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

NCT06169150 | Recruiting

• 2 other identifiers: 10001511001511-I
• Study Type: observational
• Target: 350
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Immune system and nervous system have significant interaction so that People with immunity diseases can have complications that affect the nervous system and people with some neurological disease may have defects in their immune system.These complications can affect many body functions, including how they move, walk, think, and feel. Researchers do not fully understand how immune diseases affect the nervous system. By learning more, they hope to create more effective treatments. Objective: To learn more about the interaction between immune and nervous system and how immunity disease affect the nervous system. Eligibility: People aged 2 years and older with an immunity disease. Their healthy biological relatives and other healthy volunteers are also needed. Design: Participants will be screened. Blood will be drawn for research. They may have imaging scans. Adults may undergo lumbar puncture: A needle will be inserted into their back to collect fluid from the space around the spinal cord. The imaging scans and lumbar puncture will be optional for healthy relatives and volunteers. All participants will have 1 study visit per year for 5 years. They will be asked to donate samples of body fluids at each visit. Blood samples are required for the study. All other donations are optional. These may include saliva, urine, breast milk, stool, vaginal secretions, and wound drainage. Affected participants may be asked for a skin biopsy: A small sample of skin will be removed. They may also be photographed or videotaped to record the symptoms of their disease. Tests for each study visit may be spread over several days, if needed. Visits may be at the clinic. Participants may also collect their own samples at home and send them to the researchers....

Conditions

Nervous System Disease; Immune System Disease

Keywords

Errors Of Immunity; Neurological Diseases; Neuroinflammation; Neuroinfections; Neurodegeneration; Primary Immunodeficiency; Neuropathogenesis; Inborn Errors of Immunity

Outcome Measures

Primary Outcomes (2)

• 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.

  Clinically characterize neurologic manifestations of errors of immunity via neurologic exam and neuroimaging.

  Through end of participation.

• Characterization of inherited or acquired errors of immunity in participants with rare neurologic diseases.

  Determine genetic defects in participants.

  Through end of participation.

Secondary Outcomes (1)

• 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.

  Through end of participation.

Study Arms (2)

Healthy Controls

Biological relatives or unrelated persons without a known diagnosis of neuroinfectious disease or neuroinflammation.

Primary or acquired immunodeficiency

Known or suspected infection or inflammation of the nervous system or post infection sequelae, or is at risk of developing such a neurologic complication.

Eligibility Criteria

• Age: 2 Years - 120 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Participants will be recruited from NIH protocols 15-N-0125 (Natural History Study of Inflammatory and Infectious Diseases of the Nervous System) and 93-I-0119 (Detection and Characterization of Host Defense Defects), or from referrals. Biological relatives of affected participants may be enrolled on this study as controls.

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Nervous System Diseases; Immune System Diseases; Neuroinflammatory Diseases; Nerve Degeneration; Primary Immunodeficiency Diseases

Condition Hierarchy (Ancestors)

Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Immunologic Deficiency Syndromes

Study Officials

• Farinaz Safavi, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kelsey L Yoo, P.A.-C

CONTACT

(240) 656-0596; kelsey.yoo@nih.gov

Farinaz Safavi, M.D.

CONTACT

(301) 496-4952; farinaz.safavi@nih.gov

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 11, 2023
• First Posted: December 13, 2023
• Study Start: January 12, 2024
• Primary Completion (Estimated): January 1, 2043
• Study Completion (Estimated): October 1, 2043
• Last Updated: September 25, 2025

Record last verified: 2025-09-23

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD will be shared into GEO following publication of manuscripts.
• Access Criteria: GEO is an open-access database.

Locations

US (1)