title: Duration of preclinical rheumatoid arthritis-related autoantibody positivity increases in subjects with older age at time of disease diagnosis.
abstract: OBJECTIVE
  To investigate factors that may influence the prevalence and timing of appearance of rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies during the preclinical phase of rheumatoid arthritis (RA) development.
  
  
  METHODS
  243 serial prediagnosis serum samples from 83 subjects with RA were examined for the presence of RF and anti-CCP antibodies.
  
  
  RESULTS
  Of the 83 cases, 47 (57%) and 51 (61%) subjects had at least one prediagnosis sample positive for RF or anti-CCP, respectively. Gender and race were not significantly associated with the prevalence or timing of preclinical antibody appearance. Preclinical anti-CCP positivity was strongly associated with the development of erosive RA (odds ratio = 4.64; 95% confidence interval 1.71 to 12.63; p<0.01), but RF was not (p = 0.60). Additionally, as age at the time of diagnosis of RA increased the duration of prediagnosis antibody positivity for RF and anti-CCP increased, with the longest duration of preclinical antibody positivity seen in patients diagnosed with RA over the age of 40. In no subjects did symptom onset precede the appearance of RF or anti-CCP antibodies.
  
  
  CONCLUSIONS
  The period of time that RF and anti-CCP are present before diagnosis lengthens as the age at the time of diagnosis of RA increases. This finding suggests that factors such as genetic risk or environmental exposure influencing the temporal relationship between the development of RA-related autoantibodies and clinically apparent disease onset may differ with age.
authors.affiliation: Division of Rheumatology, Northwestern University, Feinberg School of Medicine, Chicago, Illinois, USA.
authors.forename: D S
authors.initials: DS
authors.lastname: Majka
authors.forename: K D
authors.initials: KD
authors.lastname: Deane
authors.forename: L A
authors.initials: LA
authors.lastname: Parrish
authors.forename: A A
authors.initials: AA
authors.lastname: Lazar
authors.forename: A E
authors.initials: AE
authors.lastname: Barón
authors.forename: C W
authors.initials: CW
authors.lastname: Walker
authors.forename: M V
authors.initials: MV
authors.lastname: Rubertone
authors.forename: W R
authors.initials: WR
authors.lastname: Gilliland
authors.forename: J M
authors.initials: JM
authors.lastname: Norris
authors.forename: V M
authors.initials: VM
authors.lastname: Holers
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000276:immunology; D001323:Autoantibodies / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000276:immunology*; D012217:Rheumatoid Factor / Q000097:blood*; D016019:Survival Analysis; D013997:Time Factors
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide; D012217:Rheumatoid Factor