Catera Mariangela, Borelli Vincenzo, Malagolini Nadia, Chiricolo Mariella, Venturi Giulia, Reis Celso A, Osorio Hugo, Abruzzo Provvidenza M, Capri Miriam, Monti Daniela, Ostan Rita, Franceschi Claudio, Dall'Olio Fabio
Dipartimento di Medicina Specialistica Diagnostica e Sperimentale (DIMES) University of Bologna, Bologna, Italy.
Instituto de Investigação e Inovação em Saúde (Institute for Research and Innovation in Health), University of Porto, and Institute of Molecular Pathology and Immunology of The University of Porto IPATIMUP), Porto, Portugal.
Oncotarget. 2016 Feb 16;7(7):7455-68. doi: 10.18632/oncotarget.7059.
The pro- or anti-inflammatory activities of immunoglobulins G (IgGs) are controlled by the structure of the glycan N-linked to Asn297 of their heavy chain. The age-associated low grade inflammation (inflammaging) is associated with increased plasmatic levels of agalactosylated IgGs terminating with N-acetylglucosamine (IgG-G0) whose biogenesis has not been fully explained. Although the biosynthesis of glycans is in general mediated by glycosyltransferases associated with internal cell membranes, the extracellular glycosylation of circulating glycoproteins mediated by plasmatic glycosyltransferases has been recently demonstrated. In this study we have investigated the relationship between plasmatic glycosyltransferases, IgG glycosylation and inflammatory and aging markers. In cohorts of individuals ranging from infancy to centenarians we determined the activity of plasmatic β4 galactosyltransferase(s) (B4GALTs) and of α2,6-sialyltransferase ST6GAL1, the glycosylation of IgG, the GlycoAge test (a glycosylation-based marker of aging) and the plasma level of inflammatory and liver damage markers. Our results show that: 1) plasmatic B4GALTs activity is a new marker of aging, showing a linear increase throughout the whole age range. 2) plasmatic ST6GAL1 was high only in children and in people above 80, showing a quadratic relationship with age. 3) Neither plasmatic glycosyltransferase correlated with markers of liver damage. 4) plasmatic ST6GAL1 showed a positive association with acute phase proteins in offspring of short lived parents, but not in centenarians or in their offspring. 5) Although the glycosylation of IgGs was not correlated with the level of the two plasmatic glycosyltransferases, it showed progressive age-associated changes consistent with a shift toward a pro-inflammatory glycotype.
免疫球蛋白G（IgG）的促炎或抗炎活性受其重链Asn297位点N-糖链结构的控制。与年龄相关的低度炎症（炎症衰老）与血浆中以N-乙酰葡糖胺结尾的无半乳糖IgG（IgG-G0）水平升高有关，其生物合成尚未完全阐明。虽然聚糖的生物合成通常由与细胞内膜相关的糖基转移酶介导，但最近已证明血浆糖基转移酶可介导循环糖蛋白的细胞外糖基化。在本研究中，我们调查了血浆糖基转移酶、IgG糖基化与炎症和衰老标志物之间的关系。在从婴儿到百岁老人的个体队列中，我们测定了血浆β4半乳糖基转移酶（B4GALTs）和α2,6-唾液酸转移酶ST6GAL1的活性、IgG的糖基化、糖龄测试（一种基于糖基化的衰老标志物）以及炎症和肝损伤标志物的血浆水平。我们的结果表明：1）血浆B4GALTs活性是一种新的衰老标志物，在整个年龄范围内呈线性增加。2）血浆ST6GAL1仅在儿童和80岁以上人群中较高，与年龄呈二次关系。3）两种血浆糖基转移酶均与肝损伤标志物无关。4）在短寿父母的后代中，血浆ST6GAL1与急性期蛋白呈正相关，但在百岁老人及其后代中并非如此。5）虽然IgG的糖基化与两种血浆糖基转移酶的水平无关，但它显示出与年龄相关的渐进性变化，与向促炎糖型的转变一致。
