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.
STUDY DESCRIPTION: The purpose of this study is to collect tonsil tissues that are routinely discarded after tonsillectomy procedures to develop lymphoid organoid models to evaluate host-pathogen interactions in human health and disease. One such interaction is the human immunotolerance mechanism to the Chemotaxis Inhibitory Protein of S. aureus (CHIPS). OBJECTIVES: Primary Objectives: -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. Secondary Objective: -Modulate anti-CHIPS IgG4 class switching through variation of primary and costimulatory signals. ENDPOINTS: Primary Endpoints: Differences between the following within the "antigenic sin" contexts of re-exposure, and with repeated exposures to CHIPS: * Immune cell composition. * Anti-CHIPS antibody levels, including total and subclasses of IgG and their neutralizing capacity. * Cytokine levels. * Activation-induced cytidine deaminase (AID) levels. * Single-cell inference of class switch recombination (sciCSR). Secondary Endpoints: Differences between the following modulation of primary and costimulatory signals: * Immune cell composition. * Anti-CHIPS antibody levels, including total and subclasses of IgG and their neutralizing capacity. * Cytokine levels. * AID levels. * sciCSR
Study Type
OBSERVATIONAL
Enrollment
500
National Institute of Allergy and Infectious Diseases (NIAID)
Bethesda, Maryland, United States
RECRUITINGNational Institutes of Health Clinical Center
Bethesda, Maryland, United States
RECRUITINGImmune 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: At time of collection
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: At time of collection
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