Fiskesund Roland, Su Jun, Bulatovic Ivana, Vikström Max, de Faire Ulf, Frostegård Johan
Institute of Environmental Medicine, Unit of Immunology and Chronic Disease, Karolinska Institutet, Stockholm, Sweden.
Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
Results Immunol. 2012 Jan 8;2:13-8. doi: 10.1016/j.rinim.2012.01.001. eCollection 2012.
We have reported that anti-phosphorylcholine (anti-PC) IgM is a protection marker for human cardiovascular disease (CVD) and atherosclerosis. We here investigate the anti-PC autoantibodies in a well-defined cohort with regard to idiotype, atherosclerosis progression and mechanisms for its protective action.
Serum levels and binding specificities of different anti-PC isotypes were determined in 226 hypertensive individuals enrolled in European Lacidipine Study on Atherosclerosis using ELISA. The mean of the maximum Intima-Media Thicknesses (IMT) in the far walls of common carotids and bifurcations was assessed at the time of inclusion, and four years afterwards. Apoptosis in immune cells was induced with lysophosphatidylcholine (LPC) and quantified using the MTT-assay.
Anti-PC IgM, IgA and IgG1 (but not IgG2) was negatively associated with IMT-progression. Combining anti-PC IgM with data on antibodies against oxidized- and malondialdehyde-modified LDL further strengthened this association. At very high levels, anti-PC IgM exhibited a striking negative association with atherosclerosis progression (OR 0.05; CI 0.006-0.40). Analysis of serum samples taken four years apart in study participants affirmed the stability of anti-PC IgM titers over time. Examination of fine specificities revealed that the protective isotypes (IgM, IgA and IgG1) are of the Group I idiotype whereas the non-protective IgG2 subclass was Group II. Anti-PC IgM inhibited LPC-induced cell death of immune cells.
Group I anti-PC antibodies, particularly of the IgM class, are independent protection markers for atherosclerosis progression. One potential mechanism of action is inhibition of LPC-induced cell cytotoxicity.
我们曾报道抗磷酸胆碱（anti-PC）IgM是人类心血管疾病（CVD）和动脉粥样硬化的一种保护标志物。我们在此研究一个明确队列中的抗PC自身抗体，涉及独特型、动脉粥样硬化进展及其保护作用机制。
使用ELISA法测定了参与欧洲拉西地平动脉粥样硬化研究的226名高血压个体中不同抗PC同种型的血清水平和结合特异性。在纳入研究时及四年后，评估了颈总动脉远壁和分叉处内膜中层厚度（IMT）最大值的平均值。用溶血磷脂酰胆碱（LPC）诱导免疫细胞凋亡，并使用MTT法进行定量。
抗PC IgM、IgA和IgG1（而非IgG2）与IMT进展呈负相关。将抗PC IgM与抗氧化型和丙二醛修饰型LDL抗体的数据相结合，进一步加强了这种关联。在非常高的水平时，抗PC IgM与动脉粥样硬化进展呈现显著的负相关（OR 0.05；CI 0.006 - 0.40）。对研究参与者相隔四年采集的血清样本进行分析，证实了抗PC IgM滴度随时间的稳定性。对精细特异性的检查显示，保护性同种型（IgM、IgA和IgG1）属于I组独特型，而非保护性IgG2亚类属于II组。抗PC IgM抑制LPC诱导的免疫细胞死亡。
I组抗PC抗体，尤其是IgM类，是动脉粥样硬化进展的独立保护标志物。一种潜在的作用机制是抑制LPC诱导的细胞毒性。
