The purpose of this project is to study patients with abnormal host defense. In FY'97 we continued our long term studies on natural history and disease pathogenesis on patients with abnormal phagocyte function. These included patients with chronic granulomatous disease of childhood, hyperimunoglobulin E-recurrent infection syndrome (Job's), leukocyte adhesion deficiency and other patients with recurrent infections who do not fall into a specifically defined disease category. This year we continued the phase IV clinical trial on the effect of interferon- gamma on the growth and development of children with chronic granulomatous disease of childhood and failed to note any adverse reactions. We have continued our studies on a 15 yo girl with recurrent life threatening bacterial infections who is refractory to the effects of endotoxin lipopolysaccharide (LPS) in vivo and in vitro. Our studies in this patient demonstrating abnormal febrile response to LPS and defective responses for TNF-alpha, IL-6, IL-8, lactoferrin and G-CSF were completed and published this year. We are now focusing our attention to the molecular basis for endotoxin hyporesponsiveness in this patient. Preliminary data indicates the defect involves the NFKB system. Although the precise defect has not yet been identified the data suggest involvement of a kinase system involved in protein phosphorylation.
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