Staphylococcus Aureus in Atopic Dermatitis Immunopathology

Summary

Atopic Dermatitis (AD) is a frequent inflammatory skin disease characterized by recurrent eczema. It associates genetic/epigenetic-induced alterations of epidermal barrier and type-2 inflammation/hypersensitivity, which may be triggered by different antigens that pass through the altered skin . Some studies have reported that environmental pathogens such as house dust mites are able to induce type-2 inflammation through particular activation of innate immunity .

Multiple staphylococcal strains are commonly found on the skin of AD patients. Interestingly, recent findings suggest that S. aureus may be a key factor of AD inflammation: (i) 90% of AD patients have S. aureus skin colonization on lesional skin , (ii) AD patients with S. aureus skin colonization have more increased type-2 inflammatory markers in comparison with AD patients without SA skin colonization , (iii) skin colonization by monoclonal S. aureus strains correlate with severe flares and (iv) S. aureus is detected in both epidermis and dermis during AD flares; In this study, our hypothesis is that S. aureus induces AD flares through a type 2 T cell-mediated hypersensitivity against S. aureus, involving innate and adaptive responses. Conversely, S. epidermidis, a commensal strain, has a protective effect against S. aureus dysbiosis. To this end, we will characterize, in the skin and the blood, the immune response induced by cutaneous application of : i) S. aureus isolated from patients with moderate-to-severe AD which will mimic the cutaneous dysbiosis occurring in the natural course of AD; ii) S. aureus toxins without bacteria to evaluate the skin response against those particular proteins; iii) a laboratory strain of S. epidermidis, a common well-tolerated skin commensal bacteria; iv) a mix of S. aureus and S. epidermidis to evaluate the regulatory effect of S. epidermidis on the S. aureus-induced AD inflammation.

Importantly, this characterization will be led in AD patients (with alterations of skin barrier), compared to healthy volunteers (without alterations of skin barrier), as controls.

Conditions

• Atopic Dermatitis

Interventions

OTHER

Blood sample (Day -42 to Day -28, Day 3),Skin swab sampling (Day -42 to Day -28, Day 0, Day 13) , patch test application (Day 0) , skin biopsies (Day 13)

A 50 mL blood sample will be collected in Lithium Heparin tubes (45 mL) and dry tube (5 mL), by venipuncture, at screening and Day 3. Bacteriological samples from AD patients will be performed by swabbing the skin at screening visit (Day -42 to Day -28). Each sample will be cultured in a RPMI/human serum AB medium and methi.R (methicillin Resistant) strains will be eliminated. Thus, only S. aureus methi.S (methicillin Sensitive) will be isolated to be re-applied (via patchtest) to AD patient. A well-characterized S. epidermidis lab strain will be also applied to AD patients. Patch tests containing S. aureus, S. epidermidis or a mix S. aureus/S. epidermidis will be applied on healed or improved area as defined by a lesional score ≤ 1 or a 2-point change from the baseline lesional score. Patch tests will be applied 48h and reading of the patch tests results and biopsies will be performed 72h after patch test application.

OTHER

Blood sample (Day 0 ,Day 3),Skin swab sampling (Day 0,Day 13), patch test application (Day 1), skin biopsies (Day 13)

A 50 mL blood sample will be collected in Lithium Heparin tubes (45 mL) and dry tube (5 mL), by venipuncture, at Day 0 and Day 3. Each bacteriological sample from AD patients performed by swabbing the skin at screening visit will be cultured in a RPMI/human serum AB medium and methi.R (methicillin Resistant) strains will be eliminated. Thus, only S. aureus methi.S (methicillin Sensitive) will be isolated to be applied (via patchtest) to a paired (age/sex) healthy volunteer. A well-characterized S. epidermidis lab strain will be also applied to healthy volunteers. Patch tests containing S. aureus, S. epidermidis or a mix S. aureus/S. epidermidis will be applied on healthy skin. Patch tests will be applied 48h and reading of the patch tests results and biopsies will be performed 72h after patch test application

Sponsors & Collaborators

• Hospices Civils de Lyon

  lead OTHER

Principal Investigators

• Audrey NOSBAUM, MD, PhD · Allergy and Clinical Immunology Department - Centre Hospitalier Lyon Sud

Study Design

Allocation

NON_RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2022-10-26

Primary Completion

2025-01-31

Completion

2025-01-31

Countries

• France

Study Locations