Modeling Host-Pathogen Interaction Using Lymphoid Organoids
NCT Number: NCT06479837
Status: RECRUITING
Study Type: OBSERVATIONAL
Conditions: Staphylococcal Infections
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sex: ALL
Age: CHILD, ADULT, OLDER_ADULT
Enrollment: 500
Study Design: Observational Model: |Time Perspective: p
Start Date: 2024-09-10
Completion Date: 2044-12-01
Locations: National Institute of Allergy and Infectious Diseases (NIAID), Bethesda, Maryland, 20892, United States|National Institutes of Health Clinical Center, Bethesda, Maryland, 20892, United States

Summary:
Background:

Staphylococcus aureus (S. aureus) are bacteria that can make people sick. Sometimes, an S. aureus infection can develop inside the spine; these infections can lead to paralysis and death. Researchers do not know how S. aureus interacts with a person s cells to cause infections in the spine.

Objective:

To learn how S. aureus interacts with cells in the body using tissues from tonsils discarded after standard surgery to remove them.

Eligibility:

People aged 2 years and older who are scheduled to have their tonsils removed.

Design:

Researchers will select participants for the study based on review of their existing medical records, including results of blood tests; any imaging scans, including x-rays; and reports about tissue specimens.

Participants will answer questionnaires about their health and past infections. They can do this online or on paper.

Participants will collect a nasal swab 1 week before their surgery. They will be given a tool that looks like a long cotton swab. They will twirl it around inside their nose. The swab will pick up cells and fluids that will be used for research.

After their surgery, the participant s surgeon will save samples of tonsil tissue. The surgeon will send these tissue samples and the nasal swab to researchers at the NIH.

These tissues and the swab will be used in studies to help researchers understand how S. aureus interacts with cells in the body. They hope these studies will help them find better ways to treat S. aureus infections.

Primary Outcome Measures: Immune cell composition, Develop a lymphoid organoid model from discarded human tonsils and determine and compare the human immunologic signatures of primary exposure, within the "antigenic sin" contexts of re-exposure, and with repeated exposures to CHIPS., At time of collection|Anti-CHIPS antibody levels, including total and subclasses of IgG and their neutralizing capacity, Develop a lymphoid organoid model from discarded human tonsils and determine and compare the human immunologic signatures of primary exposure, within the "antigenic sin" contexts of re-exposure, and with repeated exposures to CHIPS., At time of collection|Cytokine levels, Develop a lymphoid organoid model from discarded human tonsils and determine and compare the human immunologic signatures of primary exposure, within the "antigenic sin" contexts of re-exposure, and with repeated exposures to CHIPS., At time of collection|Activation-induced cytidine deaminase (AID) levels, Develop a lymphoid organoid model from discarded human tonsils and determine and compare the human immunologic signatures of primary exposure, within the "antigenic sin" contexts of re-exposure, and with repeated exposures to CHIPS., At time of collection|Single-cell inference of class switch recombination (sciCSR), Develop a lymphoid organoid model from discarded human tonsils and determine and compare the human immunologic signatures of primary exposure, within the "antigenic sin" contexts of re-exposure, and with repeated exposures to CHIPS., At time of collection
Secondary Outcome Measures: Immune cell composition, Primary signals such as antigen characteristics, and secondary signals such as cytokines have been implicated in class switching to IgG4 but have not been defined with respect to CHIPS. Varying these signals and evaluating: 1) organoid immune cell composition, 2) antibody and 3) cytokines levels, and indicators of class switching such as 4) AID and 5) sciCSR levels, will enable us to evaluate modulation of human immunotolerance to CHIPS., At time of collection|Anti-CHIPS antibody levels, including total and subclasses of IgG and their neutralizing capacity, Primary signals such as antigen characteristics, and secondary signals such as cytokines have been implicated in class switching to IgG4 but have not been defined with respect to CHIPS. Varying these signals and evaluating: 1) organoid immune cell composition, 2) antibody and 3) cytokines levels, and indicators of class switching such as 4) AID and 5) sciCSR levels, will enable us to evaluate modulation of human immunotolerance to CHIPS., At time of collection|Cytokine levels, Primary signals such as antigen characteristics, and secondary signals such as cytokines have been implicated in class switching to IgG4 but have not been defined with respect to CHIPS. Varying these signals and evaluating: 1) organoid immune cell composition, 2) antibody and 3) cytokines levels, and indicators of class switching such as 4) AID and 5) sciCSR levels, will enable us to evaluate modulation of human immunotolerance to CHIPS., At time of collection|Activation-induced cytidine deaminase (AID) levels, Primary signals such as antigen characteristics, and secondary signals such as cytokines have been implicated in class switching to IgG4 but have not been defined with respect to CHIPS. Varying these signals and evaluating: 1) organoid immune cell composition, 2) antibody and 3) cytokines levels, and indicators of class switching such as 4) AID and 5) sciCSR levels, will enable us to evaluate modulation of human immunotolerance to CHIPS., At time of collection|Single-cell inference of class switch recombination (sciCSR), Primary signals such as antigen characteristics, and secondary signals such as cytokines have been implicated in class switching to IgG4 but have not been defined with respect to CHIPS. Varying these signals and evaluating: 1) organoid immune cell composition, 2) antibody and 3) cytokines levels, and indicators of class switching such as 4) AID and 5) sciCSR levels, will enable us to evaluate modulation of human immunotolerance to CHIPS., At time of collection