Activation and Function of Eosinophils in Conditions With Blood or Tissue Eosinophilia

Study Description: This study is designed to collect data and clinical samples from participants with elevated eosinophil counts in the peripheral blood or tissues or their relatives to enhance our understanding of the mechanisms driving eosinophilia and eosinophil activation in patients with a wide range of eosinophilic disorders with the ultimate goal of improving diagnostics and identifying novel treatment modalities for these patients. Eosinophilic participants will undergo an extensive clinical evaluation at baseline and at least yearly thereafter focused on the identification of the cause of eosinophilia and the presence of end organ manifestations. Blood, bone marrow, tissue, and/or body fluids will be collected for research purposes at initial and follow-up visits to address broader questions relating to the varied etiologies of eosinophilia, biomarkers of disease activity and eosinophil activation, and the functional role of eosinophils in homeostasis and disease pathogenesis. While this protocol is not primarily designed to study treatment of eosinophilic patients, the clinical and immunological responses to therapy will be monitored. This protocol will also allow clinical and laboratory evaluation of family members of subjects with eosinophilia to help identify genetic causes of eosinophilia and to provide controls for immunologic studies. Objectives: Primary Objective: to understand the mechanisms driving eosinophilia and eosinophil activation in patients with a wide range of eosinophilic disorders Secondary Objectives: 1. To develop a diagnostic algorithm that accurately classifies eosinophilic patients by underlying etiology 2. To determine the mechanisms underlying eosinophil activation and recruitment to the blood and tissues 3. To understand the mechanisms of action of therapeutic agents used or in development for the treatment of HES 4. To assess the signs and symptoms experienced by patients with HES Exploratory Objectives: 1. To investigate the multifunctional role of eosinophils in settings other than HES 2. To understand the long-term effects of eosinophilia in patients with HES 3. To assess the effects of race, sex, ethnicity, and environmental factors on the prevalence and clinical manifestations of eosinophilic disorders Endpoints: Primary Endpoint: Identification and characterization of clinical and genetic variants of hypereosinophilic syndromes (HES) Secondary Endpoints: 1\. Identification of laboratory and clinical tests that distinguish between clinical and genetic variants of HES 2a. Identification of biomarkers of disease activity and specific organ involvement in eosinophilic disorders 2b. Identification of new therapeutic targets for the treatment of HES 3\. Delineation of the effects of therapeutic agents on eosinophil development, activation, recruitment to tissues and/or apoptosis 4\. Creation of a patient-related outcomes questionnaire for use in future treatment studies of HES Exploratory Endpoints: 1. Description of the consequences of eosinophilia and/or eosinophil depletion in the context of varied immunologic and inflammatory settings 2. Collection of standardized longitudinal data on disease activity and outcome in patients with hypereosinophilia. 3. Comparison of prevalence and clinical manifestations of eosinophilic disorders among varied subpopulations of patients