Samal Shailesh Kumar, Qureshi Abdul Rashid, Rahman Mizanur, Stenvinkel Peter, Frostegård Johan
Unit of Immunology and Chronic Disease, Institute of Environmental Medicine, Karolinska Institutet, 17177 Stockholm, Sweden.
Divisions of Renal Medicine, Department of Clinical Science, Intervention and Technology, 14152 Huddinge, Sweden.
J Clin Med. 2020 Mar 11;9(3):753. doi: 10.3390/jcm9030753.
Patients on haemodialysis (HD-patients) have an increased risk of premature death. Low levels of IgM antibodies against malondialdehyde (anti-MDA) are associated with increased risk of cardiovascular disease (CVD) with underlying potential mechanisms described. Here, we studied subclasses and isotypes of anti-MDA in 210 HD-patients with mortality as outcome (56% men, median age 66, Interquartile range (IQR) 51-74 years, vintage time 29 (15-58) months, mean follow up period of 41 (20-60)months). Patients were also divided into inflamed c-reactive protein (CRP >5.6 mg/mL) and non-inflamed. Antibody levels were measured by ELISA. In multivariate risk analysis, patients in low tertile of IgM anti-MDA sub-distribution hazard ratio (sHR 0.54); 95% confidence interval (CI: 0.34-0.89) inversely and significantly associated with all-cause mortality after five years, after adjusting for confounders. Low tertile of IgG (sHR 0.48, 95%CI: 0.25-0.90, = 0.02) and IgG1 (sHR 0.50, CI: 0.24-1.04, = 0.06) was associated low mortality among non-inflamed patients. In contrast, anti-MDA IgG2 among inflamed patients was significantly associated with increased mortality, IgG2(sHR 2.33, CI: 1.16-4.68, = 0.01). IgM anti-MDA was a novel biomarker among HD-patients with low levels being associated with mortality, while low levels of IgG and IgG1 but not IgA anti-MDA were associated with mortality only among non-inflamed patients. IgG2 anti-MDA was a significant risk marker among inflamed patients, which could be related to infection.
接受血液透析的患者（血液透析患者）过早死亡的风险增加。抗丙二醛IgM抗体（抗MDA）水平低与心血管疾病（CVD）风险增加相关，且潜在机制已被描述。在此，我们以死亡率为结局指标，研究了210例血液透析患者的抗MDA亚类和同种型（56%为男性，中位年龄66岁，四分位间距（IQR）为51 - 74岁，透析时间29（15 - 58）个月，平均随访期41（20 - 60）个月）。患者还被分为炎症状态下C反应蛋白（CRP>5.6 mg/mL）组和非炎症组。通过酶联免疫吸附测定法测量抗体水平。在多变量风险分析中，IgM抗MDA亚分布处于低三分位数的患者（风险比（sHR）0.54；95%置信区间（CI：0.34 - 0.89））在调整混杂因素后，与五年后的全因死亡率呈显著负相关。IgG处于低三分位数（sHR 0.48，95%CI：0.25 - 0.90，P = 0.02）和IgG1（sHR 0.50，CI：0.24 - 1.04，P = 0.06）与非炎症患者的低死亡率相关。相比之下，炎症患者中的抗MDA IgG2与死亡率增加显著相关，IgG2（sHR 2.33，CI：1.16 - 4.68，P = 0.01）。IgM抗MDA是血液透析患者中的一种新型生物标志物，其低水平与死亡率相关，而低水平的IgG和IgG1抗MDA但不是IgA抗MDA仅在非炎症患者中与死亡率相关。IgG2抗MDA是炎症患者中的一个显著风险标志物，这可能与感染有关。
