Department of Paediatric Infectious Diseases and Immunology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands.
Sanquin Research and Landsteiner Laboratory, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Aging Cell. 2024 Jul;23(7):e14167. doi: 10.1111/acel.14167. Epub 2024 Apr 15.
Down syndrome (DS) is characterized by lowered immune competence and premature aging. We previously showed decreased antibody response following SARS-CoV-2 vaccination in adults with DS. IgG1 Fc glycosylation patterns are known to affect the effector function of IgG and are associated with aging. Here, we compare total and anti-spike (S) IgG1 glycosylation patterns following SARS-CoV-2 vaccination in DS and healthy controls (HC). Total and anti-Spike IgG1 Fc N-glycan glycoprofiles were measured in non-exposed adults with DS and controls before and after SARS-CoV-2 vaccination by liquid chromatography-mass spectrometry (LC-MS) of Fc glycopeptides. We recruited N = 44 patients and N = 40 controls. We confirmed IgG glycosylation patterns associated with aging in HC and showed premature aging in DS. In DS, we found decreased galactosylation (50.2% vs. 59.0%) and sialylation (6.7% vs. 8.5%) as well as increased fucosylation (97.0% vs. 94.6%) of total IgG. Both cohorts showed similar bisecting GlcNAc of total and anti-S IgG1 with age. In contrast, anti-S IgG1 of DS and HC showed highly comparable glycosylation profiles 28 days post vaccination. The IgG1 glycoprofile in DS exhibits strong premature aging. The combination of an early decrease in IgG1 Fc galactosylation and sialylation and increase in fucosylation is predicted to reduce complement activity and decrease FcγRIII binding and subsequent activation, respectively. The altered glycosylation patterns, combined with decreased antibody concentrations, help us understand the susceptibility to severe infections in DS. The effect of premature aging highlights the need for individuals with DS to receive tailored vaccines and/or vaccination schedules.
唐氏综合征（DS）的特征是免疫能力降低和早衰。我们之前曾表明，DS 成人在接种 SARS-CoV-2 疫苗后抗体反应下降。IgG1 Fc 糖基化模式已知会影响 IgG 的效应功能，并与衰老有关。在这里，我们比较了 DS 和健康对照组（HC）接种 SARS-CoV-2 后的总抗体和抗刺突（S）IgG1 糖基化模式。通过液相色谱-质谱（LC-MS）对 Fc 糖肽进行分析，在未暴露的 DS 和对照组成人中测量了接种 SARS-CoV-2 前后的总抗体和抗-Spike IgG1 Fc N-糖基化糖型谱。我们招募了 N=44 例患者和 N=40 例对照。我们证实了 HC 中与衰老相关的 IgG 糖基化模式，并显示 DS 存在早衰。在 DS 中，我们发现总 IgG 的半乳糖基化（50.2%比 59.0%）和唾液酸化（6.7%比 8.5%）减少，而岩藻糖基化（97.0%比 94.6%）增加。两个队列的总 IgG 和抗-S IgG1 的双叉 GlcNAc 都随年龄而增加。相比之下，接种后 28 天，DS 和 HC 的抗-S IgG1 表现出非常相似的糖基化模式。DS 的 IgG1 糖型谱表现出强烈的早衰。IgG1 Fc 半乳糖基化和唾液酸化早期减少以及岩藻糖基化增加的组合预计会分别降低补体活性，减少 FcγRIII 结合和随后的激活。改变的糖基化模式，加上抗体浓度降低，有助于我们了解 DS 中严重感染的易感性。早衰的影响突出了 DS 个体需要接受量身定制的疫苗和/或接种时间表。
