Alpizar-Rodriguez D, Brulhart Laure, Mueller Ruediger B, Möller Burkhard, Dudler Jean, Ciurea Adrian, Walker Ulrich A, Von Mühlenen Ines, Kyburz Diego, Zufferey Pascal, Mahler Michael, Bas Sylvette, Gascon Danielle, Lamacchia Céline, Roux-Lombard Pascale, Lauper Kim, Nissen Michael J, Courvoisier Delphine S, Gabay Cem, Finckh Axel
Division of Rheumatology, Department of Internal Medicine Specialties, University Hospitals of Geneva, 26, Ave Beau-Sejour, CH 1211, Geneva, Switzerland.
Division of Rheumatology, Immunology and Rehabilitation, Kantonsspital St. Gallen, St. Gallen, Switzerland.
Clin Rheumatol. 2017 Mar;36(3):677-682. doi: 10.1007/s10067-017-3547-3. Epub 2017 Jan 21.
Transition from genetic risk to the development of systemic autoimmunity associated with rheumatoid arthritis (RA) is considered a key step for the development of RA and often referred to as the immune onset of the disease. The aim of this study is to identify predictors for the presence of anticitrullinated protein antibodies (ACPA) as a marker of systemic autoimmunity associated with RA in a high-risk population, an ongoing cohort of first-degree relatives of patients with RA. We assessed the presence of ACPA in individuals without clinical evidence of RA. We examined characteristics associated with ACPA positivity using general estimation equations to account for multiple observations per individual. A total of 1159 serum samples from 1025 subjects were analyzed, 69 samples (6%) were ACPA-positive, and 227 (20%) positive for rheumatoid factor. Participants had a median age of 45 years (interquartile range (IQR): 33-55) at baseline and 76% were women. Overall, ACPA positivity increased with age (p < 0.001). Among women, ACPA positivity was particularly associated with the age group 45 to 55 years (p = 0.003), but not among men (p = 0.7). In multivariable adjusted analyses, age older than 45, female sex and tobacco smoking were independently associated with ACPA positivity. In our cohort, the presence of ACPA was associated with older age and peaked in women around age 45 to 55 years, the perimenopausal period, suggesting that the development of ACPA may be favored by the decline in ovarian function.
从遗传风险转变为与类风湿关节炎（RA）相关的全身性自身免疫的发展被认为是RA发病的关键步骤，常被称为疾病的免疫发病。本研究的目的是在高危人群（即RA患者的一级亲属持续队列）中确定抗瓜氨酸化蛋白抗体（ACPA）作为与RA相关的全身性自身免疫标志物的存在预测因素。我们评估了无RA临床证据个体中ACPA的存在情况。我们使用广义估计方程来考虑个体的多次观察，检查与ACPA阳性相关的特征。共分析了来自1025名受试者的1159份血清样本，69份样本（6%）ACPA呈阳性，227份（20%）类风湿因子呈阳性。参与者基线时的年龄中位数为45岁（四分位间距（IQR）：33 - 55），76%为女性。总体而言，ACPA阳性率随年龄增加而升高（p < 0.001）。在女性中，ACPA阳性尤其与45至55岁年龄组相关（p = 0.003），而在男性中则不然（p = 0.7）。在多变量调整分析中，年龄大于45岁、女性性别和吸烟与ACPA阳性独立相关。在我们的队列中，ACPA的存在与年龄较大相关，且在45至55岁左右（围绝经期）的女性中达到峰值，这表明卵巢功能下降可能有利于ACPA的产生。
