Digestive System Diseases

All Conditions

Neoplasms

Symptoms and General Pathology

Rare Diseases

Intestinal Diseases

Carcinoma

Carcinoma in Situ

Hyperplasia

Gastrointestinal Diseases

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Tufting Enteropathy

Children without intestinal epithelial dysplasia

blood samples and skin biopsies

Skin biopsies

Olivier Goulet, MD, PhD

This PHRC is centred on the intestinal epithelial dysplasia ( DEI) or " tufting enteropathy " or TE the clinical and histo-pathological descriptions of which are specified well to the digestive plan(shot).

The objectives of this PHRC are:

* the phenotypic analysis of the intestinal epithelial dysplasia by clinical and histo-pathological investigations.
* the identification of proteins involved at the intestinal level in the differentiation, the proliferation and the membership of the epithelial cells
* from the phenotypic study, a genetic analysis of type maps by homozygote on the whole genome partner in an approach guided by possible candidate genes
* the study of the genes, chosen according to their location, to their profile of expression, and to their function in touch with the pathogenic hypotheses

Characterization Phenotypic and Genetic Study of the Intestinal Epithelial Dysplasia or Tufting Enteropathy (TE)

Characterization Phenotypic and Genetic Study of the Intestinal Epithelial Dysplasia or TE

identification of different family of genes involved in intestinal dysplasia

Identification of different mutations involved in intestinal dysplasia

Assistance Publique - Hôpitaux de Paris

Blood and Lymph Conditions

Diseases and Abnormalities at or Before Birth

Immune System Diseases

Skin and Connective Tissue Diseases

Syndrome

Necrosis

Granulomatous Disease, Chronic

Blister

Phagocyte Bactericidal Dysfunction

Leukocyte Disorders

Hematologic Diseases

Genetic Diseases, X-Linked

Genetic Diseases, Inborn

Immunologic Deficiency Syndromes

Chronic Disease

Disease Attributes

Skin Diseases

Skin Diseases, Vesiculobullous

Pathological Conditions, Anatomical

Chronic Graft Versus Host Disease

Chronic Granulomatous Disease

Pharmaceutical Solutions

All Drugs and Chemicals

Blister induction involves creating 8 blisters on the forearm and removing the tops of the blisters for primary cell culture derivation. After blister induction, subjects may have an optional overnight admission to assess cell infiltration in response to autologous serum and/or sterile saline solution.

Blister induction

The skin biopsies will involve up to 4 biopsies: 2 initial punch biopsies 2 mm in diameter, followed by a punch biopsy 3 (plus or minus 1) and 7 (plus or minus 2) days later using a 3 mm punch to encompass the initial biopsy sites, capturing the tissue at 3 and 7 days of healing.

Skin Biopsies

Ashleigh A Sun

Ian A Myles, M.D.

For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)

Background:

The way the body heals and protects itself from getting sick is called the immune response. Some people with weak immune systems get sick often or get rashes and skin infections. Researchers want to find out how the immune system and skin problems are related so they can help these people.

Objective:

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

Eligibility:

People ages 18-65 with hyper IgE syndrome or Job syndrome or people ages 7-65 with chronic granulomatous disease. Healthy volunteers ages 18 65 are also needed.

Design:

Participants will be screened with:

Medical history

Physical exam

Possible urine tests

Participants will have 1 to 3 visits within about a week. Visits will include the following:

Participants will have a wells device strapped to the inside of the forearm. It will suction the skin and pull the top layer away to form 8 blisters. The skin over the blisters and the liquid inside will be collected.

Participants will have up to 4 skin biopsies. A sharp tool will remove a small plug of skin from the forearm.

Participants may have blood and urine tests.

The skin on participants skin will be rubbed with a cotton swab.

Some participants will have an overnight visit. They will have the blister device placed back on the arm. The wells will be lined up over the blister wounds. The wells will be filled with either saline or the participant s blood serum. The device will be covered and left on the arm for up to 24 hours. Doctors will periodically remove some liquid from the wells.

The incidence of community-associated (CA) staphylococcal infections, especially those caused by methicillin-resistant Staphylococcus aureus (MRSA), has increased in recent years. Skin and soft tissues are the primary sites for these infections. Although many patients without apparent underlying immune dysfunction suffer from recurrent and persistent skin infections with S.aureus, patients with conditions such as hyper immunoglobulin E syndrome (HIES, or Job s syndrome) and chronic granulomatous disease (CGD) are disproportionately affected. Although underlying host molecular defects responsible for some of these predisposing conditions have been uncovered in recent years, the skin immune response to S. aureus infections has not been elucidated in either healthy volunteers or susceptible populations. We hypothesize that the local skin response determines susceptibility to S. aureus skin infection.

In this sample collection protocol, we will perform exploratory evaluations of anti-staphylococcal immune responses in healthy volunteers, subjects with HIES, and subjects with CGD. Following screening and baseline procedures, including blood draw and skin swab, subjects will have the option to undergo blister induction, where a suction device will be used to induce skin blisters on the forearm. The tops of the blisters and blister fluid will be collected for research testing and storage for future research. An optional overnight inpatient stay may be performed to collect additional cellular infiltrates in response to autologous serum and/or sterile saline. Subjects may also have up to 4 skin punch biopsies from the forearm over the course of a week to capture wound healing progress and identify involved genes. All research procedures will be performed at the National Institutes of Health Clinical Center (NIH CC).

The primary objective of this research is to perform ex vivo assessment of wound healing pathways using a skin blister model and skin biopsies to obtain keratinocyte cultures and evaluate skin immune responses. We will use three experimental approaches: 1) ex vivo evaluation of anti-microbial responses and tissue remodeling through derivation of keratinocyte cultures from skin blisters and biopsies, 2) in vivo and ex vivo assessment of cellular response after blister induction using overnight exposure to autologous serum and/or sterile saline, and 3) evaluation of in vivo responses to skin biopsies. 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.

Skin Immunity Sample Collection Involving Blisters and Biopsies

Evaluate epithelial cell responses to cutaneous wounds and infections of keratinocytes and other cutaneous epithelial cells in patients with HIES or CGD and healthy volunteers.

Identify cellular mediators that contribute to the inflammatory processthrough evaluation of infiltrating cell types.

Determine whether there are abnormalities in specific tissue repair pathways, such as epithelial to mesenchymal transition (EMT).

National Institute of Allergy and Infectious Diseases (NIAID)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Characterization Phenotypic and Genetic Study of the Intestinal Epithelial Dysplasia or Tufting Enteropathy (TE)	NCT01114035	Intestinal Epit... Tufting Enterop...	blood samples a... Skin biopsies	- 15 Years	Assistance Publique - Hôpitaux de Paris
Skin Immunity Sample Collection Involving Blisters and Biopsies	NCT03921515	Hyper-Immunoglo... Chronic Granulo...	Blister inducti... Skin Biopsies	7 Years - 65 Years	National Institutes of Health Clinical Center (CC)
Characterization Phenotypic and Genetic Study of the Intestinal Epithelial Dysplasia or Tufting Enteropathy (TE)	NCT01114035	Intestinal Epit... Tufting Enterop...	blood samples a... Skin biopsies	- 15 Years	Assistance Publique - Hôpitaux de Paris

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