Objectives: This study investigated factors that may influence the prevalence and timing of appearance of rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies during the pre-clinical phase of rheumatoid arthritis (RA) development.
Methods: 243 serial pre-diagnosis serum samples from 83 subjects with RA were examined for the presence of RF and anti-CCP antibodies.
Results: 57% and 61% of subjects had at least one pre-diagnosis sample positive for RF or anti-CCP, respectively. Gender and race were not significantly associated with the prevalence or timing of pre-clinical antibody appearance. Pre-clinical anti-CCP positivity was strongly associated with the development of erosive RA (OR 4.64; 95% CI 1.71-12.63; p=0.003), but RF was not (p=0.11). Additionally, as age at the time of diagnosis of RA increased the duration of pre-diagnosis antibody positivity for RF and anti-CCP increased, with the longest duration of pre-clinical 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 prior to diagnosis lengthens as the age at the time of diagnosis of RA increases. This finding suggests that factors such as genetic risk or environmental exposures influencing the temporal relationship between the development of RA-related autoantibodies and clinically-apparent disease onset may differ with age.
- anti-cyclic citrullinated peptide antibodies
- pre-clinical autoimmunity
- rheumatoid arthritis
- rheumatoid factor