Tedeschi Sara K, Cui Jing, Arkema Elizabeth V, Robinson William H, Sokolove Jeremy, Lingampalli Nithya, Sparks Jeffrey A, Karlson Elizabeth W, Costenbader Karen H
Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, 75 Francis St, Boston, MA 02115.
Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, 75 Francis St, Boston, MA 02115.
Semin Arthritis Rheum. 2017 Jun;46(6):692-698. doi: 10.1016/j.semarthrit.2016.09.001. Epub 2016 Sep 13.
Overweight/obesity and anti-citrullinated protein antibodies (ACPA) increase rheumatoid arthritis (RA) risk. We investigated the relationship between body mass index (BMI) and ACPA, tested for an interaction between BMI and ACPA for RA risk, and examined effects of BMI and ACPA on time to RA diagnosis.
Within the Nurses' Health Studies, blood samples were collected before diagnosis from medical record-confirmed incident RA cases and matched controls. Multiplex assays measured 7 ACPA subtypes (biglycan, clusterin, enolase, fibrinogen, histone 2A, histone 2B, and vimentin). Logistic regression analyses tested the association of BMI and ACPA and for a multiplicative interaction between BMI groups (≥25 vs. <25kg/m) and ACPA positivity (≥2 vs. <2 subtypes), adjusting for age, smoking, alcohol use, and HLA-shared epitope. In case-only analyses, log-rank tests compared time from blood draw to RA onset by cross-classified BMI/ACPA status.
Among 255 pre-RA cases and 778 matched controls, 15.7% vs. 2.1% (p<0.001) had ≥2 ACPA and 49.4% vs. 40.2% (p<0.01) were overweight/obese. Continuous BMI was not associated with presence of ≥2 ACPA [OR per kg/m unit BMI: 1.03 (95% CI: 0.97-1.09)]. However, there was a multiplicative interaction between elevated BMI and the presence of ≥2 ACPA for RA risk (p = 0.027). Women with BMI≥25kg/m and ≥2 ACPA had OR 22.7 (95% CI: 6.64-77.72) for RA. Median time to RA differed by BMI/ACPA group (overall log-rank p<0.001) and was shortest among women with ≥2 ACPA and BMI≥25kg/m [45.0 months, IQR: 17.5-72.5] and longest in women with <2 ACPA and BMI<25kg/m [125.0 months, IQR: 72.0-161.0] (pairwise log-rank p = 0.002).
Elevated BMI and presence of ACPA interacted to increase RA risk. Time to RA onset was shortest among overweight/obese women with ≥2 ACPA.
超重/肥胖和抗瓜氨酸化蛋白抗体（ACPA）会增加类风湿关节炎（RA）的发病风险。我们研究了体重指数（BMI）与ACPA之间的关系，检测了BMI和ACPA在RA风险方面的相互作用，并研究了BMI和ACPA对RA诊断时间的影响。
在护士健康研究中，从病历确诊的新发RA病例和匹配的对照中，在诊断前采集血样。多重检测法检测了7种ACPA亚型（双糖链蛋白聚糖、簇集素、烯醇化酶、纤维蛋白原、组蛋白2A、组蛋白2B和波形蛋白）。逻辑回归分析检测了BMI与ACPA的相关性，以及BMI组（≥25 vs. <25kg/m²）和ACPA阳性（≥2 vs. <2种亚型）之间的相乘相互作用，同时对年龄、吸烟、饮酒和HLA共享表位进行了校正。在仅针对病例的分析中，对数秩检验按交叉分类的BMI/ACPA状态比较了从采血到RA发病的时间。
在255例RA前期病例和778例匹配对照中，≥2种ACPA的比例分别为15.7%和2.1%（p<0.001），超重/肥胖的比例分别为49.4%和40.2%（p<0.01）。连续的BMI与≥2种ACPA的存在无关[每kg/m²单位BMI的OR值：1.03（95%CI：0.97-1.09）]。然而，BMI升高与≥2种ACPA的存在在RA风险方面存在相乘相互作用（p = 0.027）。BMI≥25kg/m²且≥2种ACPA的女性患RA的OR值为22.7（95%CI：6.64-77.72）。RA的中位发病时间因BMI/ACPA组而异（总体对数秩检验p<0.001），在≥2种ACPA且BMI≥25kg/m²的女性中最短[45.0个月，IQR：17.5-72.5]，在<2种ACPA且BMI<25kg/m²的女性中最长[125.0个月，IQR：72.0-161.0]（两两对数秩检验p = 0.002）。
BMI升高和ACPA的存在相互作用会增加RA风险。在超重/肥胖且≥2种ACPA的女性中，RA发病时间最短。
