Metabolic Profiling of Immune Responses in Immune-mediated Diseases

  • STATUS
    Recruiting
  • End date
    Jun 30, 2027
  • participants needed
    200
  • sponsor
    National Institute of Allergy and Infectious Diseases (NIAID)
Updated on 22 July 2022
psoriasis
eczema
Accepts healthy volunteers

Summary

Background

The immune system is the part of the body that fights infection. Some people have immune deficiencies that cause skin rashes, make them get sick often with infections, or make it difficult for their skin to heal. Researchers want to learn more to better treat conditions that affect immune response.

Objective

To learn about how the immune system and skin healing are related to each other.

Eligibility

People ages 18-75 with primary immune deficiency, eczema, or psoriasis. Healthy volunteers are also needed.

Design

Participants will be screened with a medical and medicine history and a physical exam. They may take a pregnancy test.

Participants will discuss the medicines or supplements they take as well as skin products they use, such as soaps and lotions.

Participants will have up to 4 skin biopsies taken from the forearm. A needle will inject an anesthetic into the skin where the biopsy will be done. A sharp tool that looks like a tiny cookie cutter will be used to remove a round plug of skin a bit smaller than the tip of a pencil.

Participants will give at least 1 blood sample.

Participants may have optional skin swab collection. A cotton swab will be used to swab the skin on the arm.

Participants may have optional skin tape collection. A sticky strip of tape will be placed on the arm and then removed.

Participants may give leftover samples taken as part of their regular medical care.

Participation will last for about 4 days. Participants will have 2 visits that each last about 1 hour. They may be asked to repeat the study in the future.

Description

The primary objective of this research is to perform in vivo assessment of the metabolic signatures associated with immunity, with particular focus on the immune modulators of wound healing and tissue repair.

Perhaps the most demonstrative example of immune dysfunction resulting from metabolic disorder is that of adenosine deaminase (ADA) severe combined immune deficiency (SCID). While several other metabolic disruptions can also lead to SCID, ADA deficiency causes an intracellular accumulation of deoxyadenosine, which, among other actions, interferes with the VDJ rearrangement needed for proper lymphocyte function and contributes to cell apoptosis. Additional immune phenotypes have been described for monogenic or digenic disorders of glycerophospholipid metabolism, amino acid transport, glycosylation, and oxidative phosphorylation. Metabolic processes are also known to influence the function of T cells, dendritic cells, and macrophages. More recent work has also suggested that metabolic reprograming offers innate immune cells a form of memory, previously thought to be exclusive to the adaptive immune system.

In addition to metabolic signatures associated with immune defects, this protocol will provide insights into how these immune defects impact wound healing and tissue repair. Recent work from our group has suggested that metabolic imbalance downstream of STAT3 may drive both the reduced wound healing seen in patients with autosomal dominant hyperimmunoglobulin E syndrome (AD HIES) or atopic dermatitis as well as in keloid scarring disorder.

This sample collection protocol will enroll 50 to 150 adult participants who are healthy volunteers or patients with confirmed or suspected primary immunodeficiency, psoriasis, or atopic dermatitis. We will perform exploratory evaluations of metabolomics of immune mediated diseases in peripheral blood cells, serum, skin biopsies, skin tape strips, and skin swabs. We will contrast this host information with metabolomics of the microbiome as collected by RNA sequencing and mass spectrometry. Participants will have up to 4 skin punch biopsies from the forearm over the course of 4 days to capture wound healing progress and identify involved pathways. During the same timeframe, we will collect peripheral blood to assess the metabolic signature of immune cells and serum/plasma. This protocol will afford the ability to link known immune defects (monogenic or digenic immune disorders, atopic dermatitis, or psoriasis) with metabolic profiling. We will be able to link, within individual cell types, serum, and skin samples, how (as one example) mutations in STAT3 shift the metabolic responses. Ultimately, we expect to construct a searchable database directly linking immune pathways with their associated metabolic signatures in blood cells, serum, and skin.

We anticipate that the research will provide critical new information on the human skin immune and remodeling responses and will have direct relevance for the development of vaccines, diagnostics, and therapeutics. All research procedures will be performed at the National Institutes of Health Clinical Center.

Details
Condition Primary Immunodeficiency, Psoriasis, Atopic Dermatitis, Immune-mediated Diseases
Clinical Study IdentifierNCT04864886
SponsorNational Institute of Allergy and Infectious Diseases (NIAID)
Last Modified on22 July 2022

Eligibility

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If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

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Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

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