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

 The immune system defends the body against disease. It has many different parts spread out in

 the body, including in the blood and skin. To learn more about it, researchers want to study
 samples from people with healthy immune systems and people with conditions that affect how
 the immune system works.

 Objective:

 To learn about how the different parts of the immune system come together to make a whole.

 Eligibility:

 People age 2 and older who have a condition that affects the immune system or have a family
 member with such a condition.

 Design:

 Participants will be screened with medical and medicine review. Other lab tests may also be
 reviewed. Some participants will take a pregnancy test.

 Participants will give blood samples. They may also give saliva, stool, and urine samples.

 A sterile cotton swab may be rubbed over their skin or inside the cheek or nose to collect
 cells.

 If participants have samples collected as part of their regular medical care, their doctor
 may be asked to send parts of the samples that otherwise would be thrown away. These samples
 may be from biopsies, endoscopies, or other procedures.

 Some participants may have optional skin punch biopsies. For this, their skin is numbed. Then
 a tool removes 1 or 2 small pieces of skin from the forearm or thigh.

 Participants medical records will be checked to see if they have any changes in their health
 over time. If they have a study visit, they may talk about their medical history and have a
 physical exam.

 Participation lasts 5 years....
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.
-  INCLUSION CRITERIA:

 1. Aged greater than or equal to 2 years.

 2. Meets 1 of the following criteria:

 a. Patient with a suspected or known/molecularly defined but incompletely
 characterized immune disorder (as determined by a referring NIH study staff
 member) AND meeting at least one of the following:

 i. within 1 year of screening, abnormal immune function demonstrated by at least
 one laboratory test result outside the normal range

 ii. history of severe or atypical infection, immune dysregulation (defined as
 autoimmunity, lymphoproliferation, or HLH), or autoinflammatory symptoms (defined
 as episodic fever often associated with dermatitis, gastrointestinal symptoms,
 and arthropathy).

 b. Biological unaffected relative of an individual meeting criterion 2a but who
 does not meet criterion 2a himself/herself. Unaffected relatives may be mother,
 father, siblings, children, grandparents, aunts, uncles, or first cousins to the
 individual.

 3. Willing to allow storage of samples and data for future research.

 4. For patients, currently or previously enrolled on an NIH protocol that performs
 WES or WGS and that allows sharing of sequence data.

 5. For unaffected relatives, able to provide informed consent.

 EXCLUSION CRITERIA:

 Individuals meeting any of the following criteria will be excluded from study
 participation:

 1. History of secondary causes of immunodeficiency or dysregulation (e.g., HIV infection,
 immunodeficiency from chronic use of immunosuppressive or chemotherapeutic agents), at
 the discretion of the investigator.

 2. Pregnancy.

 3. Any condition that, in the opinion of the investigator, contraindicates participation
 in this study.