Univ Lille, CHU Lille, Laboratoire de virologie ULR3610 F-59000 Lille, France.
Department of Virology, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
Diabetes Metab Res Rev. 2020 Sep;36(6):e3305. doi: 10.1002/dmrr.3305. Epub 2020 Mar 25.
Studies in prospective cohorts have suggested that enterovirus infections are associated with the appearance of islet autoantibodies that precede later appearance of type 1 diabetes (T1D). It was shown that in addition to an antibody-mediated anti-coxsackievirus (CV)-B neutralizing activity of serum from patients with T1D, there was also enhancing anti-CV-B activity in vitro. In this study, the patterns of enhancing and neutralizing anti-CV activities were analysed from consecutive serum samples collected from children who were followed from birth until they developed T1D in the Finnish Type 1 Diabetes Prediction and Prevention (DIPP) study and compared to those in non-diabetic control children.
The titres of serum neutralizing activity were analysed against those CVs which were detected in the stools in these children (CV-B3, CV-B5 or CV-A4) using plaque assay. The enhancing activity of these serum samples was analysed by measuring interferon-alpha (INF-α) production in cultures of peripheral blood mononuclear cells (PBMC) inoculated with a mixture of these viruses and diluted serum.
A sustained anti-CV enhancing activity was observed in consecutive serum samples in patients with T1D. The pattern of responses differed between children who developed T1D and control children. In patients, the anti-CV enhancing activity was predominant or even exclusive over the neutralizing activity, whereas in controls the enhancing and neutralising activities were more balanced or the neutralizing activity was largely predominant.
Evaluating the anti-enterovirus neutralizing and enhancing activity of serum samples can be useful to investigate further the relationship between enteroviruses and the development of T1D.
前瞻性队列研究表明，肠道病毒感染与胰岛自身抗体的出现有关，而后者先于 1 型糖尿病（T1D）的出现。研究表明，除了 T1D 患者血清中存在抗体介导的抗柯萨奇病毒（CV）-B 中和活性外，体外还存在增强的抗 CV-B 活性。在这项研究中，分析了来自芬兰 1 型糖尿病预测和预防（DIPP）研究中连续采集的血清样本中的增强和中和抗 CV 活性模式，这些儿童从出生开始随访，直到他们在研究中发展为 T1D，并将其与非糖尿病对照儿童进行了比较。
使用斑块测定法分析血清中和活性针对这些在这些儿童粪便中检测到的 CV（CV-B3、CV-B5 或 CV-A4）的效价。通过测量接种这些病毒混合物和稀释血清的外周血单核细胞（PBMC）培养物中干扰素-α（INF-α）的产生来分析这些血清样本的增强活性。
在 T1D 患者的连续血清样本中观察到持续的抗 CV 增强活性。在发生 T1D 和对照组儿童之间，反应模式不同。在患者中，抗 CV 增强活性占主导地位，甚至是中和活性的唯一形式，而在对照组中，增强和中和活性更平衡，或中和活性占主导地位。
评估血清样本的抗肠道病毒中和和增强活性有助于进一步研究肠道病毒与 T1D 发展之间的关系。
