Carbone Federico, Satta Nathalie, Montecucco Fabrizio, Virzi Julien, Burger Fabienne, Roth Aline, Roversi Gloria, Tamborino Carmine, Casetta Ilaria, Seraceni Silva, Trentini Alessandro, Padroni Marina, Dallegri Franco, Lalive Patrice H, Mach François, Fainardi Enrico, Vuilleumier Nicolas
First Clinic of Internal Medicine, Department of Internal Medicine, School of Medicine, University of Genoa, Genoa, Italy.
Division of Laboratory Medicine, Department of Genetics and Laboratory Medicine, Geneva University Hospitals, Geneva, Switzerland.
Eur J Clin Invest. 2016 Sep;46(9):805-17. doi: 10.1111/eci.12664.
Autoantibodies to apolipoprotein A-1 (anti-ApoA-1 IgG) were shown to predict major adverse cardiovascular events and promote atherogenesis. However, their potential relationship with clinical disability and ischaemic lesion volume after acute ischaemic stroke (AIS) remains unexplored.
We included n = 76 patients admitted for AIS and we investigated whether baseline serum anti-ApoA-1 IgG levels could predict (i) AIS-induced clinical disability [assessed by the modified Rankin Scale (mRS)], and (ii) AIS-related ischaemic lesion volume [assessed by Computed Tomography (CT)]. We also evaluated the possible pro-apoptotic and pro-necrotic effects of anti-ApoA-1 IgG on human astrocytoma cell line (U251) using flow cytometry.
High levels of anti-ApoA-1 IgG were retrieved in 15·8% (12/76) of patients. Increased baseline levels of anti-ApoA-1 IgG were independently correlated with worse mRS [β = 0·364; P = 0·002; adjusted odds ratio (OR): 1·05 (95% CI 1·01-1·09); P = 0·017] and CT-assessed ischaemic lesion volume [β = 0·333; P < 0·001; adjusted OR: 1·06 (95% CI 1·01-1·12); P = 0·048] at 3 months. No difference in baseline clinical, biochemical and radiological characteristics was observed between patients with high vs. low levels of anti-ApoA-1 IgG. Incubating human astrocytoma cells with anti-ApoA-1 IgG dose dependently induced necrosis and apoptosis of U251 cells in vitro.
Anti-ApoA-1 IgG serum levels at AIS onset are associated with poorer clinical recovery and worse brain lesion volume 3 months after AIS. These observations could be partly explained by the deleterious effect of anti-ApoA-1 IgG on human brain cell survival in vitro and may have clinical implication in the prediction of poor outcome in AIS.
载脂蛋白A-1自身抗体(抗ApoA-1 IgG)已被证明可预测主要不良心血管事件并促进动脉粥样硬化形成。然而,它们与急性缺血性卒中(AIS)后临床残疾和缺血性病变体积之间的潜在关系仍未得到探索。
我们纳入了n = 76例因AIS入院的患者,并研究了基线血清抗ApoA-1 IgG水平是否能够预测:(i)AIS所致的临床残疾[通过改良Rankin量表(mRS)评估],以及(ii)AIS相关的缺血性病变体积[通过计算机断层扫描(CT)评估]。我们还使用流式细胞术评估了抗ApoA-1 IgG对人星形细胞瘤细胞系(U251)可能的促凋亡和促坏死作用。
15.8%(12/76)的患者抗ApoA-1 IgG水平较高。抗ApoA-1 IgG基线水平升高与3个月时较差的mRS[β = 0.364;P = 0.002;校正比值比(OR):1.05(95%可信区间1.01 - 1.09);P = 0.017]以及CT评估的缺血性病变体积[β = 0.333;P < 0.001;校正OR:1.06(95%可信区间1.01 - 1.12);P = 0.048]独立相关。抗ApoA-1 IgG水平高与低的患者之间,在基线临床、生化和放射学特征方面未观察到差异。用抗ApoA-1 IgG孵育人星形细胞瘤细胞在体外剂量依赖性地诱导U251细胞坏死和凋亡。
AIS发病时的抗ApoA-1 IgG血清水平与AIS后3个月较差的临床恢复和更严重的脑病变体积相关。这些观察结果可能部分归因于抗ApoA-1 IgG在体外对人脑细胞存活的有害作用,并且可能对AIS不良预后的预测具有临床意义。