Staphylococcus Aureus in Atopic Dermatitis Immunopathology

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.


Eligibility Criteria:
Inclusion Criteria:

* Subject over 18 years of age
* Subject able to read, understand and give documented informed consent
* Subject who gave written informed consent
* Subject willing and able to comply with the protocol requirements for the duration of the study
* Subjects with health insurance coverage according to local regulations
* For woman with childbearing potential;

  * Use of a highly effective method of birth control from at least 1 month prior to study enrollment until the last visit
  * Negative urine pregnancy test at inclusion visit
* Subject with I, II, III or IV skin phototype (according to Fitzpatrick scale)
* Subject accepting patch-tests and skin biopsies Specific criteria for AD patients
* Subject diagnosed with moderate-to-severe AD, defined as EASI ≥7 and DLQI ≥ 6
* Subject with AD involvement of ≥ 5% of Body Surface Area (BSA)
* Subject with at least one AD lesion:

  * Located either on upper extremities (except hands) or lower extremities (except feet)
  * With a sufficient extent to allow all the investigations
  * With a lesional area score ≥ 6

Exclusion Criteria:

* Pregnancy or breast-feeding women, or planning to become pregnant or breastfeed during the study
* History of allergic reaction to local anesthetic product
* History of wound healing disorders (e.g. hypertrophic scars, keloids)
* Subject with known active infection to HBV, HCV or HIV
* Subject with known blood dyscrasia
* Subject having applied topical immunomodulators, non-steroidal anti-inflammatory, corticoids, antihistamines, antibiotics or disinfectants on investigational limbs within 1 week before the inclusion visit
* Subject treated with cyclosporine, methotrexate oral corticosteroids, azathioprine, mycophenolate-mofetil, and/or any other systemic immunosuppressor/immunomodulator within 4 weeks before the study
* Subject treated by a biologic therapy within 3 months before the study
* Subject treated with ultraviolet therapy within 4 weeks before study
* Subject presenting clinically significant medical disease that is uncontrolled despite treatment that is likely, in the opinion of the investigator, to impact patient's ability to participate in the study or to impact the study efficacy or safety assessments
* Subject treated with an investigational drug within 8 weeks or within 5 half-lives (if known), whichever is longer, before the baseline visit
* Subject with immunocompromised people in its close circle
* Subject protect by the law (adult under guardianship, or hospitalized in a public or private institution for a reason other than study, or incarcerated)
* Subject in an exclusion period from a previous study or who is participating in another clinical trial
* Specific criteria for AD patients :

  o Subject currently experiencing or having a history of other concomitant skin conditions that would interfere with evaluation of AD
* Specific criteria for healthy control :

  * Subject currently experiencing or having an history of AD or other concomitant condition that would interfere with evaluation of skin reaction induced by patch test