OBJECTIVES: To find out whether autoantibodies to citrullinated telopeptides of type I and II collagens and to cyclic citrullinated peptides (CCPs) predict the development of rheumatoid arthritis (RA). METHODS: A case-control study (matched for sex, age and municipality) was nested within a Finnish cohort of 19072 adults who had neither arthritis nor a history of it at the baseline examination during 1973-7. 124 subjects developed RA by late 1989, and of these, 89 were positive for rheumatoid factor (RF). Preillness serum specimens were analysed for autoantibodies against arginine (A)- or citrulline (C)-containing synthetic telopeptides using a chemiluminescence method and for anti-CCPs Mark2 with an enzyme-linked immunosorbent assay method. RESULTS: The mean levels of autoantibodies to citrulline-containing telopeptides and the C/A ratios of type I and II collagens and to CCP were higher in subjects who later developed RF-positive RA. In the highest tertiles of C/A (I), C/A (II) ratios and anti-CCPs levels, the relative risk of RF-positive RA was significantly increased. In the multifactorial model, only anti-CCPs retained its statistical significance. However, the interaction term of C/A (II) ratio and anti-CCPs proved to be statistically significant (p = 0.02). The subjects ranked into the highest tertiles of both C/A (II) ratio and anti-CCPs had an odds ratio of 20.06 (95% confidence interval, 4.37 to 92.06) of developing RF-positive RA compared with those in the lowest tertiles of these antibodies. None of the autoantibodies predicted RF-negative RA. CONCLUSION: Autoantibodies to citrullinated telopeptides of type I and II collagen and to CCPs exert a synergistic effect on the risk of seropositive RA.
OBJECTIVES: To find out whether autoantibodies to citrullinated telopeptides of type I and II collagens and to cyclic citrullinated peptides (CCPs) predict the development of rheumatoid arthritis (RA). METHODS: A case-control study (matched for sex, age and municipality) was nested within a Finnish cohort of 19072 adults who had neither arthritis nor a history of it at the baseline examination during 1973-7. 124 subjects developed RA by late 1989, and of these, 89 were positive for rheumatoid factor (RF). Preillness serum specimens were analysed for autoantibodies against arginine (A)- or citrulline (C)-containing synthetic telopeptides using a chemiluminescence method and for anti-CCPs Mark2 with an enzyme-linked immunosorbent assay method. RESULTS: The mean levels of autoantibodies to citrulline-containing telopeptides and the C/A ratios of type I and II collagens and to CCP were higher in subjects who later developed RF-positive RA. In the highest tertiles of C/A (I), C/A (II) ratios and anti-CCPs levels, the relative risk of RF-positive RA was significantly increased. In the multifactorial model, only anti-CCPs retained its statistical significance. However, the interaction term of C/A (II) ratio and anti-CCPs proved to be statistically significant (p = 0.02). The subjects ranked into the highest tertiles of both C/A (II) ratio and anti-CCPs had an odds ratio of 20.06 (95% confidence interval, 4.37 to 92.06) of developing RF-positive RA compared with those in the lowest tertiles of these antibodies. None of the autoantibodies predicted RF-negative RA. CONCLUSION: Autoantibodies to citrullinated telopeptides of type I and II collagen and to CCPs exert a synergistic effect on the risk of seropositive RA.
Authors: E R Vossenaar; T R D Radstake; A van der Heijden; M A M van Mansum; C Dieteren; D-J de Rooij; P Barrera; A J W Zendman; W J van Venrooij Journal: Ann Rheum Dis Date: 2004-04 Impact factor: 19.103
Authors: Kendra A Young; Kevin D Deane; Lezlie A Derber; Jan M Hughes-Austin; Catriona A Wagner; Jeremy Sokolove; Michael H Weisman; Jane H Buckner; Ted R Mikuls; James R O'Dell; Richard M Keating; Peter K Gregersen; William H Robinson; V Michael Holers; Jill M Norris Journal: Arthritis Rheum Date: 2013-08