Comparative transcriptomic analyses of atopic dermatitis and psoriasis reveal shared neutrophilic inflammation

• Published in: Journal of allergy and clinical immunology Vol. 130; no. 6; pp. 1335 - 1343.e5
• Main Authors: Choy, David F., Hsu, Daniel K., Seshasayee, Dhaya, Fung, Maxwell A., Modrusan, Zora, Martin, Flavius, Liu, Fu-Tong, Arron, Joseph R.
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 01.12.2012; Elsevier; Elsevier Limited
• Subjects: Adult; Aged; Allergic diseases; Allergy and Immunology; Asthma; Atopic dermatitis; Biological and medical sciences; Blood; blood serum; Cell Movement; chemoattractants; Chemokines; Chemokines - genetics; Chemokines - metabolism; Chemotactic factors; Chronic illnesses; Cloning; Cytokines; Data processing; Dermatitis, Atopic - genetics; Dermatitis, Atopic - immunology; Dermatology; Disease; DNA microarrays; eosinophil; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Gene expression; gene expression microarray; genes; Growth factors; Helper cells; Humans; Hypersensitivity; Hypothesis testing; Immunoglobulin E; Immunoglobulin E - blood; immunohistochemistry; Immunopathology; Inflammation; Inflammation Mediators - metabolism; Inflammatory diseases; Leukocytes (eosinophilic); Leukocytes (neutrophilic); Lymphocytes T; Male; Medical sciences; Methods; Microarray Analysis; microarray technology; Microscopy; Middle Aged; neutrophil; neutrophils; Neutrophils - immunology; patients; Polarization; Psoriasis; Psoriasis - genetics; Psoriasis - immunology; Psoriasis. Parapsoriasis. Lichen; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Skin - immunology; Skin allergic diseases. Stinging insect allergies; Skin diseases; Th1-Th2 Balance; TH17; TH2; Transcriptome; transcriptomics; Young Adult; CCGf; DE; AD; AD-GS; H&E; C-GS; Ps-GS; GS; neutrophil; MPO; PCA; gene expression microarray; PC; Atopic dermatitis; FDR; psoriasis; eosinophil; TH17; SPCA; TH2; Cytokines, chemokines, and growth factors; T H17; T H2; Principal component; Supervised principal component analysis; Common lesional gene set; Myeloperoxidase; Differential expression; Hematoxylin and eosin; Gene set; Lesional atopic dermatitis gene set; False discovery rate; Principal component analysis; Lesional psoriasis gene set; Allergy; Immunopathology; Skin disease; Psoriasis; 17; Granulocyte; Inflammation; Gene expression; Eosinophil; Atopy; 2; Immunology; T; T-Lymphocyte; Th2 lymphocyte; Neutrophil; Th17 lymphocyte; Comparative study
• ISSN: 0091-6749; 1097-6825; 1097-6825
• DOI: 10.1016/j.jaci.2012.06.044

Atopic dermatitis (AD) and psoriasis are common inflammatory diseases canonically described as involving distinct TH polarization and granulocytic infiltration. Acute AD lesions are associated with TH2 and eosinophilic inflammation, whereas psoriatic lesions are associated with TH1/TH17 and neutrophilic inflammation. Despite intensive investigation, these pathways remain incompletely understood in vivo in human subjects. Using AD and psoriatic lesional skin as exemplar TH2 and TH1/TH17 diseased tissue, we sought to clarify common and unique molecular and pathophysiologic features in inflamed skin with different types of inflammatory polarization. We conducted gene expression microarray analyses to identify distinct and commonly dysregulated expression in AD (based on Hanifin and Rajka criteria) and psoriatic lesions. We defined gene sets (GSs) as comprising genes encoding cytokines, chemokines, and growth factors that were uniquely or jointly dysregulated in patients with AD and those with psoriasis and calculated aggregate GS expression scores for lesional skin of patients with these dermatoses and healthy control skin. The atopic dermatitis gene set (AD-GS) score correlated with systemic and local measures of allergic inflammation, including serum IgE levels, blood eosinophil counts, and tissue eosinophil counts. Unexpectedly, genes encoding neutrophil chemoattractants among the common GS were highly expressed in AD lesional skin. Hematoxylin and eosin and immunohistochemical analyses showed the numbers of neutrophils in AD lesional skin were comparable with those in psoriatic lesional skin, and both were correlated with the extent of expression of neutrophil chemoattractant genes. These data are evidence that neutrophilic inflammation is a feature of lesional AD pathology comorbid with allergic inflammation.