Deriš Helena, Kifer Domagoj, Cindrić Ana, Petrović Tea, Cvetko Ana, Trbojević-Akmačić Irena, Kolčić Ivana, Polašek Ozren, Newson Louise, Spector Tim, Menni Cristina, Lauc Gordan
Genos Glycoscience Research Laboratory, Zagreb 10000, Croatia.
Faculty of Pharmacy and Biochemistry, University of Zagreb, Zagreb 10000, Croatia.
iScience. 2022 Feb 10;25(3):103897. doi: 10.1016/j.isci.2022.103897. eCollection 2022 Mar 18.
Gonadal hormones affect immunoglobulin G (IgG) glycosylation, and the more proinflammatory IgG glycome composition might be one of the molecular mechanisms behind the increased proinflammatory phenotype in perimenopause. Using ultra-high-performance liquid chromatography, we analyzed IgG glycome composition in 5,080 samples from 1940 pre-, peri-, and postmenopausal women. Statistically significant decrease in galactosylation and sialylation was observed in postmenopausal women. Furthermore, during the transition from pre- to postmenopausal period, the rate of increase in agalactosylated structures (0.051/yr; 95%CI = 0.043-0.059, p < 0.001) and decrease in digalactosylated (-0.043/yr; 95%CI = -0.050 to -0.037, p < 0.001) and monosialylated glycans (-0.029/yr; 95%CI = -0.034 to -0.024, p < 0.001) were significantly higher than in either pre- or postmenopausal periods. The conversion to the more proinflammatory IgG glycome and the resulting decrease in the ability of IgG to suppress low-grade chronic inflammation may be an important molecular mechanism mediating the increased health risk in perimenopause and postmenopause.
性腺激素会影响免疫球蛋白G(IgG)的糖基化,而更具促炎作用的IgG糖组构成可能是围绝经期促炎表型增加背后的分子机制之一。我们使用超高效液相色谱法分析了1940名绝经前、围绝经期和绝经后女性的5080份样本中的IgG糖组构成。绝经后女性的半乳糖基化和唾液酸化水平出现了具有统计学意义的下降。此外,在从绝经前到绝经后的过渡期间,去半乳糖基化结构的增加速率(0.051/年;95%置信区间=0.043-0.059,p<0.001)以及双半乳糖基化(-0.043/年;95%置信区间=-0.050至-0.037,p<0.001)和单唾液酸化聚糖(-0.029/年;95%置信区间=-0.034至-0.024,p<0.001)的下降速率显著高于绝经前或绝经后时期。向更具促炎作用的IgG糖组的转变以及由此导致的IgG抑制低度慢性炎症能力的下降,可能是介导围绝经期和绝经后健康风险增加的重要分子机制。