Koivula Marja-Kaisa, Heliövaara Markku, Ramberg Jarmo, Knekt Paul, Rissanen Harri, Palosuo Timo, Risteli Juha
Department of Clinical Chemistry, University of Oulu and University of Turku, Oulu and Turku, Finland.
Ann Rheum Dis. 2007 Nov;66(11):1450-5. doi: 10.1136/ard.2006.062919. Epub 2007 May 1.
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).
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.
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.
Autoantibodies to citrullinated telopeptides of type I and II collagen and to CCPs exert a synergistic effect on the risk of seropositive RA.
探究抗I型和II型胶原瓜氨酸化端肽及抗环瓜氨酸肽（CCP）自身抗体能否预测类风湿关节炎（RA）的发生。
一项病例对照研究（按性别、年龄和城市匹配）嵌套于芬兰一个由19072名成年人组成的队列中，这些人在1973 - 1977年的基线检查时既无关节炎也无关节炎病史。到1989年末，有124名受试者患上RA，其中89名类风湿因子（RF）呈阳性。采用化学发光法分析发病前血清标本中针对含精氨酸（A）或瓜氨酸（C）的合成端肽的自身抗体，并采用酶联免疫吸附测定法分析抗CCP Mark2。
后来发展为RF阳性RA的受试者中，抗含瓜氨酸端肽自身抗体的平均水平以及I型和II型胶原的C/A比值及抗CCP水平更高。在C/A（I）、C/A（II）比值和抗CCP水平的最高三分位数中，RF阳性RA 的相对风险显著增加。在多因素模型中，只有抗CCP保留了其统计学意义。然而，C/A（II）比值与抗CCP的交互项被证明具有统计学意义（p = 0.02）。与这些抗体最低三分位数的受试者相比，C/A（II）比值和抗CCP均处于最高三分位数的受试者发生RF阳性RA的比值比为20.06（95%置信区间，4.37至92.06）。没有一种自身抗体能预测RF阴性RA。
抗I型和II型胶原瓜氨酸化端肽及抗CCP自身抗体对血清阳性RA的风险具有协同作用。
