1. Enhancing and neutralizing anti-coxsackievirus activities in serum samples from patients prior to development of type 1 diabetes
- Author
-
Sami Oikarinen, Mikael Knip, Enagnon Kazali Alidjinou, Riitta Veijola, Ilka Engelmann, Amir-Babak Sioofy-Khojine, Jorma Ilonen, Famara Sane, Heikki Hyöty, Antoine Bertin, Didier Hober, Jorma Toppari, HUS Children and Adolescents, Children's Hospital, University of Helsinki, CAMM - Research Program for Clinical and Molecular Metabolism, and Faculty of Medicine
- Subjects
Male ,type 1 diabetes ,Endocrinology, Diabetes and Metabolism ,AUTOIMMUNITY ,enhancing and neutralizing antibodies ,030204 cardiovascular system & hematology ,medicine.disease_cause ,BLOOD MONONUCLEAR-CELLS ,0302 clinical medicine ,Endocrinology ,Child ,Finland ,Virus quantification ,CV-B5 ,biology ,CV-B3 ,enterovirus ,INDUCTION ,in vitro ,Prognosis ,Enterovirus B, Human ,3. Good health ,IFN- α ,Child, Preschool ,Female ,Antibody ,CV-A4 ,Adolescent ,Coxsackievirus Infections ,030209 endocrinology & metabolism ,Coxsackievirus ,Peripheral blood mononuclear cell ,03 medical and health sciences ,Diabetes mellitus ,Internal Medicine ,medicine ,Humans ,B4-INDUCED PRODUCTION ,Autoantibodies ,Type 1 diabetes ,business.industry ,Infant, Newborn ,Autoantibody ,Infant ,IFN-ALPHA ,medicine.disease ,biology.organism_classification ,Antibodies, Neutralizing ,Diabetes Mellitus, Type 1 ,Immunoglobulin G ,3121 General medicine, internal medicine and other clinical medicine ,Immunology ,ANTIBODIES ,Leukocytes, Mononuclear ,biology.protein ,Enterovirus ,3111 Biomedicine ,INTERFERON-ALPHA ,business ,Biomarkers ,B4 ,DEPENDENT ENHANCEMENT ,Follow-Up Studies - Abstract
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 analyzed 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 titers of serum neutralizing activity were analyzed 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 neutralizing activities were more balanced or the neutralizing activity was largely predominant. In conclusion, 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. This article is protected by copyright. All rights reserved.
- Published
- 2020