Staphylococcus Aureus in Atopic Dermatitis Immunopathology

Phase

N/A

Condition

Rash

Allergy

Dermatitis, Atopic

Treatment

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)

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

Clinical Study ID

NCT04715087

69HCL18_0732

2020-A01547-32

Ages > 18
All Genders
Accepts Healthy Volunteers

Study 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.

Eligibility Criteria

Inclusion

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 durationof 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 priorto 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 (exceptfeet)
With a sufficient extent to allow all the investigations
With a lesional area score ≥ 6

Exclusion

Exclusion Criteria:

Pregnancy or breast-feeding women, or planning to become pregnant or breastfeedduring 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 limbswithin 1 week before the inclusion visit
Subject treated with cyclosporine, methotrexate oral corticosteroids, azathioprine,mycophenolate-mofetil, and/or any other systemic immunosuppressor/immunomodulatorwithin 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 uncontrolleddespite treatment that is likely, in the opinion of the investigator, to impactpatient's ability to participate in the study or to impact the study efficacy orsafety 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 orprivate institution for a reason other than study, or incarcerated)
Subject in an exclusion period from a previous study or who is participating inanother clinical trial
Specific criteria for AD patients : o Subject currently experiencing or having a history of other concomitant skinconditions that would interfere with evaluation of AD
Specific criteria for healthy control :
Subject currently experiencing or having an history of AD or other concomitantcondition that would interfere with evaluation of skin reaction induced bypatch test

Study Design