* INCLUSION CRITERIA:
Participants enrolled onto this protocol must meet all of the following criteria:
1. Age 0-99 years.
2. Meets 1 of the following criteria:
1. Patient with a clinical diagnosis of a form of PID (either known or suspected). PID may be defined by laboratory and/or clinical findings on 2 or more occasions that are consistent with a defect in innate or adaptive immunity. Specific PIDs are defined by the guidelines of the International Union of Immunological Societies.
2. Biological relative of an individual meeting criterion 2a, with no clinical evidence of having a PID. Relatives may be mother, father, siblings, children, grandparents, aunts, uncles, or first cousins to an individual with a known or suspected PID.
3. Able to provide informed consent.
4. Willing to allow genetic testing and allow biospecimens to be modified into induced pluripotent stem (iPS) cells.
5. Willing to allow storage of samples and data for future research.
EXCLUSION CRITERIA:
Individuals meeting any of the following criteria will be excluded from study participation:
1. History of secondary causes of immunodeficiency (eg, HIV infection, immunodeficiency from chronic use of immunosuppressive or chemotherapeutic agents), at the discretion of the investigator.
2. Any condition that, in the opinion of the investigator, contraindicates participation in this study.
INCLUSION/EXCLUSION OF SPECIAL POPULATIONS:
Children: Children are eligible to participate in this study because PIDs may present in early childhood and results of some research tests may inform participants future medical care. Additionally, the study poses no more than minimal risk.
Pregnant women and neonates: Pregnant women can participate in this study. Research testing on samples from pregnant women may help us learn about changes in the immune systems of immunodeficient patients during pregnancy, which is important knowledge that could not be obtained from nonpregnant individuals. Research testing of pregnant women with known or suspected PIDs could provide insight into the fetus s health risks, which may help guide clinical management during and after pregnancy. We may request cord blood samples at delivery to process right away or freeze. Cord blood is a unique source of stromal cells that may be characterized or modified for research purposes. Additionally, this study poses no more than minimal risk, including to participants who are pregnant and their fetuses. Similarly, neonates (including nonviable neonates or those of uncertain viability) may be enrolled in this study as it does not involve more than minimal risk and blood volumes will be limited based on the clinical status of each participant. Each individual providing consent will be fully informed regarding the reasonably foreseeable impact of the research on the neonate, and individuals engaged in the research will have no part in determining the viability of a neonate. Further, neonates of uncertain viability are eligible because all the following criteria are met:
* Many PIDs are rare and present early in life, and it is possible that the manifestations of a known or suspected PID may impact the viability of the neonate. Research testing of neonates with known or suspected PIDs could provide insight into current and future health risks, which may provide guidance for medical management and thus benefit the neonate and possibly enhance the probability of survival.
* The only risks of study participation are the risks of blood draw. When possible, blood for this study will be collected at the time of clinically indicated blood draws so that there is no additional needlestick, and blood volumes will be limited based on the clinical status of each participant. Collection of blood is the only possible method to conduct the research testing under this protocol that may directly benefit the neonate by revealing insights about health risks and medical management. Thus, the risk is the least possible for achieving that objective.
* The legally effective informed consent of either parent of the neonate or, if neither parent is able to consent because of unavailability, incompetence, or temporary incapacity, the legally effective informed consent of either parent's legally authorized representative is obtained, except that the consent of the father or his legally authorized representative need not be obtained if the pregnancy resulted from rape or incest.
Nonviable neonates are also eligible because all the following criteria are met:
* Vital functions of the neonate will not be artificially maintained.
* The research will not terminate the heartbeat or respiration of the neonate.
* Blood will only be collected from nonviable neonates at the time of clinically indicated blood draws so that there is no additional needlestick, and blood volumes will be limited based on the clinical status of each participant. Therefore, there will be no added risk to the neonate resulting from the research.
* As described above, many known or suspected PIDs are rare and can present early during life, and it is possible that their manifestations may impact the viability of the neonate. This protocol aims to achieve characterization of such disorders, and this aim could not be achieved for certain disorders if nonviable neonates are excluded. Thus, the purpose of the research is the development of important biomedical knowledge that cannot be obtained by other means.
* The legally effective informed consent of both parents of the neonate will be obtained.
Decisionally impaired adults: Adults who are unable to consent are excluded from study participation. Enrolled participants who temporarily lose the ability to consent during study participation may continue in the study in accordance with NIH Human Research Protections Program (HRPP) Policy 403 Research with Subjects Lacking Capacity to Consent; the study poses no more than minimal risk and may hold a prospect of direct benefit as results of some research tests may inform participants future medical care. However, enrolled participants who permanently lose the ability to consent during study participation will be withdrawn.
