Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.
Analysis of Twin Concordance for ACPA Positivity and ACPA fine specificities in a Large Swedish Twin Cohort (TwinGene).
Hensvold1, Aase Haj, Magnusson2, Patrik KE, Hansson1, Monika, Israelsson1, Lena, Carlens1, Cecilia, Holmdahl3, Rikard, Jakobsson1, Per-Johan
Rheumatology unit, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
Swedish Twin Registry Karolinska Institutet, Stockholm, Sweden
Medical Biochemistry and Biophysics Karolinska Institutet, Stockholm, Sweden
Clinical Epidemiology Unit, Dept of Medicine, Karolinska Institutet, Stockholm, Sweden
Both genetic and environmental factors are established risk factors for Anti Citrulline Peptide Antibodies (ACPA) positive rheumatoid arthritis (RA). As ACPA appear before disease onset and are highly specific for RA we aimed to investigate the influence of genetic and environmental factors in ACPA positivity, using a twin study approach.
We used a subset of the Swedish twin registry, which includes 12 594 monozygotic (MZ) and dizygotic (DZ) twins born 1958 or earlier. All blood samples were analyzed for ACPA using a commercial ELISA. All available paired samples (n=312 twin pairs) in which at least one twin was ACPA positive were further investigated for presence of ACPA fine specificities against native and citrullinated forms of alpha-enolase (aa521; cep1), collagen type II (aa359369; citC1), fibrinogen (aa566580; citfib573) and vimentin (aa6075; citvim60) peptides, using a cut off set at the 98 percentile, based on analysis of sera from healthy controls. RA or other rheumatic joint diseases were verified by, data from register linkage to national care registers or by reviewing medical records.
Concordance for ACPA positivity was estimated by casewise concordance and tetrachoric correlation. Odds ratios (OR) to develop ACPA were calculated according to self-reported smoking status and cumulative dose of smoking estimated by pack years. Twins were defined as smokers (n=6252) if they were or had been smoking regularly or occasionally.
387 out of 12 594 tested individuals (3.1%) were positive for ACPA. Smokers had an increased risk of developing ACPA as compared with non-smokers (OR 1.33, 95% CI 1.081.63) and the risk was highest among those smoking more than 10 pack years (OR 1.49, 95% CI 1.181.88).
Among the ACPA positive, 312 twin complete pairs were available, 7 concordant and 305 ACPA discordant pairs. Casewise concordance for ACPA was 6.8% among MZ and 6.2% among DZ twins, with no significant tetrachoric correlation (r MZ twins 0.17, 95% CI -0.100.44, and r DZ twins 0.14, 95% CI -0.100.36).
Her analysis of ACPA fine specificities was performed in the same subgroup of twins. The most common of the analyzed fine specificities was against Cit-enolase (19% of the 624 tested samples). The casewise concordance rate for Cit-enolase was 19% among MZ and 10% among DZ twins, with no significant tetrachoric correlation (r MZ twins 0.17, 95% CI -0.350.69 and r DZ twins -0.32, 95% CI -0.580.07). A majority of ACPA positive twins with a RA diagnosis at the time of inclusion, 77%, were positive for one or more of the tested ACPA fine specificities as opposed to ACPA positive twins without any rheumatic joint disease where only 26% were positive for one or more of the tested ACPA fine specificities.
In this large population-based cohort of middle-aged twins, we found a low concordance rate for ACPA in both MZ and DZ twins. Our results indicate that environment, life style and stochastic factors may be more important than genetics in determining which individuals will develop ACPA, whereas genetic factors may have a larger impact in determining which ACPA-positive individuals that will ultimately develop arthritis.
To cite this abstract, please use the following information:
Hensvold, Aase Haj, Magnusson, Patrik KE, Hansson, Monika, Israelsson, Lena, Carlens, Cecilia, Holmdahl, Rikard, et al; Analysis of Twin Concordance for ACPA Positivity and ACPA fine specificities in a Large Swedish Twin Cohort (TwinGene). [abstract]. Arthritis Rheum 2011;63 Suppl 10 :767