TY - JOUR
T1 - Patients with Atopic Dermatitis Colonized with Staphylococcus aureus Have a Distinct Phenotype and Endotype
AU - Simpson, Eric L.
AU - Villarreal, Miguel
AU - Jepson, Brett
AU - Rafaels, Nick
AU - David, Gloria
AU - Hanifin, Jon
AU - Taylor, Patricia
AU - Boguniewicz, Mark
AU - Yoshida, Takeshi
AU - De Benedetto, Anna
AU - Barnes, Kathleen C.
AU - Leung, Donald Y.M.
AU - Beck, Lisa A.
N1 - Funding Information:
One AD phenotype under study by the Atopic Dermatitis Research Network, funded by the National Institute of Allergy and Infectious Diseases, is the population that is colonized with S. aureus on the skin surface. Although a number of acquired and/or genetic defects in epithelial or immune functions have been identified and are thought to explain the viral susceptibilities observed in AD patients ( Bussman et al., 2008; Gao et al., 2009; Gao et al., 2012; Howell et al., 2011; Leung et al., 2011; Shiohara et al., 2011 ), the underlying mechanisms associated with S. aureus colonization and infection remain poorly understood. Both skin barrier dysfunction and impaired innate and adaptive immune responses have been implicated as causes of this S. aureus susceptibility ( Kuo et al., 2013; Leung 2013; Nakatsuji et al., 2016 ). S. aureus, in turn, exacerbates AD via effects on innate immune pathways, T-cell activation, and barrier integrity ( Brauweiler et al., 2014; Broccardo et al., 2011; Kobayashi et al., 2015; Leung et al., 2017 ). The goal of this study was to more comprehensively evaluate the clinical features, biophysical characteristics of the skin barrier, and peripheral blood and serum biomarkers found in S. aureus-colonized versus non–S. aureus-colonized adult European American, non-Hispanic AD patients to test the hypothesis that there are unique phenotypic or endotypic features that associate with colonization. Understanding the endotypes and phenotypes of colonized patients may help identify patients at risk and generate the basis for rational approaches to modulating S. aureus colonization, preventing S. aureus infection, and reducing disease severity in AD.
Funding Information:
The authors acknowledge Marshall Plaut, National Institute of Allergy and Infections Diseases project scientist and reviewer; Catherine Philpot at Rho, Inc., for centralized study coordination; and the following study coordinators for their hard work in recruiting human participants for this study: at University of Rochester Medical Center, Jean Sauvain, Nelissa Perez-Nazario, and Diane Wang; at National Jewish Health, Patricia Taylor, Caroline Bronchick, Amy Hoeft, and Anais Sanchez; and at Oregon Health & Science University, Emma Hill, Danielle McClanahan, Allison Wong, Susan Tofte, and Tamar Hajar. This work was funded by the National Institutes of Health/National Institute of Allergy and Infectious Diseases Atopic Dermatitis Research Network grants U19AI117673 and UM2AI117870.
Funding Information:
This work was funded by the National Institutes of Health/National Institute of Allergy and Infectious Diseases Atopic Dermatitis Research Network grants U19AI117673 and UM2AI117870.
Publisher Copyright:
© 2018 The Authors
PY - 2018/10
Y1 - 2018/10
N2 - Patients with atopic dermatitis (AD) are commonly colonized with Staphylococcus aureus (AD S. aureus+), but what differentiates this group from noncolonized AD patients (AD S. aureus–) has not been well studied. To evaluate whether these two groups have unique phenotypic or endotypic features, we performed a multicenter, cross-sectional study enrolling AD S. aureus+ (n = 51) and AD S. aureus– (n = 45) participants defined by the presence or absence of S. aureus by routine culture techniques and nonatopic, noncolonized control individuals (NA S. aureus–) (n = 46). Filaggrin (FLG) genotypes were determined, and disease severity (Eczema Area and Severity Index, Rajka-Langeland Severity Score, Investigator's Global Assessment score, Numerical Rating Scale, and Dermatology Life Quality Index) was captured. Skin physiology was assessed (transepidermal water loss [TEWL], stratum corneum integrity, hydration, and pH), and serum biomarkers were also measured. We found that AD S. aureus+ patients had more severe disease based on all scoring systems except itch (Numerical Rating Scale), and they had higher levels of type 2 biomarkers (eosinophil count, tIgE, CCL17, and periostin). Additionally, AD S. aureus+ patients had significantly greater allergen sensitization (Phadiatop and tIgE), barrier dysfunction (TEWL and stratum corneum integrity), and serum lactate dehydrogenase (LDH) than both the AD S. aureus– and NA S. aureus– groups. FLG mutations did not associate with S. aureus+ colonization. In conclusion, adult patients with AD who are colonized on their skin with S. aureus have more severe disease, greater type 2 immune deviation, allergen sensitization, barrier disruption, and LDH level elevation than noncolonized patients with AD.
AB - Patients with atopic dermatitis (AD) are commonly colonized with Staphylococcus aureus (AD S. aureus+), but what differentiates this group from noncolonized AD patients (AD S. aureus–) has not been well studied. To evaluate whether these two groups have unique phenotypic or endotypic features, we performed a multicenter, cross-sectional study enrolling AD S. aureus+ (n = 51) and AD S. aureus– (n = 45) participants defined by the presence or absence of S. aureus by routine culture techniques and nonatopic, noncolonized control individuals (NA S. aureus–) (n = 46). Filaggrin (FLG) genotypes were determined, and disease severity (Eczema Area and Severity Index, Rajka-Langeland Severity Score, Investigator's Global Assessment score, Numerical Rating Scale, and Dermatology Life Quality Index) was captured. Skin physiology was assessed (transepidermal water loss [TEWL], stratum corneum integrity, hydration, and pH), and serum biomarkers were also measured. We found that AD S. aureus+ patients had more severe disease based on all scoring systems except itch (Numerical Rating Scale), and they had higher levels of type 2 biomarkers (eosinophil count, tIgE, CCL17, and periostin). Additionally, AD S. aureus+ patients had significantly greater allergen sensitization (Phadiatop and tIgE), barrier dysfunction (TEWL and stratum corneum integrity), and serum lactate dehydrogenase (LDH) than both the AD S. aureus– and NA S. aureus– groups. FLG mutations did not associate with S. aureus+ colonization. In conclusion, adult patients with AD who are colonized on their skin with S. aureus have more severe disease, greater type 2 immune deviation, allergen sensitization, barrier disruption, and LDH level elevation than noncolonized patients with AD.
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U2 - 10.1016/j.jid.2018.03.1517
DO - 10.1016/j.jid.2018.03.1517
M3 - Article
C2 - 29604251
AN - SCOPUS:85047400674
VL - 138
SP - 2224
EP - 2233
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
SN - 0022-202X
IS - 10
ER -