Immune Regulation in Patients With Common Variable Immunodeficiency and Related Inborn Errors of Immunity (IEI)

NCT00001244 | Recruiting

• 2 other identifiers: 89015889-I-0158
• Study Type: observational
• Target: 500
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to understand the causes and progression of Common Variable Immunodeficiency (CVID) and related inborn errors of immunity (IEI). These are conditions where the immune system does not function properly, leading to frequent infections and other complications such as gastrointestinal inflammation, lung and liver disease, autoimmune conditions, and an increased risk of certain cancers. By studying patients with CVI and related immune disorders, we hope to develop better ways to diagnose, treat, and prevent complications associated with these conditions. Patients diagnosed with CVID or related immune disorders must be referred by their physician and medical records reviewed by the study team to confirm eligibility to participate in this study. Once enrolled, participants will undergo various tests, including blood draws, physical exams, and imaging studies like CT scans to track changes over time. We may collect samples such as blood, urine, stool, or saliva for research purposes. If a surgical procedure or biopsy is performed because it is medically necessary, we may collect an additional sample for research testing. Family members of patients may be asked to provide blood samples for comparison. Some tests may be done remotely if participants or family members cannot travel to the study site. Who Can Participate

• Patients diagnosed with CVI or related IEI, such as X-linked agammaglobulinemia, Blau Syndrome or Yao Syndrome.
• Participants must be at least 2 years old.
• Family members of patients may include parents, siblings, grandparents, children, aunts, uncles, and cousins.
• Pregnant women already enrolled in the study will continue to participate, but new pregnant participants will not be enrolled. Potential Risks and Benefits
• Risks: Blood draws may cause discomfort, bruising, or infection. Apheresis may cause dizziness, nausea, or muscle cramps; this procedure is to collect specific cells in the blood and is infrequently done on this protocol. Extra biopsies during clinically indicated procedures may increase the risk of complications; they will only be collected after the medically necessary biopsies are taken and if it is safe to collect any extra biopsies.
• Benefits: Participants may not receive direct medical benefits, but the study will contribute to a better understanding of CVID and related conditions, potentially leading to improved treatments.

Conditions

XLA; CVID; Yao Syndrome; Blau Syndrome

Keywords

Blau Syndrome; XLA; Humoral Immunodeficiency; CVID enteropathy; CVID; Agammaglobulinemia; Inborn Errors of Immunity; Yao Syndrome

Outcome Measures

Primary Outcomes (3)

• Establish pattern/pace of disease process

  To establish the pattern and pace of change of disease (frequency, distribution, type and extent of infections, inflammatory lesions and abnormalities of immune function).

  At 1 year and ongoing

• Evaluation of organ dysfunction/damage resulting from immune abnormality

  To establish the extent of organ involvement (infection and/or inflammation) and organ damage or dysfunction resulting from the abnormality of immune function.

  Ongoing

• Characterization of immune abnormalities

  To characterize the physiologic, biochemical or genetic basis of theabnormality of immunity.

  Ongoing

Secondary Outcomes (3)

• Assess ability to participate in other studies

  ongoing

• Determine eligibility for other studies

  ongoing

• Establish baseline of pattern/pace of disease process before participating in therapeutic trials

  ongoing

Study Arms (1)

General Population

Physician referral required

Eligibility Criteria

• Age: 2 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

General population - Physician referral required

You may qualify if:

• Must have a verifiable diagnosis of common variable immune deficiency as defined by a decrease both in IgG and at least one other Ig isotype to below two standard deviations of normal control levels OR B-cell immunodeficiencies related to CVI (defined as selective IgA deficiency, selective IgG isotype deficiency, agammaglobulinemia, and hypogammaglobulinemia associated with Epstein-Barr virus infection), or hypogammaglobulinemia associated with other related inborn errors of immunity. This includes patients with a defined diagnosis of Blau or Yao Syndrome.
• Must be 2 years old or greater.
• Patients with repeated infections and suspected of having an inborn error of immunity.
• Patients must be referred by their primary medical care provider.
• On investigator s discretion, unaffected family members (mother, father, siblings, children, grandparents, aunts, uncles, and first cousins) may be asked for the provision of blood or buccal specimens for research purposes.
• Patients who are lactating, may be eligible and will only undergo tests and procedures, and/or receive medications for which data exists that proves that they are minimal risk to the child.
• Pregnant women will not be newly enrolled onto this protocol, however existing patients who become pregnant while on study will remain on study, as literature about pregnancy in CVI patients is sparse and outside providers have minimal knowledge about managing CVI during pregnancy. Pregnant women will only undergo tests and procedures, and/or receive medications for which data exists that proves that they are minimal risk to the fetus. Pregnant unaffected relatives will not be enrolled in this study).
• All patients must be willing to have research samples stored for future studies and/or other research purposes.
• NIH staff and family members of study team members may be enrolled in this study as this population may meet study criteria. Neither participation nor refusal to participate as a subject in the research will have an effect, either beneficial or adverse, on the participant s employment or position at the NIH. Every effort will be made to protect participant information, but such information may be available in medical records and may be available to authorized users outside of the study team in both an identifiable and unidentifiable manner. The NIH investigator will provide and request that the NIH staff member review the Frequently Asked Questions (FAQs) for Staff Who are Considering Participating in NIH Research and the Leavy Policy for NIH Employees Participating in NIH Medical Research Studies (NIH Policy Manual 2300-630-3).

You may not qualify if:

• Presence of other medical illnesses that would preclude individuals from undergoing routine diagnostic testing or testing for immunologic features of immunodeficiency.
• Presence of a condition or treatment, such as HIV, cytotoxic chemotherapy or malignancy, that in the investigator s opinion could interfere with evaluation of the condition under study.
• Pregnancy at the time of enrollment.
• Inability of an adult participant to provide informed consent for themselves (decisionally impaired adult).

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 Publications (3)

• Jaffe JS, Eisenstein E, Sneller MC, Strober W. T-cell abnormalities in common variable immunodeficiency. Pediatr Res. 1993 Jan;33(1 Suppl):S24-7; discussion S27-8. doi: 10.1203/00006450-199305001-00128.

  PMID: 7679486 BACKGROUND

• Mannon PJ, Fuss IJ, Dill S, Friend J, Groden C, Hornung R, Yang Z, Yi C, Quezado M, Brown M, Strober W. Excess IL-12 but not IL-23 accompanies the inflammatory bowel disease associated with common variable immunodeficiency. Gastroenterology. 2006 Sep;131(3):748-56. doi: 10.1053/j.gastro.2006.06.022.

  PMID: 16952544 BACKGROUND

• Cunningham-Rundles C. Autoimmune manifestations in common variable immunodeficiency. J Clin Immunol. 2008 May;28 Suppl 1(Suppl 1):S42-5. doi: 10.1007/s10875-008-9182-7. Epub 2008 Mar 6.

  PMID: 18322785 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Blau syndrome; Agammaglobulinemia

Condition Hierarchy (Ancestors)

Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Officials

• Warren Strober, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kimberly L Montgomery-Recht, R.N.

CONTACT

(240) 422-7966; kim.montgomery-recht@nih.gov

Study Design

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

Study Record Dates

• First Submitted: November 3, 1999
• First Posted: November 4, 1999
• Study Start: January 15, 1990
• Last Updated: April 20, 2026

Record last verified: 2026-04-14

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)