RESEARCH - Duration of preclinical RA-related autoantibody positivity increases in subjects with older age at time of disease diagnosis

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Published Online First: 1 November 2007. doi:10.1136/ard.2007.076679

ls of the Rheumatic Diseases 2008;67:801-807

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EXTENDED REPORTS

Duration of preclinical rheumatoid arthritis-related autoantibody

positivity increases in subjects with older age at time of disease

diagnosis

D S Majka 1, K D Deane 2, L A Parrish 2, A A Lazar 3, A E Barón 3, C W

4, M V Rubertone 5, W R Gilliland 4, J M Norris 3, V M Holers 2

1 Division of Rheumatology, Northwestern University, Feinberg School

of Medicine, Chicago, Illinois, USA

2 Division of Rheumatology, University of Colorado at Denver and

Health Sciences Center, Denver, Colorado, USA

3 Department of Preventive Medicine and Biometrics, University of

Colorado at Denver and Health Sciences Center, Denver, Colorado, USA

4 Department of Medicine, Rheumatology Section, Walter Army

Medical Center, Washington DC, USA

5 US Army Center for Health Promotion and Preventive Medicine,

Washington, DC, USA

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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http://ard.bmj.com/cgi/content/abstract/67/6/801?etoc

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