Pereira Ivânio, Laurindo Ieda, Burlingame Rufus, Anjos Lisiane, Viana Vilma, Leon Elaine, Vendramini Margareth, Borba Eduardo
Rheumatology Division, University of Santa Catarina, Santa Catarina, Brazil.
Joint Bone Spine. 2008 Jul;75(4):416-21. doi: 10.1016/j.jbspin.2008.01.022. Epub 2008 May 23.
Many questions remain unanswered about premature atherosclerosis in rheumatoid arthritis (RA). Besides inflammation, some studies have suggested the role of autoantibodies on its pathogenesis.
The aim of this study was to investigate the presence of antibodies against phospholipids, beta2-glycoprotein1 (beta2-gp1), lipoprotein lipase, and heat shock proteins (Hsp) in RA patients and to evaluate their possible association with subclinical carotid atherosclerosis.
Seventy-one RA patients and 53 age- and sex-matched controls were selected to perform anticardiolipin antibodies (aCL) (IgG and IgM), anti-beta2-gp1 (IgG, IgM, and IgA), anti-lipoprotein lipase (anti-LPL), anti-Hsp 60, and anti-Hsp 65 by ELISA tests. Intima-medial thickness (IMT) of common carotid and presence of plaques were assessed by high-resolution B-mode ultrasonography. Exclusion criteria were smoking, diabetes, and arterial hypertension. Lipoproteins, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and fibrinogen levels, as well as health assessment questionnaire (HAQ) and disease activity score (DAS) 28 were also evaluated.
Age (48.93+/-12.31 vs. 45.37+/-9.37 years; p=0.20) and body mass index (BMI) (p=0.69) were similar in RA and controls, as well as female gender (p=0.56). The mean IMT was similar between RA and controls (0.721+/-0.16 vs. 0.667+/-0.14 mm, p=0.07) but the frequency of plaques was higher in RA (14.1% vs. 1.9%; p=0.02). In RA patients, IMT measurements did not differ according to the presence or absence of these antibodies: IgG aCL (0.62+/-0.64 vs. 0.72+/-0.17 mm, p=0.24), IgM aCL (0.65+/-0.79 vs. 0.73+/-0.17 mm, p=0.33), anti-Hsp 60 (0.78+/-0.20 vs. 0.71+/-0.16 mm, p=0.27), anti-Hsp 65 (0.73+/-0.16 vs. 0.72+/-0.17 mm, p=0.77), IgG anti-beta2-gp1 (0.73+/-0.16 vs. 0.71+/-0.17 mm, p=0.72), and anti-CCP (0.71+/-0.16 vs. 0.76+/-0.20mm, p=0.36). In addition, IMT did not correlate with antibodies titers: IgG aCL (r=-0.09, p=0.47), IgM aCL (r=-0.15, p=0.21), anti-Hsp 60 (r=0.10, p=0.42), anti-Hsp 65 (r=0.05, p=0.69), IgG anti-beta2-gp1 (r=-0.07, p=0.57), IgM anti-beta2-gp1 (r=-0.05, p=0.69), IgA anti-beta2-gp1 (r=0.03, p=0.79), and anti-CCP (r=-0.07, p=0.57). RA patients with plaques had a significantly higher age compared to those without plaques (p=0.001), as well as higher mean IMT (p<0.001), total cholesterol (p=0.001), and LDL (p=0.003).
In RA a clear association between all autoantibodies studied herein and increased IMT or presence of plaques was not observed. The great prevalence of carotid atherosclerosis in RA was related to age, total and LDL cholesterol, as identified in normal population.
关于类风湿关节炎（RA）患者过早发生动脉粥样硬化仍有许多问题未得到解答。除炎症外，一些研究提示自身抗体在其发病机制中发挥作用。
本研究旨在调查RA患者中抗磷脂、β2糖蛋白1（β2-gp1）、脂蛋白脂肪酶及热休克蛋白（Hsp）抗体的存在情况，并评估其与亚临床颈动脉粥样硬化的可能关联。
选取71例RA患者及53例年龄和性别匹配的对照，采用酶联免疫吸附试验（ELISA）检测抗心磷脂抗体（aCL）（IgG和IgM）、抗β2-gp1（IgG、IgM和IgA）、抗脂蛋白脂肪酶（抗LPL）、抗Hsp 60及抗Hsp 65。采用高分辨率B型超声评估颈总动脉内膜中层厚度（IMT）及斑块情况。排除标准为吸烟、糖尿病及动脉高血压。同时评估脂蛋白、红细胞沉降率（ESR）、C反应蛋白（CRP）、纤维蛋白原水平，以及健康评估问卷（HAQ）和疾病活动评分（DAS）28。
RA患者与对照组在年龄（48.93±12.31岁 vs. 45.37±9.37岁；p=0.20）、体重指数（BMI）（p=0.69）及女性比例（p=0.56）方面相似。RA患者与对照组的平均IMT相似（0.721±0.16 vs. 0.667±0.14 mm，p=0.07），但RA患者斑块发生率更高（14.1% vs. 1.9%；p=0.02）。在RA患者中，IMT测量值在有或无这些抗体的患者间无差异：IgG aCL（0.62±0.64 vs. 0.72±0.17 mm，p=0.24）、IgM aCL（0.65±0.79 vs. 0.73±0.17 mm，p=0.33）、抗Hsp 60（0.78±0.20 vs. 0.71±0.16 mm，p=0.27）、抗Hsp 65（0.73±0.16 vs. 0.72±0.17 mm，p=0.77）、IgG抗β2-gp1（0.73±0.16 vs. 0.71±0.17 mm，p=0.72）及抗环瓜氨酸肽（抗CCP）（0.71±0.16 vs. 0.76±0.20mm，p=0.36）。此外，IMT与抗体滴度无相关性：IgG aCL（r=-0.09，p=0.47）、IgM aCL（r=-0.15，p=0.21）、抗Hsp 60（r=0.10，p=0.42）、抗Hsp 65（r=0.05，p=0.69）、IgG抗β2-gp1（r=-0.07，p=0.57）、IgM抗β2-gp1（r=-
