Human Immunity Against Staphylococcus Aureus Skin Infection
Condition: Staphylococcus Aureus Skin Infection
MeSH terms: Infections; Communicable Diseases; Staphylococcal Infections; Cellulitis; Skin Diseases, Infectious; Staphylococcal Skin Infections
Study type: Interventional
Phase: Phase 1

Summary: 
      Background:

      - Staphylococcus aureus, or staph, is commonly found on the skin and in the respiratory
      system. Sometimes people who get sick with staph infection do not get better with standard
      treatment. These staph infections can be serious and even deadly. Researchers want to find
      out why some people are more likely to get the infection.

      Objectives:

      - To look at the immune response of the skin when it is exposed to bacteria.

      Eligibility:

        -  People age 2 65 with hyper IgE syndrome (HIES) and those with recurrent staph
           infections.

        -  Healthy volunteers.

      Design:

        -  Participants will be screened with medical history, physical exam, and blood tests.

        -  Over 1 5 days, participants may have blood tests and a skin and nasal swab. They may
           have additional tests if needed. If they had a recent biopsy, researchers may ask for a
           sample from it.

        -  Some participants will spend the night at the clinic. Their vital signs will be taken
           and they will have blood drawn. Some participants will take aspirin or ibuprofen
           starting 2 days before their stay.

        -  Some participants will have blisters created on the inside of their forearm. Suction
           will pull a layer of skin from their arm. Skin will be removed. Different solutions will
           be applied to the blisters. Up to 3 biopsies may be taken.

        -  Children will not have blood tests or biopsies.

        -  Participants will be called every day for 10 days, then at 30 days after the procedure.

        -  Participants will have a follow-up visit 10 days after the procedure.

        -  Participants who did not get blisters or biopsies will not have any follow-up
           appointments.
    

Detailed description: 
      The incidence of community-associated (CA) staphylococcal infections, especially those caused
      by methicillin-resistant Staphylococcus aureus (MRSA), has increased dramatically in recent
      years. Skin and soft tissues are the primary site for most of these infections, and skin or
      mucosal colonization increases the risk of disseminated disease. Many patients without
      apparent underlying immune dysfunction suffer from recurrent and persistent skin infections
      with MRSA. Additionally, patients with conditions such as atopic dermatitis and Hyper IgE (or
      Job s) Syndrome (HIES) are disproportionately affected. Although underlying host molecular
      defects responsible for some of these predisposing conditions have been uncovered in recent
      years (e.g. STAT3 mutations in HIES), the skin immune response to S. aureus infections has
      not been elucidated in either healthy controls or susceptible populations. In this protocol,
      we will perform exploratory evaluations of anti-staphylococcal immune responses in healthy
      subjects, subjects with STAT3 mutations, and otherwise healthy subjects with a history of
      recurrent staphylococcal skin infections. An additional group of subjects with other
      underlying conditions of interest may be included.

      The primary objective of this research is to perform in vivo and ex vivo challenges with
      killed bacteria through the use of the skin blister model and keratinocyte cultures to
      evaluate skin immune responses. Occasionally, a commensal fungi, such as Candida species may
      also be used. We will use three experimental approaches to complete this objective: 1)
      evaluation of in vivo responses in skin blisters to killed microbe exposure, 2) ex vivo
      evaluation of anti-microbial responses through derivation of keratinocyte cultures from skin
      blisters or biopsies, and 3) evaluation of function and immune-stimulatory ability of
      commensal organisms.

      Specifically, a suction blister device will be used to induce a skin blister on the forearm.
      The tops of the blisters will be removed, and solutions of killed S. aureus, commensal
      coagulase-negative staphylococcal species, or other Gram-negative commensals as well as
      commensal fungi, such as Candida species will be applied to the blisters to stimulate
      inflammatory responses. The blister fluid will then be collected at various time points over
      24 hours for laboratory analysis. Baseline skin and/or nasal swabs, skin biopsies, and blood
      draws will also be performed (The skin and nasal swabs may be performed at the screening or
      baseline visit.). Pediatric participants may be enrolled for baseline skin and/or nasal
      swabs. All research procedures will be performed at the National Institutes of Health
      Clinical Center. We anticipate that the research will provide critical new information on the
      human skin immune response to S. aureus that has direct relevance for the development of
      vaccines, diagnostics, and therapeutics.
    

Intervention name(s): S. aureus
Intervention type(s): Drug
Intervention description(s): S. aureus, commensal coagulase-negative staphylococcal species, and Gram-negative commensals, such as Roseomonas and Pseudomonas species
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: Skin Blister; Immune Response; Suction Device; Anti-Microbial; Killed Microbe