Kim Ki-Jo, Baek In-Woon, Yoon Chong-Hyeon, Kim Wan-Uk, Cho Chul-Soo
Division of Rheumatology, St. Vincent Hospital, The Catholic University of Korea, Suwon, Republic of Korea.
Division of Rheumatology, Yeouido St. Mary's Hospital, The Catholic University of Korea, Seoul, Republic of Korea.
Clin Exp Rheumatol. 2017 Sep-Oct;35(5):823-830. Epub 2017 Apr 18.
The CD40L/CD40 pathway is involved in the pathophysiology of atherothrombotic disease, and elevated levels of soluble CD40L (sCD40L) were reported in SLE patients. However, the clinical implication of sCD40L in SLE remains elusive.
We measured levels of plasma sCD40L in 241 SLE patients and 37 healthy controls and investigated its association with clinical manifestation and laboratory parameters.
Levels of plasma sCD40L in SLE patients were significantly elevated compared with healthy controls (p=0.013) and positively correlated with levels of soluble P-selectin (γ=0.336, p<0.001). SLE patients who experienced arterial thrombosis had a higher level of sCD40L than those who did not (p=0.029). Plasma sCD40L levels were positively correlated with the titers of anti-cardiolipin and anti-β2 glycoprotein I antibodies (γ=0.338, p<0.001 and γ=0.364, p<0.001, respectively). Its levels were also significantly higher in patients with clinical antiphospholipid syndrome (APS) than in non-APS patients, irrespective of antiphospholipid antibody (aPL) positivity. Of those with arterial thrombosis, sCD40L levels were significantly elevated in patients with positive aPL, compared to those with negative aPL (p=0.011). Multiple regression analysis revealed that the presence of hypertension and positive aPL were independently associated with the occurrence of arterial thrombosis in SLE patients. A parallel analysis showed that sCD40L was also an independent variable for arterial thrombosis; however, this association disappeared when aPL, a strong variable, was included in the model because of collinearity between aPL and sCD40L.
Plasma sCD40L levels were elevated in SLE patients who had positive aPL and experienced arterial thrombosis, suggesting that enhanced release of sCD40L through platelet activation presumably by aPL could contribute to the development of atherothrombotic disease.
CD40L/CD40通路参与动脉粥样硬化血栓形成性疾病的病理生理过程，且有报道称系统性红斑狼疮（SLE）患者可溶性CD40L（sCD40L）水平升高。然而，sCD40L在SLE中的临床意义仍不明确。
我们检测了241例SLE患者和37例健康对照者的血浆sCD40L水平，并研究其与临床表现和实验室参数的相关性。
与健康对照相比，SLE患者的血浆sCD40L水平显著升高（p = 0.013），且与可溶性P-选择素水平呈正相关（γ = 0.336，p < 0.001）。发生动脉血栓形成的SLE患者的sCD40L水平高于未发生者（p = 0.029）。血浆sCD40L水平与抗心磷脂抗体和抗β2糖蛋白I抗体滴度呈正相关（分别为γ = 0.338，p < 0.001和γ = 0.364，p < 0.001）。无论抗磷脂抗体（aPL）是否阳性，临床抗磷脂综合征（APS）患者的sCD40L水平也显著高于非APS患者。在发生动脉血栓形成的患者中，aPL阳性患者的sCD40L水平显著高于aPL阴性患者（p = 0.011）。多元回归分析显示，高血压的存在和aPL阳性与SLE患者动脉血栓形成的发生独立相关。平行分析表明，sCD40L也是动脉血栓形成的一个独立变量；然而，由于aPL与sCD40L之间存在共线性，当将aPL（一个强变量）纳入模型时，这种关联消失。
aPL阳性且发生动脉血栓形成的SLE患者血浆sCD40L水平升高，提示可能由aPL介导的血小板激活导致sCD40L释放增加，这可能促进动脉粥样硬化血栓形成性疾病的发展。
