Longitudinal Immunophenotyping of Patients With Inflammatory Bowel Disease

Study Description:

This is a single-site, hypothesis-generating natural history study aiming to follow participants with inflammatory bowel disease. Participants will be followed long-term with a focus on immunophenotyping their conditions. Adult family members of participants will also be invited to enroll to provide blood samples for immune and genetic analyses.

Objectives:

Primary Objective: To collect longitudinal clinical data and specimens, with the goal of identifying novel biomarkers correlating with disease activity or response to therapy

Secondary Objectives:

• To identify the dynamic molecular and immunological changes associated with chronic GI inflammation and mechanisms of response to FDA approved (biologic and small molecule inhibitors) therapies for IBD
• To study the molecular genetics underlying chronic GI inflammation
• To longitudinally quantify and characterize the nutritional status, food components, and overall diet of patients with IBD

Endpoints:

Primary Endpoint:

• Longitudinal collection of clinical data, biospecimens, and disease assessments at 6-month intervals over at least 3 years

Secondary Endpoints:

1.A) Mean change over baseline of immune cell populations, cellular transcript and protein expression, and cytokine levels in peripheral blood and mucosal tissue across at least 3 study visits during a two-year period.

1.B) Assessment of disease activity (endoscopic evaluation, and histopathology) at each endoscopy and evaluation of progression of disease activity across at least 3 endoscopies during a two-year period. If a treatment is implemented, then disease activity will be assessed and compared over consecutive endoscopies.

• C) Identification of molecular patterns or immune signatures that correlate with disease activity and response to treatment
• A) Quantification of gene expression data and its trajectory over the course of disease and after therapy

2.B) Establishment of positive or negative correlation between candidate susceptible genes and disease phenotype

3.A) To establish positive or negative correlations between specific food components and nutrient amounts with disease activity obtained from questionnaires over 12 months

3.B) to establish correlations with nutritional data and the microbiome over 12 months

• INCLUSION CRITERIA

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

Affected Participant cohort:

• Adults 18 - 85 years of age
• History of:

• a verifiable diagnosis of Crohn's disease, ulcerative colitis, or IBD known to be associated with a co-existing condition (such as CTLA4 deficiency or common variable immune deficiency) and which is supported by characteristic clinical features, radiographic or endoscopic findings, or consistent histopathologic mucosal changes related to chronic inflammation; and/or
• a defined genetic syndrome/mutation linked to inflammatory bowel disease risk with or without symptoms or findings consistent with IBD
• Presence of a referring community physician who would be able to manage care outside of NIH

Unaffected family member of participant:

Immediate relative to the enrolled participant (mother, father, sibling, or adult child) may be recruited and enrolled to improve interpretation of genetic results or expand the phenotype of the IBD

• Adults 18 - 99 years of age
• In good general health
• No medical diagnosis of IBD

Exclusion criteria

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

• Unable or unwilling to provide informed consent
• Evidence of significant medical illnesses that the investigators feel may interfere with study evaluations and procedures