Supplementary Material for: Should the Negativity for Islet Cell Autoantibodies Be Used in a Prescreening for Genetic Testing in Maturity-Onset Diabetes of the Young? The Case of Autoimmunity-Associated Destruction of Pancreatic β-Cells in a Family of HNF1A-MODY Subjects

It was recently suggested that routine islet cell autoantibody testing should be performed to discriminate maturity-onset diabetes of the young (MODY) from type 1 diabetes mellitus (T1DM). This is the first report ever to describe the familial manifestation of T1DM autoimmunity in nonobese HNF1A-MODY subjects and the presence of islet antigen-2 (IA-2) antibodies in MODY subjects. Three nonobese subjects in an age range of 14-35 years were diagnosed with HNF1A-MODY (p. Arg159Gln mutation). All the tested subjects had detectable (but varying) levels of islet cell autoantibodies (i.e., antibodies against glutamate decarboxylase or IA-2) in the absence of other T1DM characteristics. They displayed long-term expression of intermediate fasting C-peptide levels, ketoacidosis was absent even in periods of spontaneous insulin withdrawal, and full dependence on externally administered insulin was not detected in any of them although better glycemic control was achieved when insulin was supplemented. The course of the disease was similar to that of the autoantibody-negative HNF1A-MODY subjects. The case questions the selectivity of autoantibodies as a marker of T1DM or late-onset autoimmune diabetes of adulthood (LADA) over MODY and challenges the use of autoantibodies as a universal negative marker of MODY in an effort to decrease the cost of health care, as it may eventually lead to the wrong diagnosis and thus to the incorrect treatment. Further research should involve examination of the autoantibody titers and prevalence in large and geographically diverse cohorts of MODY subjects selected for genetic testing (regardless of their autoantibody titers) as well as determination of the islet cell autoantibody kinetics in the course of MODY onset and progression.

近期有研究建议，应常规开展胰岛细胞自身抗体检测，以鉴别青少年起病的成年型糖尿病（maturity-onset diabetes of the young, MODY）与1型糖尿病（type 1 diabetes mellitus, T1DM）。此为首篇报道，描述了非肥胖型HNF1A-MODY受试者中T1DM自身免疫的家族性表现，以及MODY受试者体内胰岛抗原2（islet antigen-2, IA-2）抗体的存在情况。
本研究纳入3名年龄介于14~35岁的非肥胖受试者，均被诊断为携带p.Arg159Gln突变的HNF1A-MODY。所有受检受试者均检出水平各异的胰岛细胞自身抗体（即针对谷氨酸脱羧酶或IA-2的抗体），但未表现出其他T1DM特征。受试者长期维持中等水平的空腹C肽，即使在自发停用胰岛素的时段也未出现酮症酸中毒；尽管补充胰岛素可更好地控制血糖，但所有受试者均未出现完全依赖外源性胰岛素的情况。该疾病的病程与自身抗体阴性的HNF1A-MODY受试者一致。
本案例对"自身抗体可作为区分T1DM或成人隐匿性自身免疫糖尿病（late-onset autoimmune diabetes of adulthood, LADA）与MODY的特异性标志物"这一观点提出质疑，同时挑战了"将自身抗体作为MODY通用阴性标志物以降低医疗成本"的做法——因为此类做法最终可能导致误诊及不当治疗。
未来研究应涵盖：对经基因检测筛选的、规模庞大且地理分布广泛的MODY受试者队列（无论其自身抗体滴度如何）检测自身抗体滴度与患病率；同时明确MODY发病及进展过程中的胰岛细胞自身抗体动力学变化。