Alnek Kristi, Tagoma Aili, Metsküla Kaja, Talja Ija, Janson Helis, Mandel Maire, Vorobjova Tamara, Oras Astrid, Sepp Hanna, Pruul Katrin, Reimand Koit, Simonen Tiia, Peet Aleksandr, Reppo Ingrid, Tammiksaar Kaia, Lubi Maire, Heilman Kaire, Einberg Ülle, Kisand Kalle, Lember Margus, Tillmann Vallo, Uibo Raivo
Department of Immunology, Institute of Bio- and Translational Medicine, University of Tartu, 50411, Tartu, Estonia.
United Laboratories of Tartu University Hospital, 50406, Tartu, Estonia.
Sci Rep. 2025 May 3;15(1):15491. doi: 10.1038/s41598-025-99664-8.
This study aimed to compare the immunological and immunogenetic profiles over a spectrum of childhood- and adulthood-onset T1D at diagnosis. The cross-sectional study involved participants with recently diagnosed T1D (n = 168), aged 2.9-68.2 years. HLA-II alleles, single nucleotide polymorphisms (SNP) (rs2476601, rs3087243, rs1990760, rs13266634), thyroid and coeliac disease-related autoantibodies and anti-enterovirus antibodies (anti-EV) were analysed regarding the diabetes-associated autoantibodies' (DAA) status and the age of participants. In the longitudinal study, 19 immune checkpoint gene expression levels in children (n = 25) aged 3.6-14.5 years were measured at diagnosis and 1 year after diagnosis. The duration of symptoms before diagnosis was age-dependent. Older age increased the odds of being single DAA-positive (OR 1.05; 95% CI 1.02-1.09), while anti-EV IgG positivity increased the odds of being multiple DAA-positive (adjusted OR 4.42; 95% CI 1.62-12.04). The DAA-negative T1D participants were older than the DAA-positive individuals. The checkpoint gene expression levels between the two time points were similar, but exhibited more pronounced variability at the time of diagnosis. These results confirm immunological variability in recent-onset T1D cases between children and adults and stress the importance of further research to define the comprehensive immunological profile of the disease age-related subgroups.
本研究旨在比较诊断时儿童期和成年期发病的1型糖尿病患者在免疫和免疫遗传特征方面的差异。这项横断面研究纳入了168名最近诊断为1型糖尿病的参与者,年龄在2.9至68.2岁之间。针对糖尿病相关自身抗体(DAA)状态和参与者年龄,分析了人类白细胞抗原II类(HLA-II)等位基因、单核苷酸多态性(SNP)(rs2476601、rs3087243、rs1990760、rs13266634)、甲状腺和乳糜泻相关自身抗体以及抗肠道病毒抗体(抗-EV)。在纵向研究中,测量了3.6至14.5岁儿童(n = 25)在诊断时和诊断后1年的19种免疫检查点基因表达水平。诊断前症状持续时间与年龄有关。年龄较大增加了单一DAA阳性的几率(比值比[OR] 1.05;95%置信区间[CI] 1.02 - 1.09),而抗-EV IgG阳性增加了多种DAA阳性的几率(校正OR 4.42;95% CI 1.62 - 12.04)。DAA阴性的1型糖尿病参与者比DAA阳性个体年龄更大。两个时间点之间的检查点基因表达水平相似,但在诊断时表现出更明显的变异性。这些结果证实了新发病的1型糖尿病儿童和成人病例在免疫方面的变异性,并强调了进一步研究以确定该疾病年龄相关亚组综合免疫特征的重要性。