title: The impact of genes on the occurrence of autoantibodies in rheumatoid arthritis. A study on disease discordant twin pairs.
abstract: OBJECTIVE
  To assess the genetic effect on the occurrence of rheumatoid arthritis (RA) associated autoantibodies.
  
  
  METHODS
  A co-twin control study of 27 monozygotic (MZ) and 51 dizygotic same sexed (DZss) RA discordant twins.
  
  
  METHODS
  The probandwise concordance rate of anti-keratin antibodies (AKA), anti-cyclic citrullinated peptide antibodies (ACPA), IgA- and IgM rheumatoid factor (IgA-RF and IgM-RF). The odds ratio for these autoantibodies based on both conditional and unconditional logistic regression adjusting for the two major genetic risk factors as well as smoking.
  
  
  RESULTS
  The probandwise concordance rates (95% CI) of ACPA, AKA, IgM-RF and IgA-RF were 78.6 (55.4-92.4), 16.7 (0.6-58.4), 30.0 (7.3-60.6), 42.1 (14.5-71.1) in MZ twins and 25.0 (10.3-44.4), 0.0 (0.0-27.7), 10.5 (1.4-31.5) and 22.2 (6.8-45.0) in DZss twins. In twin pairs discordant for both RA and autoantibodies the OR of ACPA, AKA, IgM-RF and IgA-RF was 5 (0.5-236.5) 9 (1.3-394.5) 272 (3.5-593.2) and 10 (1.4-434.0) in MZ twin pairs and 17 (4.4-146.1) 20 (3.2-828.0) 33 (5.5-1342.4) and 577 (7.4-1149.2) in DZss twin pairs. In multiple logistic regression analysis on ACPA, the MZ/DZ OR was 21.1 (3.3-213.5) when adjusting for age, sex, ever smoking, PTPN22 1858 T-allele, Shared Epitope (SE) and SE-smoking interaction.
  
  
  CONCLUSIONS
  There is a genetic contribution to ACPA generation independent of both SE and PTPN22 1858 T-allele. Environmental factors may trigger the expression of IgA-RF, ACPA and AKA in healthy persons who are predisposed to RA.
authors.affiliation: The Danish Twin Registry, Epidemiology, Institute of Public Health, University of Southern Denmark, Denmark. asvendsen@health.sdu.dk
authors.forename: Anders J
authors.initials: AJ
authors.lastname: Svendsen
authors.forename: Jacob V
authors.initials: JV
authors.lastname: Hjelmborg
authors.forename: Kirsten O
authors.initials: KO
authors.lastname: Kyvik
authors.forename: Gunnar
authors.initials: G
authors.lastname: Houen
authors.forename: Christian
authors.initials: C
authors.lastname: Nielsen
authors.forename: Axel
authors.initials: A
authors.lastname: Skytthe
authors.forename: Peter
authors.initials: P
authors.lastname: Junker
mesh_terms: D000368:Aged; D000483:Alleles; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000235:genetics* / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D004200:Diseases in Twins / Q000097:blood / Q000235:genetics / Q000276:immunology; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D059811:HLA-DRB1 Chains / Q000235:genetics; D006801:Humans; D007633:Keratins / Q000276:immunology; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010456:Peptides, Cyclic / Q000276:immunology; D020641:Polymorphism, Single Nucleotide; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22 / Q000235:genetics / Q000276:immunology; D012217:Rheumatoid Factor / Q000276:immunology; D012907:Smoking / Q000276:immunology; D014429:Twins, Dizygotic / Q000235:genetics; D014430:Twins, Monozygotic / Q000235:genetics
chemical_list: D001323:Autoantibodies; D059811:HLA-DRB1 Chains; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide; D007633:Keratins; D012217:Rheumatoid Factor; C516765:PTPN22 protein, human; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22