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Title page for ETD etd-08082006-162821


Type of Document Dissertation
Author Maas, Kevin Henry
Author's Email Address Kevin.Maas@vanderbilt.edu
URN etd-08082006-162821
Title Characterization of an Autoimmune Gene Expression Signature
Degree PhD
Department Microbiology and Immunology
Advisory Committee
Advisor Name Title
James Thoma. Committee Chair
Jennifer Pietenpol Committee Member
Mark Boothby Committee Member
Nancy Olson Committee Member
Thomas Aune Committee Member
Keywords
  • Rheumatoid Arthritis
  • Systemic Lupus Erythematosis
  • p53
  • DNA damage response
  • Autoimmunity
  • Microarray
  • DNA microarrays
  • Autoimmune diseases -- Genetic aspects
  • Immunogenetics
Date of Defense 2004-06-25
Availability unrestricted
Abstract
MICROBIOLOGY AND IMMUNOLOGY

CHARACTERIZATION OF AN AUTOIMMUNE

GENE EXPRESSION SIGNATURE

KEVIN MAAS

Dissertation under the direction of Professor Thomas Aune

Autoimmune diseases affect approximately 5% of the human population and are believed to arise from immune mediated attack against self-antigen. Microarray studies demonstrate highly reproducible gene expression signatures in peripheral blood mononuclear cells (PBMC) of patients with a range of autoimmune disorders. Neither in vivo recapitulation of an immune response to foreign antigen or disease duration accounted for the autoimmune gene expression signature. However, unaffected first-degree relatives also contained this gene expression signature, suggesting that it arose from a heritable trait(s). The autoimmune signature includes, at least in part, under-expressed genes that encode proteins that inhibit cell cycle progression and stimulate apoptosis. We found that reduced TP53 gene expression and p53 protein levels are associated with selective loss of lymphocyte radiation-induced apoptosis in patients with rheumatoid arthritis. We hypothesize that these liabilities may contribute to autoimmunity.

Approved______________________________________ Date_________

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