Sample Collection for Systems Evaluation of Patients With Unknown or Incompletely Characterized Immune Defects

Description

Immunological disorders predispose affected individuals to a myriad of complications, including infection, immune dysregulation with autoimmune disease and aberrant inflammatory responses, and malignancy. Advances in genetic testing have propelled the discovery of the genetic underpinnings of numerous immunodeficiencies. However, a more complete picture of the immune system is needed to better characterize patients that present with the signs and symptoms of immunodeficiency or immune dysregulation in whom there is no identifiable genetic diagnosis. Many of our diagnostic tools, such as characterization of cell subset frequencies, look at only one parameter in the immune system, which is typically insufficient to capture the system s complexity. Systems immunology is a field of research aimed to identify and understand how the different components of the immune system work together in a coordinated manner to achieve its functions, such as protecting against pathogens and mounting effective responses after vaccination. The goal of this study is to collect patient samples to more deeply phenotype these individuals at the molecular and cellular levels using novel technologies in order to generate hypotheses regarding disease etiologies and mechanisms in subjects with an immune disorder without complete characterization or clear genetic etiology. We also aim to validate a specific observation seen in a previous study of patients with known monogenic immunological disorders. In the long-term, hypotheses generated in this study that address clinically significant, actionable questions will be pursued as separate investigations.

This hypothesis-generating sample collection study will recruit patients with unknown or incompletely characterized immune defects and their unaffected relatives. Under this protocol, samples will be collected at the NIH Clinical Center or mailed in for analysis using systems biology approaches to generate hypotheses regarding the potential etiologies and mechanisms of these immune defects. Initially, all subjects will give a blood sample and may give additional samples including saliva, stool, and skin punch biopsies. Subjects will be enrolled for 5 years and may be asked to give additional samples based on scientific need or changes in clinical status. Findings relevant to subjects health and medical care will be returned to them and referring healthcare providers.