Objectives: 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.
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DSM and KDD contributed equally to the study.
Funding: These studies were supported by R21 AI61479, T32 AR07534, Arthritis Foundation/American College of Rheumatology Physician Scientist Development Award, K12 RR017707, K23 AR051461 and the Smyth Professorship in Rheumatology.
Competing interests: None.
DSM participated in the design and analysis of this study and the writing of this manuscript. KDD participated in the analysis of data and preparation of the manuscript. LAP participated in the analysis of samples and data and preparation of the manuscript. AAL and AEB contributed statistical expertise in the analysis of data for this manuscript. CWW participated in subject evaluation and determination of eligibility for this study. MVR participated in the design of this study and procurement of the serum samples for analysis. WRG participated in the design of this study and procurement of the serum samples for analysis, as well as subject evaluation and determination of eligibility for this study. JMN participated in the design and analysis of this study and preparation of the manuscript. VMH participated in the design and analysis of this study, antibody testing, and manuscript preparation.
Disclaimer: The views expressed in this abstract are those of the authors and do not reflect the official policy of the Department of the Army, Department of Defence, or US Government.
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