title: [Association between the synovial expression of cyclic citrullinated peptide and susceptibility variants of HLA-DRB1 shared epitope alleles and PADI 4 gene single nucleotide polymorphisms in patients with rheumatoid arthritis].
abstract: OBJECTIVE
  To analyze the association between the synovial expression of cyclic citrullinated peptide (CCP) and susceptibility variants of HLA-DRB1 shared epitope (SE) alleles and/or peptidylarginine deiminase 4 (PADI4) gene single nucleotide polymorphisms (SNP) in patients with rheumatoid arthritis (RA).
  
  
  METHODS
  From October 2008 to December 2011, 53 RA patients and 42 controls were enrolled. The expression of CCP in RA synovial tissues was detected by immunohistochemical assay with 6×His tagged anti-CCP single chain fragment V (ScFv) antibodies generated by pHEN2 phagemid recombinant antibodies display system. PADI4 SNP was genotyped by reverse transcription cDNA sequencing and heterozygote was DNA haplotype was mapped by TA clone sequencing. HLA-DRB1 SE alleles were analyzed by sequence specific primer-polymerase chain reaction (SSP-PCR).
  
  
  RESULTS
  The prevalence of synovial CCP expression was significantly different between RA group and the control (76.9% and 11.4% respectively, P < 0.01). The frequencies of 2 SNPs (PADI4_89 G+ and PADI4_104 T+) varied significantly between the groups(P < 0.05). Compared with the major haplotypes, only these two minor alleles were associated with the increased RA susceptibility (OR = 3.67 and 2.53, P < 0.05). SE+ alleles was strongly associated with RA susceptibility (OR = 5.57, P < 0.01). The synovial expression of CCP in RA was strongly associated with SE+ alleles, only 2 minor SNPs (PADI4_89 G+ and PADI4_104T+) and the combination. Serum anti-CCP titers were significantly associated with SE+ alleles, PADI4_104T+, SE+/PADI4_89 G+ and SE+/PADI4_104T+ haplotype.
  
  
  CONCLUSIONS
  The synovial expression of CCP and the generation of anti-CCP antibodies are strongly associated with SE alleles and/or certain PADI4 gene SNP in RA.
authors.affiliation: Department of Rheumatology, Affiliated Hospital, Inner Mongolia Medical College, Huhhot 010050, China. lhbwb73@gmail.com
authors.forename: Hong-bin
authors.initials: HB
authors.lastname: Li
authors.forename: Ning
authors.initials: N
authors.lastname: Tie
authors.forename: Yong-feng
authors.initials: YF
authors.lastname: Jia
authors.forename: Lin
authors.initials: L
authors.lastname: Shi
authors.forename: Yan
authors.initials: Y
authors.lastname: Su
authors.forename: Gui-zhi
authors.initials: GZ
authors.lastname: Zhang
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.forename: Li-jie
authors.initials: LJ
authors.lastname: Bai
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Zhen
authors.initials: Z
authors.lastname: Xiao
mesh_terms: D000328:Adult; D000483:Alleles; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000276:immunology; D016022:Case-Control Studies; D000939:Epitopes; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D059811:HLA-DRB1 Chains / Q000235:genetics*; D006801:Humans; D006867:Hydrolases / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000276:immunology* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D000080002:Protein-Arginine Deiminase Type 4; D000076342:Protein-Arginine Deiminases; D013583:Synovial Membrane / Q000378:metabolism; D055815:Young Adult
chemical_list: D000939:Epitopes; D059811:HLA-DRB1 Chains; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide; D006867:Hydrolases; C000629235:PADI4 protein, human; D000080002:Protein-Arginine Deiminase Type 4; D000076342:Protein-Arginine Deiminases