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Prospective virome analyses in young children at increased genetic risk for type 1 diabetes

Vehik, Kendra ; Lynch, Kristian F ; Wong, Matthew C ; Tian, Xiangjun ; Ross, Matthew C ; Gibbs, Richard A ; Ajami, Nadim J ; Petrosino, Joseph F ; Rewers, Marian ; Toppari, Jorma ; Ziegler, Anette G ; She, Jin-Xiong ; Lernmark, Ake ; Akolkar, Beena ; Hagopian, William A ; Schatz, Desmond A ; Krischer, Jeffrey P ; Hyöty, Heikki ; Lloyd, Richard E

Nature medicine, 2019-12, Vol.25 (12), p.1865-1872 [Revista revisada por pares]

United States: Nature Publishing Group

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Prospective virome analyses in young children at increased genetic risk for type 1 diabetes
Autor: Vehik, Kendra ; Lynch, Kristian F ; Wong, Matthew C ; Tian, Xiangjun ; Ross, Matthew C ; Gibbs, Richard A ; Ajami, Nadim J ; Petrosino, Joseph F ; Rewers, Marian ; Toppari, Jorma ; Ziegler, Anette G ; She, Jin-Xiong ; Lernmark, Ake ; Akolkar, Beena ; Hagopian, William A ; Schatz, Desmond A ; Krischer, Jeffrey P ; Hyöty, Heikki ; Lloyd, Richard E
Materias: Adolescent ; Autoimmunity ; Autoimmunity - genetics ; Autoimmunity - immunology ; Basic Medicine ; Beta cells ; Cell surface ; Child ; Child, Preschool ; Children ; Clinical Medicine ; Deoxyribonucleic acid ; Diabetes ; Diabetes mellitus ; Diabetes mellitus (insulin dependent) ; Diabetes Mellitus, Type 1 - genetics ; Diabetes Mellitus, Type 1 - immunology ; Diabetes Mellitus, Type 1 - pathology ; Diabetes Mellitus, Type 1 - virology ; Diseases ; DNA ; DNA viruses ; Endocrinology and Diabetes ; Endokrinologi och diabetes ; Enterovirus - immunology ; Enterovirus - isolation & purification ; Enterovirus - pathogenicity ; Enteroviruses ; Feces - virology ; Female ; Genetic aspects ; Health aspects ; Health risks ; Humans ; Infant ; Infections ; Insulin ; Insulin - metabolism ; Insulin-Secreting Cells - immunology ; Insulin-Secreting Cells - virology ; Islets of Langerhans - immunology ; Islets of Langerhans - pathology ; Islets of Langerhans - virology ; Klinisk medicin ; Male ; Medical and Health Sciences ; Medical Genetics ; Medicin och hälsovetenskap ; Medicinsk genetik ; Medicinska och farmaceutiska grundvetenskaper ; Mutation ; Mutation rates ; Pancreas ; Pancreas - immunology ; Pancreas - pathology ; Pancreas - virology ; Pathogenicity ; Pathogens ; Periodic variations ; Periodicity ; Ribonucleic acid ; Risk factors ; RNA ; RNA viruses ; RNA, Viral - isolation & purification ; Serotypes ; Type 1 diabetes ; Virulence ; Viruses
Es parte de: Nature medicine, 2019-12, Vol.25 (12), p.1865-1872
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Author Contributions
K.V., K.F.L., M.R., J.T., A.G.Z., J.-X.S., A.L. B.A, W.A.H., D.A.S., J. P.K., H.H., R.E.L. designed the study; M.R., W.A.H., J.T., A.G.Z., J.-X.S., B.A., A.L., H.H., K.V., K.F.L., J.P.K., participated in patient recruitment and diagnosis, sample collection, generation of the metadata; J.F.P., R.E.L., N.J.A., M.C.W., M.C.R., X.T., R.A.G. generated and processed the raw sequencing data; K.F.L., K.V., H.H., R.E.L., performed the data analysis, data interpretation, and figure generation; K.V., K.F.L., H.H., R.E.L., wrote the paper; and all authors contributed to critical revisions and approved the final manuscript.
Descripción: Viruses are implicated in autoimmune destruction of pancreatic islet β cells, which results in insulin deficiency and type 1 diabetes (T1D) . Certain enteroviruses can infect β cells in vitro , have been detected in the pancreatic islets of patients with T1D and have shown an association with T1D in meta-analyses . However, establishing consistency in findings across studies has proven difficult. Obstacles to convincingly linking RNA viruses to islet autoimmunity may be attributed to rapid viral mutation rates, the cyclical periodicity of viruses and the selection of variants with altered pathogenicity and ability to spread in populations. β cells strongly express cell-surface coxsackie and adenovirus receptor (CXADR) genes, which can facilitate enterovirus infection . Studies of human pancreata and cultured islets have shown significant variation in enteroviral virulence to β cells between serotypes and within the same serotype . In this large-scale study of known eukaryotic DNA and RNA viruses in stools from children, we evaluated fecally shed viruses in relation to islet autoimmunity and T1D. This study showed that prolonged enterovirus B rather than independent, short-duration enterovirus B infections may be involved in the development of islet autoimmunity, but not T1D, in some young children. Furthermore, we found that fewer early-life human mastadenovirus C infections, as well as CXADR rs6517774, independently correlated with islet autoimmunity.
Editor: United States: Nature Publishing Group
Idioma: Inglés

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Prospective virome analyses in young children at increased genetic risk for type 1 diabetes

United States: Nature Publishing Group

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