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. 2008 Jun;67(6):801-7.
doi: 10.1136/ard.2007.076679. Epub 2007 Nov 1.

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, L A Parrish, A A Lazar, A E Barón, C W Walker, M V Rubertone, W R Gilliland, J M Norris, V M Holers
Affiliations

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

D S Majka et al. Ann Rheum Dis. 2008 Jun.

Abstract

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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Conflict of interest statement

COMPETING INTERESTS

The authors declare that they have no competing interests.

Figures

Figure 1
Figure 1. Survival curves showing the timing of appearance of antibodies prior to diagnosis of rheumatoid arthritis, stratified by age at time of diagnosis
Survival analysis with left and interval censoring using all subjects with pre-diagnosis antibody positivity was performed in the RA cases to calculate the median time of appearance of antibodies in subjects. Subjects with positive antibodies prior to diagnosis were included (N = 47 for RF (>15.2 IU/mL) and N = 51 for anti-CCP). Time of diagnosis is at far right of figures, listed as time ‘0’. In each graph, the Y-axis (1-CDF) represents the proportion of cases with antibody positivity in each group based on interval censored survival analysis. Figure 1a: Time of appearance of RF for each age group. Figure 1b: Time of appearance of anti-CCP for each age group.
Figure 1
Figure 1. Survival curves showing the timing of appearance of antibodies prior to diagnosis of rheumatoid arthritis, stratified by age at time of diagnosis
Survival analysis with left and interval censoring using all subjects with pre-diagnosis antibody positivity was performed in the RA cases to calculate the median time of appearance of antibodies in subjects. Subjects with positive antibodies prior to diagnosis were included (N = 47 for RF (>15.2 IU/mL) and N = 51 for anti-CCP). Time of diagnosis is at far right of figures, listed as time ‘0’. In each graph, the Y-axis (1-CDF) represents the proportion of cases with antibody positivity in each group based on interval censored survival analysis. Figure 1a: Time of appearance of RF for each age group. Figure 1b: Time of appearance of anti-CCP for each age group.
Figure 2
Figure 2. Median duration of pre-diagnosis rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibody positivity by age-at-diagnosis groups
Times of appearance are calculated using all antibody positive subjects with interval and left censored survival analysis. Figure 2a. Trend analysis shows significant increase in duration of pre-diagnosis RF positivity (>15.2 IU/mL) as age-at-diagnosis increases (p=0.03). Figure 2b. For anti-CCP, trend analysis for increased duration of pre-diagnosis anti-CCP positivity as age-at-diagnosis increases was marginally significant (p=0.07). This latter finding may be due to small sample sizes or may suggests possible non-linear trend in duration of pre-clinical antibody positivity.
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