Surdacki Andrzej, Sulicka Joanna, Korkosz Mariusz, Mikolajczyk Tomasz, Telesinska-Jasiówka Dorota, Klimek Ewa, Kierzkowska Izabella, Guzik Tomasz, Grodzicki Tomasz K
From the Second Department of Cardiology, the Department of Rheumatology and Balneology, the Division of Rheumatology, Department of Internal Medicine and Gerontology, and the Department of Internal and Agricultural Medicine, Jagiellonian University Medical College and University Hospital; and J. Dietl Hospital, Krakow, Poland.
J Rheumatol. 2014 Mar;41(3):481-9. doi: 10.3899/jrheum.130803. Epub 2014 Feb 1.
Ankylosing spondylitis (AS) is associated with excessive cardiovascular (CV) morbidity. Interactions between activated endothelium and monocytes precede atherosclerotic plaques. Our aim was to quantify blood monocyte subsets in relation to endothelial activation and inflammatory activity in subjects with AS who were free of clinical atherosclerotic CV disease.
Markers of inflammation and endothelial activation were measured in 47 patients with AS receiving no disease-modifying antirheumatic drugs, and 22 healthy controls. Exclusion criteria included atherosclerotic CV disease and traditional risk factors. Flow cytometry was used to identify monocyte subsets: classical CD14(++)CD16(-), intermediate CD14(++)CD16(+), and nonclassical CD14(+)CD16(++) monocytes and to evaluate their expression of CD11b and CD11c.
Traditional risk factors were comparable among the groups, except for lower high-density lipoprotein cholesterol in AS (p = 0.007). Relative to controls, in subjects with AS counts of classical monocytes were higher (84.3 ± 5.4 vs 78.9 ± 5.3% of blood monocytes, p < 0.001) and nonclassical monocytes lower (2.9 ± 2.2 vs 5.5 ± 2.3%, p < 0.001). In AS we observed increased soluble intercellular adhesion molecule-1 [251 (224-293) vs 202 (187-230) ng/ml, p = 0.002], an endothelial ligand for monocytic β2-integrin CD11b/CD18. CD11b expression on all 3 monocyte subsets was elevated in 21 AS subjects with a Bath Ankylosing Spondylitis Disease Activity Index score ≥ 4 versus the remaining patients (p = 0.005-0.03). C-reactive protein, interleukin 6 (IL-6), and pentraxin-3 were increased in AS, in contrast to tumor necrosis factor-α and IL-18. IL-6 correlated with classical monocytes numbers in AS (r = 0.56, p < 0.0001) but not in the controls (r = 0.10, p = 0.65).
Our findings suggest a contribution of immune dysregulation to enhanced monocyte-endothelial interactions in AS, especially in patients with active disease, which possibly can accelerate atherogenesis on a longterm basis.
强直性脊柱炎（AS）与心血管（CV）疾病发病率过高相关。活化的内皮细胞与单核细胞之间的相互作用先于动脉粥样硬化斑块形成。我们的目的是对无临床动脉粥样硬化性CV疾病的AS患者的血液单核细胞亚群进行定量分析，以了解其与内皮细胞活化及炎症活动的关系。
对47例未接受改善病情抗风湿药物治疗的AS患者和22名健康对照者进行炎症和内皮细胞活化标志物检测。排除标准包括动脉粥样硬化性CV疾病和传统危险因素。采用流式细胞术鉴定单核细胞亚群：经典型CD14(++)CD16(-)、中间型CD14(++)CD16(+)和非经典型CD14(+)CD16(++)单核细胞，并评估其CD11b和CD11c的表达。
除AS患者高密度脂蛋白胆固醇较低外（p = 0.007），各组间传统危险因素具有可比性。与对照组相比，AS患者经典单核细胞计数较高（占血液单核细胞的84.3 ± 5.4% vs 78.9 ± 5.3%，p < 0.001），而非经典单核细胞计数较低（2.9 ± 2.2% vs 5.5 ± 2.3%，p < 0.001）。在AS患者中，我们观察到可溶性细胞间黏附分子-1升高[251（224 - 293）ng/ml vs 202（187 - 230）ng/ml，p = 0.002]，它是单核细胞β2整合素CD11b/CD18的内皮配体。与其余患者相比，21例巴斯强直性脊柱炎疾病活动指数评分≥4的AS患者的所有3个单核细胞亚群上的CD11b表达均升高（p = 0.005 - 0.03）。与肿瘤坏死因子-α和白细胞介素-18相反，AS患者的C反应蛋白、白细胞介素-6（IL-6）和五聚素-3升高。IL-6与AS患者的经典单核细胞数量相关（r = 0.56，p < 0.0001），但与对照组无关（r = 0.10，p = 0.65）。
我们的研究结果表明免疫失调在AS患者单核细胞-内皮细胞相互作用增强中起作用，尤其是在疾病活动期患者中，这可能长期加速动脉粥样硬化的发生。
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