The role of persistent viral infections in the development of immune dysregulation in children with primary or secondary immunodeficiencies
Friday 12 June 2009
Project
Common Variable Immunodeficiency (CVID) is a primary immunodeficiency characterized by an impaired production of antibodies. Since the clearance of some enteropathogenic viruses is largely antibody-dependent, CVID patients are prone to persistent viral gastrointestinal infections. Recently, sensitive RT-PCR has become available, allowing rapid and sensitive detection of enteropathogenic viruses. Additionally, CVID patients sometimes develop autoimmune enteropathy. It is an intriguing question why these immune deficient patients paradoxically display reactivity against self-antigens.
This susceptibility to auto- or allo-immune disease is also seen in secondary immunodeficiency: allogeneic stem cell transplantation (SCT) is a last treatment option for disease conditions such as refractory leukemia and lymphoma. SCT patients receive chemotherapy, making them immuno-compromised for a long period. During this period, they are prone to acquired infections or reactivations of viral infections, e.g. in the gastro-intestinal tract. The most important immune disease following SCT is Graft versus Host Disease (GvHD) in the liver, skin, lungs and gut, which is a common and life-threatening complication.
Our recent patient findings suggest that chronic immune activation, due to continuous viral replication in combination with inadequate humoral immunity, may cause immunological dysbalance, eventually leading to auto-immunity.
Hence, the aim of this project is to investigate whether persistent viral gastrointestinal tract infections may trigger immune dysregulation in the immunocompromised patient.
Stool samples of CVID or SCT patients will be tested for selected viruses (e.g. parechovirus, norovirus), using novel techniques such as RT-PCR. The project will be performed in close collaboration with the department of Pediatric Immunology and Infectious Diseases in the Wilhelmina Children’s Hospital. Results of stool PCR will be related to clinical and histological findings, in order to quantify the possible relation between chronic enteric viral carrier state and gut inflammatory disease states.
Techniques
Stool sample preparation, virus isolation, neutralization assays, TaqMan real-time PCR, sequence analysis
Duration
6 or 9 months
Contact
Dr. A.M.J. Wensing, A.M.J.Wensing@umcutrecht.nl, 088 75 565 26, pager 3611
More info
Department of Pediatric Immunology: J.M.vanMontfrans@umcutrecht.nl
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