title: Case report: type 1 diabetes in monozygotic quadruplets.
abstract: 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-α 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.
authors: Department of Paediatrics, 2nd Medical Faculty of Charles University and University Hospital Motol, Prague, Czech Republic. katerina.stechova@lfmotol.cuni.cz
authors: Katerina
authors: K
authors: Stechova
authors: Zbynek
authors: Z
authors: Halbhuber
authors: Miluse
authors: M
authors: Hubackova
authors: Jana
authors: J
authors: Kayserova
authors: Lenka
authors: L
authors: Petruzelkova
authors: Jana
authors: J
authors: Vcelakova
authors: Stanislava
authors: S
authors: Kolouskova
authors: Tereza
authors: T
authors: Ulmannova
authors: Maria
authors: M
authors: Faresjö
authors: Ales
authors: A
authors: Neuwirth
authors: Radek
authors: R
authors: Spisek
authors: Anna
authors: A
authors: Sediva
authors: Dominik
authors: D
authors: Filipp
authors: Zdenek
authors: Z
authors: Sumnik
mesh_terms: D015551:Autoimmunity; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology*; D005260:Female; D006801:Humans; D011783:Quadruplets; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism