSNS,SRNS and normal controls.(6)The number of relapse during the first year after onset was significantly higher in the patients who were heterozygous for the mutant allele(GT)or homozygous(TT)than in those of the GG homozygous.(7)Genotype GGwas the most common genotype and TT is the less frequent type. It was sure that the activity of PAF-AH was higher in sick kids with PNS than those healthy children.But there wasno PAF-AH activity difference among the same genotype in PNS patients.(8)There was no difference in the allele frequencies and PAF-AH activity among the MsPGN,FSGS,and MCNS patients.The plasma PAF-AH activity was higher in MsPGN and MCNS than in normal healthy children.The plasma PAF-AH activity was higher in minor MsPGN than in moderate.CONCLUSIONS(1)The plasma PAF-AH activity was significant high in PNS children,and the activity was significant difference in different types of PNS patients.The plasma PAF-AH may participate in the mechanism of PNS.(2)The allele frequencies in the PAF-AH gene were higher in NTNS patients than in STNS patients.(3)No matter in PNS children or in health children,there was a significant relationship between genotypes of PAF-AH and PAF-AH activity.The PAF-AH activity was the highest in genotype GG,and the lowest was genotype TT.It show ed that genotypes of PAF-AH may influence PAF-AH activity.(4)The risk of relapse during the treatment period was higher in patients with PAF-AH gene mutation occurred at position 994.The response to steroid application could been forecast through identifying genotypes of PAF-AH.(5)PAF-AH activity w aslikely correlated to the pathological observations in the pathological type of PNS.