Case report: type 1 diabetes in monozygotic quadruplets
2012 (English)In: European Journal of Human Genetics, ISSN 1018-4813, E-ISSN 1476-5438, Vol. 20, no 4, 457-462 p.Article in journal (Refereed) Published
Type 1 diabetes (T1D) is an autoimmune disease characterized by the lack of insulin due to an autoimmune destruction of pancreatic beta cells. Here, we report a unique case of a family with naturally conceived quadruplets in which T1D was diagnosed in two quadruplets simultaneously. At the same time, the third quadruplet was diagnosed with the pre-diabetic stage. Remarkably, all four quadruplets were positive for anti-islet cell antibodies, GAD65 and IA-A2. Monozygotic status of the quadruplets was confirmed by testing 14 different short tandem repeat polymorphisms. Serological examination confirmed that all quadruplets and their father suffered from a recent enteroviral infection of EV68-71 serotype. To assess the nature of the molecular pathological processes contributing to the development of diabetes, immunocompetent cells isolated from all family members were characterized by gene expression arrays, immune-cell enumerations and cytokine-production assays. The microarray data provided evidence that viral infection, and IL-27 and IL-9 cytokine signalling contributed to the onset of T1D in two of the quadruplets. The propensity of stimulated immunocompetent cells from non-diabetic members of the family to secrete high level of IFN-alpha further corroborates this conclusion. The number of T regulatory cells as well as plasmacytoid and/or myeloid dendritic cells was found diminished in all family members. Thus, this unique family is a prime example for the support of the so-called fertile-field hypothesis proposing that genetic predisposition to anti-islet autoimmunity is fertilized and precipitated by a viral infection leading to a fully blown T1D.
Place, publisher, year, edition, pages
Nature Publishing Group , 2012. Vol. 20, no 4, 457-462 p.
type 1 diabetes, monozygotic quadruplets, enteroviral infection, gene expression array, cytokine array, genetic predisposition to diabetes
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-76613DOI: 10.1038/ejhg.2011.212ISI: 000301736600015OAI: oai:DiVA.org:liu-76613DiVA: diva2:515452
Funding Agencies|Czech Ministry of Education|NPVII 2B06019|Ministry of Education, Youth and Sports of the Czech Republic|VZ MSM 0021620812|Ministry of Health|MZOFNM2005|project GACR|P302/10/1679|Czech Ministry of Education, Youth and Sports|NPVII 2B08066|Academy of Sciences of the Czech Republic|AVOZ50520514|2012-04-132012-04-132012-04-13