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Replies to post #333094 on Anavex Life Sciences Corp (AVXL)
Infections and Immune Function in Mitochondrial Diseases
Patients diagnosed with a mitochondrial disease often experience more infections that are more frequent and/or severe. In some cases, researchers and clinicians have been able to identify problems in the patient’s immune system that contribute to their infection susceptibility.
Patients with mitochondrial diseases can have issues related to the decreased production and function of the body’s white blood cells and antibodies that need to be generated to fight infection. Clinicians cannot always predict which child will manifest problems with their immune system. There are some genetic deficiencies associated with immune dysfunction, but they are not a consistent predictor of immune response problems in patients.
RATIONALE: The generation of an immune response to infection requires enormous amounts of energy in the form of ATP. Children with mitochondrial disease (MD) have limited ability to produce ATP. Since ATP is generated by the mitochondria, we hypothesize that children with mitochondrial dysfunction (MD) have repeated infections due to the limited availability of ATP for the generation of a protective immune response.
METHODS: Patients with biopsy proven MD were evaluated. Clinical history, immunoglobulin subsets and subclasses, specific antibody responses, lymphocyte subsets and functional assays were analyzed.
RESULTS: Twenty-nine children (1-16 years) with MD were evaluated. Over fifty percent had repeated sino-pulmonary infections. Three (10%) had bacteremia/sepsis with Serratia sp., Pseudomonas sp., MRSA, Stenotrophomonas sp., C. tropicalis, C. albicans, C. parapsilosis and E. cloacae. Of these 3 patients, only one had a functional humoral defect and 12 episodes of bacteremia/sepsis. Ten children (34%) had hypogammaglobulinemia, and a total 3, (10%), did not respond to immunization with polysaccharide antigens. All patients had adequate distribution of CD3, CD4, CD8, CD19, and CD56 cells as well as in vitro proliferation to mitogens.
CONCLUSIONS: Children with MD exhibit immunodeficiency characterized by recurrent sinopulmonary infections and bacteremia/sepsis. It remains to be determined if this is a static defect or if the increased susceptibility to infections is related to metabolic stressors and increased ATP demands.
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