Functional Genomics in Early Autoimmunity
Autor: | Evie Melanitou |
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Přispěvatelé: | Immuno-Hématologie et Immunopathologie, Institut Pasteur [Paris] (IP), Special acknowledgments are due to Dr. George Eisenbarth, in whose laboratory at the Barbara Davis Center for Childhood Diabetes, Denver, CO, I initiated this work during my sabbatical. I am thankful for his constant support. I thank also Rebecca Brown for her help with the transcriptome data analysis., Institut Pasteur [Paris] |
Jazyk: | angličtina |
Rok vydání: | 2005 |
Předmět: |
Time Factors
MESH: Mice Inbred NOD Insulin Antibodies MESH: Lymph Nodes Disease [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC] medicine.disease_cause Autoimmunity Mice 0302 clinical medicine MESH: Pregnancy Autoimmune Process Mice Inbred NOD Pregnancy [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases MESH: Autoantibodies heterocyclic compounds MESH: Animals Oligonucleotide Array Sequence Analysis NOD mice 0303 health sciences General Neuroscience MESH: Genomics autoimmunity MESH: Genetic Predisposition to Disease food and beverages Genomics MESH: Pancreas [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism 3. Good health MESH: Insulin Antibodies Female MESH: Diabetes Mellitus Type 1 Radioimmunoassay insulin autoantibodies Biology General Biochemistry Genetics and Molecular Biology MESH: Radioimmunoassay 03 medical and health sciences History and Philosophy of Science MESH: Autoimmunity medicine Genetic predisposition Animals Genetic Predisposition to Disease Pancreas MESH: Mice Autoantibodies 030304 developmental biology Autoimmune disease Type 1 diabetes pancreatic lymph nodes MESH: Time Factors Autoantibody medicine.disease maternal [SDV.GEN.GA]Life Sciences [q-bio]/Genetics/Animal genetics Diabetes Mellitus Type 1 [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics Immunology MESH: Oligonucleotide Array Sequence Analysis Lymph Nodes transcriptome MESH: Female type 1 diabetes mellitus 030215 immunology |
Zdroj: | Annals of the New York Academy of Sciences Annals of the New York Academy of Sciences, 2005, Autoimmunity: Concepts and Diagnosis at the Cutting Edge 1050, pp.64-72. ⟨10.1196/annals.1313.008⟩ Annals of the New York Academy of Sciences, Wiley, 2005, Autoimmunity: Concepts and Diagnosis at the Cutting Edge 1050, pp.64-72. ⟨10.1196/annals.1313.008⟩ |
ISSN: | 0077-8923 1749-6632 |
Popis: | International audience; The molecular mechanisms initiating the autoimmune process in type 1 diabetes mellitus (T1DM) remain unknown, and studies aiming to address this question have been compromised by the difficulty of predicting the disease at an early age both in humans and in animal models. An additional hindrance in selecting individuals at an early age has been the complex genetic inheritance of autoimmune diabetes, implicating not only several genes but also environmental factors. We have previously demonstrated the predictive value of insulin autoantibodies (IAAs) at an early age, between three to five weeks in the NOD mouse. Animals positive for early appearance of IAAs (E-IAAs) develop auto-immune diabetes earlier. We showed a correlation between the presence of IAAs in the mothers during pregnancy, E-IAAs in the litters, and the early appearance of T1DM. NOD mice, E-IAA–positive, within litters from IAA-positive mothers during pregnancy, develop diabetes earlier and at a much greater rate than animals that are IAA-negative and from IAA-negative mothers. The molecular mechanisms responsible for this early autoimmune subphenotype were addressed by a global approach to differential gene expression analysis in the pancreatic lymph nodes (PaLNs). Although the data analysis is currently in progress, gene expression signatures were observed that are characteristic for PaLNs with regard to the presence or absence of IAAs. Overall, these data are consistent with the hypothesis of an early environmental influence from the autoimmune maternal environment on the genetic predisposition of the offspring, characterized by specific gene signatures leading to autoimmune disease. |
Databáze: | OpenAIRE |
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