EX-VIVO RESPIRATORY BURST RESPONSE TO A. FUMIGATUS AFTER STEM CELL TRANSPLANT

University Of Chicago, Chicago IL

Investigators

Abstract

DESCRIPTION (provided by applicant): Allogeneic stem cell transplantation is a life saving procedure for a variety of hematologic malignancies. Unfortunately, long term survival is significantly impacted by the development of invasive fungal infections. The risk of developing an invasive fungal infection persists well after engraftment, suggesting the presence of a functional neutrophil abnormality. We aim to identify and characterize abnormal pathogen-specific neutrophil responses after transplantation. Ultimately, this will allow us to apply prophylactic and therapeutic strategies designed to limit the infectious complications of this life saving therapy. Specific Aim #1: To characterize pathogen-specific neutrophil respiratory burst responses after allogeneic stem cell transplantation. Examination of neutrophil respiratory burst after stimulation with various Aspergillus forms (conidia, germinating conidia, and hyphae) will yield specific information about the nature of neutrophil responses after allogeneic stem cell transplantation. Patients with significantly decreased respiratory burst will be selected to undergo further mechanistic testing (Specific Aim #2). Specific Aim #2: To determine mechanisms which contribute to impaired pathogen-specific neutrophil respiratory burst responses after allogeneic stem cell transplantation. Patients with decreased respiratory burst will undergo further testing to determine whether decreased neutrophil response is due to abnormalities in pattern-mediated recognition, opsonin-mediated recognition, or post-receptor function, and whether these responses are reversible with cytokine stimulation. Public Health Relevance: Over 200,000 allogeneic transplants have been performed. However, long term survival after transplantation remains low, in part due to severe, life-threatening infections. Currently, there is a paucity of information regarding the mechanisms behind host susceptibility to these infections. This study aims to contribute to the understanding of functional immune abnormalities after allogeneic stem cell transplantation in order to provide better long term outcomes for these patients.