Unit of Immunology and Chronic Disease, Division of Physiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Clin Exp Immunol. 2013 Dec;174(3):441-8. doi: 10.1111/cei.12181.
The risk of premature death is high in haemodialysis (HD) patients. Antibodies against cardiolipin (anti-CL) are thrombogenic in diseases such as systemic lupus erythematosus (SLE). CL is easily oxidized (Ox) and plays a role in apoptosis. In this work we studied immunoglobulin (Ig)M anti-CL and anti-OxCL in HD-patients. We conducted an observational study with a prospective follow-up examining the relationship between anti-CL, anti-OxCL and mortality risk in a well-characterized cohort of 221 prevalent HD patients [56% men, median age 66 (interquartile range 51-74) years, vintage time 29 (15-58) months] with a mean follow-up period of 41 (20-48 months). According to the receiver operator characteristic (ROC) analysis, anti-OxCL [area under the curve (AUC) 0·62, P < 0·01], but not anti-CL (AUC 0·52, P = 0·2), is associated with mortality. In crude and adjusted Cox analysis, every log increase in anti-OxCL inversely predicted all-cause [adjusted hazard ratios (HR) 0·62 (0·43-0·89)] and CVD-related [adjusted HR 0·56 (0·32-0·98)] mortality. Patients with anti-OxCL levels below median also had increased all-cause and cardiovascular disease (CVD)-related mortality. Although anti-OxCL and anti-phosphorylcholine (PC) were related positively to each other (ρ = 0·57, P < 0·01), patients with one or two of these autoantibody levels below the median were associated with an incrementally increased death risk. Anti-OxCL were co-factor β2-GPI-independent; anti-CL from patients with anti-phospholipid antibody syndrome were β2-GPI-dependent, while sera from HD-patients less so. Sera from healthy donors was not β2-GPI-dependent. Anti-OxCL IgM is β2-glycoprotein 1 (GPI)-independent and a novel biomarker; low levels are associated with death among HD patients (and high levels with decreased risk). Combination with anti-PC increases this association. Putative therapeutic implications warrant further investigation.
在血液透析（HD）患者中，过早死亡的风险很高。抗心磷脂（anti-CL）抗体在红斑狼疮（SLE）等疾病中具有血栓形成作用。CL 很容易被氧化（Ox），并在细胞凋亡中发挥作用。在这项工作中，我们研究了 HD 患者中的 IgM 抗-CL 和抗-OxCL。我们进行了一项观察性研究，前瞻性随访了 221 例典型 HD 患者（56%为男性，中位年龄 66（51-74）岁，治疗时间 29（15-58）个月），平均随访时间为 41（20-48）个月），研究了抗-CL、抗-OxCL 与死亡率之间的关系。根据接收者操作特征（ROC）分析，抗-OxCL[曲线下面积（AUC）0·62，P<0·01]，而不是抗-CL（AUC 0·52，P=0·2）与死亡率相关。在未经调整和调整后的 Cox 分析中，抗-OxCL 每增加一个对数，全因死亡的风险就会降低[调整后的危害比（HR）0·62（0·43-0·89）]和心血管疾病（CVD）相关死亡的风险[调整后的 HR 0·56（0·32-0·98）]。抗-OxCL 水平低于中位数的患者也有更高的全因死亡和心血管疾病（CVD）相关死亡风险。尽管抗-OxCL 和抗磷酰胆碱（PC）之间存在正相关（ρ=0·57，P<0·01），但这些自身抗体中有一种或两种水平低于中位数的患者，其死亡风险会逐渐增加。抗-OxCL 与β2-糖蛋白 I 无关；抗磷脂抗体综合征患者的抗-CL 依赖于β2-糖蛋白 I，而 HD 患者的抗-CL 则不然。健康供体的血清不依赖于β2-糖蛋白 I。抗-OxCL IgM 与β2-糖蛋白 1（GPI）无关，是一种新的生物标志物；低水平与 HD 患者的死亡相关（高水平与风险降低相关）。与抗-PC 结合可增加这种关联。进一步的治疗意义值得进一步研究。
