The goal of Project 3 is to comprehensively characterize immune systems of patients who are known to have abnormal immune systems, and to compare their immune responses with those of normal subjects. We will challenge the immune system by vaccinating patients with influenza vaccines, characterizing the response of an abnormal immune system to this perturbation. Project 3 will study patients with Common Variable Immunodeficiency Disease (CVID) and Systemic Lupus Erythematosus (SLE), prototypic diseases of immune dysregulation. There are 3 aims: (i.) to develop and validate a multistrain influenza and HINIv antigen microarray for profiling antibodies in vaccinated human subjects. We will clone and express major antigens from influenza strains, which will then be printed onto derivatized glass microscope slides. Arrays will first be validated using commercially-available monoclonal and polyclonal antibodies, then further validated using serum derived from normal subjects vaccinated with HINIv and seasonal flu vaccines;(ii.) to compare the baseline function of the immune system in normal human subjects with the baseline function of the immune system in immunosuppressed patients. We will create a comprehensive database of immune function measurements in CVID and in SLE, comparing the responses with normal subjects (Core C), and vaccinated subjects studied in Projects 1-7. We will take advantage of the Stanford Immunologic and Rheumatic Disease Registry and Biospecimen Repository, and the Adult and Pediatric Immunodeficiency Clinics for access to clinical samples, (iii.) to compare the global response of the immune system in normal subjects with the response in immunosuppressed patients (CVID, mild vs severe SLE, and therapeutic immunosuppression) when immunized with seasonal and HINIv influenza vaccines. We will test the hypothesis that a subset of healthy individuals has immune deflcit(s) similar to those observed in patients with autoimmunity, immunodeficiency disorders, or who are immunosuppressed with drugs such as glucocorticoids. We further hypothesize that this subset of patients will have an abnormal response to vaccine challenge with HI Nl v or seasonal flu vaccines. Results of Project 3 may improve future vaccination strategies for patients with immune deficiencies, and may identify subsets of """"""""normal"""""""" patients who are unlikely to respond to existing vaccine protocols.
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