Detection and Characterization of Neurologic Manifestations of Inborn and Acquired Errors of Immunity

Study Description:

In this study, we will characterize clinical neurologic presentations of patients with known or unevaluated primary and acquired errors of immunity. Investigating the underlying mechanisms of neurologic diseases and their genetic and immunologic bases requires periodic clinical evaluation of these patients and research analyses of their biospecimens. These biospecimens include blood, cerebrospinal fluid (CSF), urine, saliva, skin, breast milk, stool, vaginal specimens, and wound drainage. Magnetic resonance imaging (MRI) of the neural axis may also be done. Data and excess biospecimens from routine clinical care may also be collected and used for research. We propose to evaluate patients who either have or are suspected of having immune defects or other types of host defense defects with neurologic presentations. Unaffected biological relatives and healthy volunteers will also be enrolled as controls for research analyses.

Primary Objectives:

• Clinically characterize neurologic manifestations of errors of immunity via neurologic exam and neuroimaging.
• Determine genetic defects in participants.

Secondary Objective:

Characterize immune cells in CSF and blood.

Primary Endpoints:

• Clinical characterization of neurologic manifestations in participants with recognized and unrecognized errors of immunity based on neurologic examination, neuroimaging, and other necessary neurologic tests depending on clinical presentation.
• Characterization of inherited or acquired errors of immunity in participants with rare neurologic diseases.

Secondary Endpoint:

Characterization and comparison of immunologic phenotypes of both CSF and blood in participants with errors of immunity vs healthy controls, and longitudinally in participants using cellular and molecular immunologic techniques, including but not limited to immune cell phenotype, transcriptomics, metagenomics, and immune biomarkers.

• INCLUSION CRITERIA:

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

• Aged >=2 years. To be seen at the NIH CC, participants must be >=3 years of age.
• Willing to allow specimens and data to be stored for future research.
• Willing to allow genetic testing on their biospecimens.
• Able to provide informed consent (for ages >=18 years) or has parent(s) or guardian(s) who can provide permission to participate on their behalf (for ages <18 years).

• Decisionally impaired affected adult participants may have a legally authorized representative (LAR) to provide informed consent on their behalf.

Additional Inclusion Criterion for Affected Participants:

Has a primary or acquired immunodeficiency and known or suspected infection or inflammation of the nervous system or post-infection sequelae, based on clinical or imaging data provided by the referral facility, or is at risk of developing such a neurologic complication. For the purpose of this study, neuroinfectious disease or neuroinflammation is defined as any of the following:

• Any neurologic symptoms accompanied by CSF with evidence of inflammation (which may include pleocytosis, hypoglycorrachia, elevated protein, or other evidence of intrathecal immune activation, including immunoglobulin [Ig] G index or presence of oligoclonal bands).
• Systemic infection or inflammatory disease with neurologic involvement.
• Neuroimaging suggestive of infection or inflammation (for example, presence of contrast-enhancing lesions on CT or MRI).
• Clinical presentation suggestive of infection or inflammatory process of the nervous system without better explanation.
• History of infection or inflammatory process of the nervous system.

Affected participants must also have their own primary health care provider to manage their condition outside the NIH.

Additional Inclusion Criteria for Biological Relatives and Healthy Volunteers:

• Is either a biological relative of an affected participant or is unrelated.
• Does not have a known diagnosis of neuroinfectious disease or neuroinflammation.

Exclusion criteria

An individual who meets any of the following criteria will be excluded from participation in this study:

• Pregnant (for biological relatives and healthy volunteers).
• Any condition that, in the judgment of the investigator, may put the participant at undue risk or make them unsuitable for participation in the study.