Natural History of Intestinal Inflammation in People With Primary Immune Dysregulations

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

WITHDRAWN

Study Classification

OBSERVATIONAL

Study Start Date

2023-09-08

Study Completion Date

2023-09-08

Brief Summary

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Background:

PIDD stands for primary immune dysregulation. It is a general term that includes many different inherited immune system disorders. The immune system is the part of the body that helps fight disease and infection. People with PIDDs can develop many kinds of health problems. One of these is inflammatory bowel disease (IBD), which causes diarrhea and cramping. Researchers want to learn more about these disorders to develop possible treatments.

Objective:

To learn more about when and why IBD may develop in some people with PIDDs.

Eligibility:

People ages 3 and older who have PIDD or IBD.

Healthy volunteers in this age group are also needed.

Design:

Visit 1: Participants will be screened with physical exam, medical history, and blood and urine tests.

Visit 2: Participants will:

* Have more physical exams and blood and urine tests.
* Answer questions about quality of life and food history.
* Provide a stool sample.
* Have nasal and rectal skin swabs.
* Have saliva collected.

Participants will have 1 follow-up visit per year. They will repeat visit 2 procedures.

Participants will be contacted by phone or email in between yearly visits. They will be asked about their health. They will complete a quality-of-life questionnaire and send a stool sample that is collected at home.

If participants experience a sudden change in symptoms or undergo a new treatment, they may be asked to complete visit 2 procedures.

If participants are not able to come to NIH, study data and samples can be collected without an in-person visit.

Participants will have a final study visit about 10 years after Visit 1. They will repeat visit 2 procedures.

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Detailed Description

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Over 1 million people suffer from IBD in the United States. Although the exact pathogenesis is unclear, IBD results from an inappropriate inflammatory response to intestinal microbes which is influenced by the environment in a genetically susceptible host. IBDs can be classified as conventional (Crohn disease (CD) and ulcerative colitis (UC)) and unclassified (early onset, difficult to treat, associated with monogenic disorders and PIDDs). Among the 200 IBD susceptibility loci identified in genome-wide association studies (GWAS), overlap with aberrations identified in PIDDs has been observed, thereby supporting the study of PIDDs to better understand conventional IBD pathogenesis, while recognizing PIDD-associated IBDs as distinct disease entities requiring specialized management.

The prevalence of PIDDs worldwide is estimated at 1 in 2000 live births and encompasses a growing list of over 300 PIDDs. Despite the fact that GI disease is the second most common complication in patients with PIDDs (rates ranging from 5-50%), little is known about PIDDspecific

IBD pathogenesis and even less is understood about the role of the microbiota both as a consequence and modulator of immune response in these inherited disorders. Moreover, there may be a time-limited period ("immunological window of opportunity"), coinciding with the maturation of the host s microbiome, during which early immune education may have long-term effects on predisposition to aberrant immune responses and inflammatory dysregulation. The primary objective of this study is to determine if PIDDs result in intestinal dysbioses, which alter local and systemic immune responses. Our long-term goal is to comprehensively investigate the immunological window of opportunity as it relates to PIDD-associated IBDs to define time-sensitive immunoregulatory targets for therapeutic intervention. We will pursue this goal through a prospective, longitudinal study of pediatric and adult patients with PIDDs (with and without IBD) before and after treatment and/or diagnostic interventions, including but not limited to hematopoietic stem cell transplantation (HSCT). Findings from subjects with PIDDs will be compared to those from subjects with IBD as well as healthy volunteers. This multifaceted study will complement primary patient protocols while allowing for the direct interrogation of specific arms of innate and adaptive immunity in the context of host-microbiome interactions. Patients will be studied over time through the collection of clinical metadata, blood, stool, urine, saliva, skin swabs, and biopsies obtained from clinically-indicated endoscopies in age-appropriate patients. PIDDs of interest include but are not limited to: CGD, CTLA4 and LRBA protein deficiency, hypomorphic RAG deficiency, and IPEX syndrome.

Conditions

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Chronic Granulomatous Disease Inflammatory Bowel Disease

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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IBD

-Patients with IBD without a diagnosed PIDD.-First- or second-degree relatives of patients with a PIDD of interest who do not have a PIDD themselves, but have diagnosed or suspected IBD.

No interventions assigned to this group

Non-PIDD/non-IBD (healthy volunteers)

healthy volunteers

No interventions assigned to this group

PIDD

CGD cohort; IPEX syndrome cohort; CTLA4 haploinsufficiency cohort; LRBA deficiency and hypomorphic RAG deficiency cohorts

No interventions assigned to this group

Eligibility Criteria

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Inclusion Criteria

* Age greater than or equal to 3 years.
* Willing to allow storage of samples for future research.
* Willing to allow genetic testing of their samples.
* Negative urine or serum pregnancy test for women of childbearing potential.

* Enrollment as a patient with confirmed IBD in a current NIH protocol.
* Absence of clinical findings or history suggestive of a primary or acquired immunodeficiency (not including immunodeficiency caused by certain IBD treatments).

* Absence of clinical findings or history suggestive of a primary or acquired immunodeficiency.
* Absence of clinical findings or history suggestive of IBD.

Exclusion Criteria

* Active malignancy requiring treatment.
* HIV.
* Current treatment for hepatitis B.
* Current treatment for hepatitis C.
* Recreational IV drug use within the past 6 months (based on subject report).
* Participation in a research study of an investigational vaccine within the past 6 months.
* Any condition that, in the opinion of the investigator, contraindicates participation in this study.

* Treatment with systemic antimicrobials within the past 3 months, unless it is a prophylactic regimen consisting of either an azole , trimethoprim-sulfamethoxazole, a quinolone, or any antimicrobial regimen resembling a typical prophylaxis regimen used to treat a PIDD of interest.
* Treatment with immune modulators within the past 6 months.

Minimum Eligible Age

3 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes