Dissertation
Dissertation > Medicine, health > Internal Medicine > Systemic disease > Autoimmune diseases > Autoimmune diseases, connective tissue disease > Rheumatoid arthritis

Study of the Effect of Peptidylarginine Deiminase Ⅳ on Rheumatoid Arthritis

Author LuTianBao
Tutor FanLieYing
School Tongji University
Course Clinical Laboratory Science
Keywords Arthritis rheumatoid peptidylarginine deiminases HLA-DRB1 gene shared epitope cyclic citrullinated peptide
CLC R593.22
Type Master's thesis
Year 2007
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Rheumatoid arthritis(RA)is a systemic,chronic inflammatory disease, affecting~1%of the population,which primarily involves the joints and has features of autoimmunity.The etiology of RA is still unknown.In general,RA is believed to be a complex,multifarious disease that is influenced by both genetic and environmental factors.Previous studies have shown that variability of human leukocyte antigen(HLA) -DRB1 gene is relate susceptibility to RA,especially with the gene of shared epitope (SE).Recently,some studies have shown that anticitrullinating autoantibodies are specific for RA and arise early in the disease course,suggesting that they may have a pathogenic role.The peptidylarginine deiminases(PADIs)genes encode enzymes responsible for the posttranslational conversion of arginine residues into citrulline.A novel association between RA and the peptidyl arginine deiminase type 4 gene (PADI4)was recently proposed,and variability of the peptidyl arginine deiminase type 4 gene may have a specific role in the pathogenesis of the disease.Methods:(1)Sequence-specific primers polymerase chain reaction(PCR-SSP) was used to analysis the SE of HLA-DRB1 gene.(2)CCP were tested by an enzyme linked immunosorbent assay(ELISA)to find its value in the diagnosis in RA,and its relation with the SE of HLA-DRB1 gene and RF.(3)Used real-time quantitative reverse transcription(RT-PCR)researched the gene expression of peptidylarginine deiminaseⅣ,and the relation with the SE of HLA-DRB1 gene.(4)To research the relation of variability of single nucleotide polymorphisms(SNPs)gene with the SE of HLA-DRB1 gene and RA through detecting the sequence of PADI4.The result of our study indicated that:(1)In RA,the positive of SE(86.59%) was significantly higher than the negative(54.36%),and the positive of homozygote (49.30%)was significantly higher than the heterzygote(33.33%).(2)The positive of CCP(82.93%)and RF(76.83%)was no significant association,but the specificity of CCP(97.99%)was significantly higher than the RF(86.58%).The detection of CCP is useful for the diagnosis of RA,especially combined with RF.And the appearance of CCP is no relation with the SE and RF.(3)The expression level of PADI4 gene in RA was significantly higher than the healthy,and the positive of SE was significantly higher than the negative in RA.(4)The frequencies of four PADI4 SNPs alleles (padi489、padi490、padi492、padi4104)were significantly difference,and genotype s carrying the minor alleles and HLA-DRB1 SE alleles were also significantly difference.According to the result,we know that the SE is relative with the RA,and the SE homozygote is associated with increased RA susceptibility.CCP is a valuable diagnostic tool and a useful additional marker for RA.The SE is no relation with the existence of CCP.The PADI4 gene is associated with susceptibility to RA,its level of expression is relative with RA susceptibility,and the SE can effect its expression.The variability of PADI4 SNPs is relative with the susceptibility of RA.The alleles of SE and PADI4 SNPs may have an important role in RA.

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