Modeling Host-Pathogen Interaction Using Lymphoid Organoids

Trial statusRecruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age2-120
SponsorNational Institute of Allergy and Infectious Diseases (NIAID)

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Aged >=2 yrs.

Undergoing tonsillectomy as part of their clinical care.

Able to provide informed consent (for ages >=18 years) or has a parent or guardian who can provide informed consent on their behalf (for ages <18 yrs).

Willing to allow samples and data to be stored and shared for future secondary research.

Disqualifiers

Active infection.

Active tonsilitis.

Pregnant.

Diagnosed with an immunosuppressive condition or currently taking immunosuppressive medications.

Trial population

Patients undergoing tonsillectomy as part of their clinical care at hospitals and pediatric ear nose and throat (ENT) practices in the US will be enrolled.

Trial design

Design model

Cohort

Time perspective

Prospective

Treatments tested in this trial

Not listed

Trial groups

500 Participants
are grouped into 1 trial group
Group A: Tonsillectomy Patients

Trial outcomes

Primary outcomes

1

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.

Time frame
At time of collection
2

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
3

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
4

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

Secondary outcomes

1

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
2

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
3

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
4

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

Other outcomes

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