Thorsen S U, Pipper C B, Johannesen J, Mortensen H B, Pociot F, Svensson J
Copenhagen Diabetes Research Center (CPH-DIRECT), Department of Paediatrics, Herlev Hospital, University of Copenhagen, Herlev, Denmark.
Department of Public Health, Section of Biostatistics, University of Copenhagen, Copenhagen K, Denmark.
Scand J Immunol. 2018 Jan;87(1):46-53. doi: 10.1111/sji.12632. Epub 2017 Dec 12.
B cells have recently entered the stage as an important accessory player in type 1 diabetes (T1D) etiopathogenesis. Experimental studies suggest regulatory functions of vitamin D on B cells. However, only a few human studies, with considerable methodological limitations, have been conducted within this field. Our objective was to investigate whether higher 25-hydroxyvitamin D (25(OH)D) concentrations were inversely associated with β-cell autoantigens glutamic acid decarboxylase (isoform 65) (GADA) and insulinoma-associated antigen-2A (IA-2A). Further, we also wanted to examine the relationship between 25(OH)D and total antibody concentrations. We randomly selected 500 patients with newly diagnosed T1D and 500 siblings for 25(OH)D, antibody and genetic analysis from the population-based Danish Registry of Childhood and Adolescent Diabetes. The relative change (RC) in the mean concentration of GADA, IA-2A and antibody isotypes by a 10 nmol/l increase in 25(OH)D concentration was modelled by a robust log-normal regression model. We found no association between 25(OH)D and GADA [adjusted RC per 10 nmol/l increase: 1.00; 95% confidence interval (CI): 0.98-1.02] and IA-2A [adjusted RC per 10 nmol/l increase: 0.92; CI: 0.76-1.12]. Further, 25(OH)D was not associated with the total concentration of antibody isotypes [immunoglobulin (Ig)A, IgE, IgG and IgM]. All null findings were unaltered after adjustment for genetic variation in the vitamin D pathway. Physiological concentrations of 25(OH)D are unlikely to have a clinically important effect on antibody concentrations in a paediatric population of newly diagnosed patients with T1D and their healthy siblings.
B细胞最近作为1型糖尿病（T1D）发病机制中的一个重要辅助角色进入了研究阶段。实验研究表明维生素D对B细胞具有调节功能。然而，该领域内仅开展了少数人体研究，且存在相当大的方法学局限性。我们的目的是调查较高的25-羟基维生素D（25(OH)D）浓度是否与β细胞自身抗原谷氨酸脱羧酶（异构体65）（GADA）和胰岛瘤相关抗原2A（IA-2A）呈负相关。此外，我们还想研究25(OH)D与总抗体浓度之间的关系。我们从基于人群的丹麦儿童和青少年糖尿病登记处随机选取了500例新诊断的T1D患者和500名同胞进行25(OH)D、抗体和基因分析。通过稳健的对数正态回归模型模拟了25(OH)D浓度每增加10 nmol/l时GADA、IA-2A和抗体亚型平均浓度的相对变化（RC）。我们发现25(OH)D与GADA[每增加10 nmol/l调整后的RC：1.00；95%置信区间（CI）：0.98 - 1.02]和IA-2A[每增加10 nmol/l调整后的RC：0.92；CI：0.76 - 1.12]之间无关联。此外，25(OH)D与抗体亚型（免疫球蛋白（Ig）A、IgE、IgG和IgM）的总浓度也无关联。在对维生素D途径中的基因变异进行调整后，所有的阴性结果均未改变。在新诊断的T1D患儿及其健康同胞的儿科人群中，生理浓度的25(OH)D不太可能对抗体浓度产生临床上重要的影响。
