Knip Mikael, Siljander Heli, Ilonen Jorma, Simell Olli, Veijola Riitta
Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland.
Pediatr Diabetes. 2016 Jul;17 Suppl 22:17-24. doi: 10.1111/pedi.12386.
Islet cell antibodies (ICA) were found for the first time more than 40 yr ago in patients with autoimmune endocrine deficiencies, including type 1 diabetes (T1D). ICA detected by indirect immunofluorescence represent a heterogeneous group of autoantibodies targeting a series of biochemical autoantigens, such as the protein tyrosine phosphatase related islet antigen 2 (IA-2), the 65 kD isoform of glutamic acid decarboxylase (GA65), and zinc transporter 8 (ZnT8) as well as currently unidentified autoantigens. The general view is that the diabetes-associated autoantibodies are not directly involved in beta-cell destruction but function as biomarkers of an ongoing destructive process. The diabetes-associated autoantibodies remain the strongest predictive marker for future development of T1D. Positivity for multiple (≥2) autoantibodies is highly predictive of clinical disease both among first-degree relatives and in the general population. Autoantibody titers are highly variable during the preclinical phase, but in many cases the titers tend to decrease before diagnosis. The first signs of beta-cell autoimmunity may appear early during the first months of life. The majority of those individuals diagnosed with T1D before puberty seroconvert to autoantibody positivity before the age of 3 yr. The natural course and duration of preclinical diabetes vary substantially from one individual to another. The characteristics of the isotype-specific response during preclinical diabetes appear to be antigen-specific. Diabetes-associated autoantibodies may be useful surrogate markers of the subsequent development of T1D in primary prevention trials. T1D may occur, albeit rarely, in the absence of any signs of humoral autoimmunity at diagnosis.
40多年前，人们首次在患有自身免疫性内分泌缺陷的患者中发现胰岛细胞抗体（ICA），其中包括1型糖尿病（T1D）患者。通过间接免疫荧光检测到的ICA代表了一组异质性自身抗体，它们靶向一系列生化自身抗原，如蛋白酪氨酸磷酸酶相关胰岛抗原2（IA-2）、谷氨酸脱羧酶65kD亚型（GA65）、锌转运体8（ZnT8）以及目前尚未确定的自身抗原。一般观点认为，与糖尿病相关的自身抗体并不直接参与β细胞的破坏，而是作为正在进行的破坏过程的生物标志物。与糖尿病相关的自身抗体仍然是T1D未来发展的最强预测标志物。在一级亲属和普通人群中，多种（≥2种）自身抗体呈阳性对临床疾病具有高度预测性。在临床前期，自身抗体滴度变化很大，但在许多情况下，滴度在诊断前往往会下降。β细胞自身免疫的最初迹象可能在生命的头几个月就出现。大多数在青春期前被诊断为T1D的个体在3岁前血清转化为自身抗体阳性。临床前期糖尿病的自然病程和持续时间因人而异。临床前期糖尿病期间同种型特异性反应的特征似乎具有抗原特异性。在一级预防试验中，与糖尿病相关的自身抗体可能是T1D后续发展的有用替代标志物。在诊断时，T1D可能会在没有任何体液自身免疫迹象的情况下发生，尽管这种情况很少见。
