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Functional Genomics in Early Autoimmunity
Author(s) -
MELANITOU EVIE
Publication year - 2005
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1313.008
Subject(s) - autoimmunity , functional genomics , genomics , computational biology , biology , medicine , immunology , genetics , genome , immune system , gene
A bstract : 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 autoimmune 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.