Frostegård Johan, Su Jun, Sing Sudhir, Hua Xiang, Vikström Max, Leander Karin, Gigante Bruna, de Faire Ulf, Frostegård Anna G
Unit of Immunology and Chronic Disease, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Department of Emergency Medicine, Karolinska University Hospital, Stockholm, Sweden.
PLoS One. 2017 Apr 21;12(4):e0171195. doi: 10.1371/journal.pone.0171195. eCollection 2017.
Phosphatidylserine is exposed on apoptotic cells and is prone to oxidation (OxPS). Here we analyze the association of IgM antibodies against OxPS (anti-OxPS) with the risk of cardiovascular disease (CVD).
Among sixty-year olds from Stockholm County in Sweden, previously screened for cardiovascular risk factors (2039 men, 2193 women), there were 210 incident CVD-cases identified during a 5-year follow-up. Using a nested case-control design, 622 age- and sex-matched controls were selected. Odds ratios (OR) with 95% intervals (CI) were calculated by conditional logistic regression. IgM anti-OxPS was measured by ELISA. Phagocytosis of apoptotic Jurkat-cells by macrophages was studied by flow cytometry.
Anti-OxPS levels were lower among cases (median (interquartile range): 80.7 (60.9-101.0 vs. 84.6 (65.8-109.6); p = 0.047); among men (76.6 (55.8-99.2) vs. 82.0 (63.1-105.1); p = 0.022) and among women 89.6 (72.3-110.1) vs. 89.8 (69.9-114.4); p = 0.79). After adjustment for smoking, BMI, diabetes mellitus type II, hypercholesterolaemia and hypertension, and dividing into quartiles, using the highest quartile (quartile 4) as reference, quartile 3 was associated with a OR of 1.74 (CI 1.08-2.81). Quartiles 2 and 1 had similar associations, the later reaching statistical significance. Among men associations were stronger whereas no significant associations were observed in women. The OR of MI/angina comparing quartile 3 with quartile 4 was 2.31 (CI 1.30-4.11). The OR for quartile 2 and 1, respectively, were similar as for quartile 3. Total IgM increased uptake of apoptotic cells, which was reversed if incubated with OxPS.
IgM anti-OxPS is a novel potential protection marker for CVD, in particular in men. Increased phagocytosis of dying/dead cells could be one potential underlying mechanism.
磷脂酰丝氨酸暴露于凋亡细胞表面且易于氧化（氧化磷脂酰丝氨酸，OxPS）。在此，我们分析抗氧化磷脂酰丝氨酸IgM抗体（抗OxPS）与心血管疾病（CVD）风险之间的关联。
在瑞典斯德哥尔摩县先前已筛查心血管危险因素的60岁人群中（2039名男性，2193名女性），在5年随访期间确定了210例CVD新发病例。采用巢式病例对照设计，选取622名年龄和性别匹配的对照。通过条件逻辑回归计算比值比（OR）及95%可信区间（CI）。采用酶联免疫吸附测定法检测抗OxPS IgM。通过流式细胞术研究巨噬细胞对凋亡Jurkat细胞的吞噬作用。
病例组的抗OxPS水平较低（中位数（四分位间距）：80.7（60.9 - 101.0）对84.6（65.8 - 109.6）；p = 0.047）；男性中（76.6（55.8 - 99.2）对82.0（63.1 - 105.1）；p = 0.022），女性中（89.6（72.3 - 110.1）对89.8（69.9 - 114.4）；p = 0.79）。在对吸烟、体重指数、II型糖尿病、高胆固醇血症和高血压进行校正后，并分为四分位数，以最高四分位数（四分位数4）为参照，四分位数3的OR为1.74（CI 1.08 - 2.81）。四分位数2和1有相似的关联，后者达到统计学显著性。男性中的关联更强，而女性中未观察到显著关联。将四分位数3与四分位数4比较，心肌梗死/心绞痛的OR为2.31（CI 1.30 - 4.11）。四分位数2和1的OR分别与四分位数3相似。总IgM增加凋亡细胞摄取，若与OxPS一起孵育则这种作用逆转。
抗OxPS IgM是CVD一种新的潜在保护标志物，尤其在男性中。死亡/濒死细胞吞噬作用增加可能是一种潜在的机制。
