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....

* 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.