Nemčić Matej, Shkunnikova Sofia, Kifer Domagoj, Plavša Branimir, Vučić Lovrenčić Marijana, Morahan Grant, Duvnjak Lea, Pociot Flemming, Gornik Olga
Department of Biochemistry and Molecular Biology, Faculty of Pharmacy and Biochemistry, Ante Kovačića 1, Zagreb, Croatia.
Department of Biophysics, Faculty of Pharmacy and Biochemistry, Ante Kovačića 1, Zagreb, Croatia.
Heliyon. 2024 May 3;10(9):e30529. doi: 10.1016/j.heliyon.2024.e30529. eCollection 2024 May 15.
To identify N-glycan structures on immunoglobulin A related to type 1 diabetes mellitus among children at the disease onset and adults with type 1 diabetes mellitus.
Human polyclonal IgA N-glycans were profiled using hydrophilic interaction ultra performance liquid chromatography in two cohorts. The first cohort consisted of 62 children at the onset of type 1 diabetes mellitus and 86 of their healthy siblings. The second cohort contained 84 adults with the disease and 84 controls. Associations between N-glycans and type 1 diabetes mellitus were tested using linear mixed model for the paediatric cohort, or general linear model for the adult cohort. False discovery rate was controlled by Benjamini-Hochberg method modified by Li and Ji.
In children, an increase in a single oligomannose N-glycan was associated with type 1 diabetes mellitus (B = 0.529, p = 0.0067). N-glycome of the adults displayed increased branching (B = 0.466, p = 0.0052), trigalactosylation (B = 0.466, p = 0.0052), trisialylation (B = 0.629, p < 0.001), and mannosylation (B = 0.604, p < 0.001). The strongest association with the disease was a decrease in immunoglobulin A core fucosylation (B = -0.900, p < 0.001).
Changes in immunoglobulin N-glycosylation patterns in type 1 diabetes point to disruptions in immunoglobulin A catabolism and dysregulated inflammatory capabilities of the antibody, potentially impacting immune responses and inflammation.
识别疾病发作期儿童及成年1型糖尿病患者中与1型糖尿病相关的免疫球蛋白A上的N - 聚糖结构。
在两个队列中使用亲水相互作用超高效液相色谱法对人多克隆IgA N - 聚糖进行分析。第一个队列由62名1型糖尿病发作期儿童及其86名健康同胞组成。第二个队列包含84名成年患者和84名对照。使用线性混合模型对儿科队列或成年队列的一般线性模型测试N - 聚糖与1型糖尿病之间的关联。错误发现率通过Li和Ji修改的Benjamini - Hochberg方法进行控制。
在儿童中，单一低聚甘露糖N - 聚糖的增加与1型糖尿病相关（B = 0.529，p = 0.0067）。成年患者的N - 聚糖组显示分支增加（B = 0.466，p = 0.0052）、三半乳糖基化增加（B = 0.466，p = 0.0052）、三唾液酸化增加（B = 0.629，p < 0.001）和甘露糖基化增加（B = 0.604，p < 0.001）。与该疾病最强的关联是免疫球蛋白A核心岩藻糖基化减少（B = -0.900，p < 0.001）。
1型糖尿病中免疫球蛋白N - 糖基化模式的变化表明免疫球蛋白A分解代谢的破坏以及抗体炎症调节能力失调，可能影响免疫反应和炎症。
