Broad defects in epidermal cornification in atopic dermatitis identified through genomic analysis

Genomic expression differences between AD and psoriasis (PS) compared with normal skin. Heat maps representing the top 25 upregulated (A) and downregulated (B) genes in PS and top 25 upregulated (C) and downregulated (D) genes in AD. FC values represent AD and PS versus normal skin; FDR <0.001.

Genomic expression differences between AD and psoriasis (PS) compared with normal skin. Heat maps representing the top 25 upregulated (A) and downregulated (B) genes in PS and top 25 upregulated (C) and downregulated (D) genes in AD. FC values represent AD and PS versus normal skin; FDR <0.001.

Genomic expression of terminal differentiation (CE and EDC) genes. A, Downregulation of terminal differentiation genes in AD compared with normal and psoriasis (PS) skin. FC by microarrays in log2 scale, ^∗FDR <0.05. B, Real-time PCR analysis showing significant downregulation of LCE1, LCE2, CDSN, and SPRR2C in AD; ^∗P <.05; ^∗∗P <.01; ^∗∗∗P <.001. C, Terminal differentiation class prediction, discriminating AD and PS. Horizontal bars represent centroids for the AD and PS groups (upregulated genes [vs normal] on the right and downregulated on the left). Norm, Normal.

Genomic expression of terminal differentiation (CE and EDC) genes. A, Downregulation of terminal differentiation genes in AD compared with normal and psoriasis (PS) skin. FC by microarrays in log2 scale, ^∗FDR <0.05. B, Real-time PCR analysis showing significant downregulation of LCE1, LCE2, CDSN, and SPRR2C in AD; ^∗P <.05; ^∗∗P <.01; ^∗∗∗P <.001. C, Terminal differentiation class prediction, discriminating AD and PS. Horizontal bars represent centroids for the AD and PS groups (upregulated genes [vs normal] on the right and downregulated on the left). Norm, Normal.

Compromised epidermal barrier integrity in AD versus normal skin. SC of a healthy volunteer (A and E) and a representative patient with AD patient (B-D, F). Nile red fluorescence in normal (G) and AD SC (H). CE (white arrows), corneodesmosomes (black arrows), lamellar body (white asterisk), and keratin filaments (white triangles). Disruption of CE, degradion of corneodesmosomes (B-D), increased corneocyte thickness, and decreased compaction of keratin filaments in AD (F) compared with normal skin (E). Decreased corneocyte compaction and reduced intercellular lipids in AD (H) versus normal skin (G). Scale bars: A-D, 500 nm; E and F, 5 um; G and H, × 40 magnification, zoom × 9.7.

Characterization of major terminal differentiation proteins in normal skin, psoriasis (PS), and AD by immunohistochemistry. Skin sections were stained for hyperplasia (K16) (A) and the following: FLG (B), IVL (C), CDSN (D), and LOR (E). Although PS and AD showed similar acanthosis (A), delayed expression and abnormal formation of differentiation proteins characterized AD.

Differentially and commonly upregulated (red) and downregulated (green) regulated genes in AD and psoriasis (PS) versus normal skin, by arrays. Overall many more genes were upregulated and downregulated in psoriasis than in AD, with 322 and 441 genes commonly upregulated and downregulated, respectively, in both diseases. Criteria of FC ≥3 and FDR <0.05 applied.

Genomic expression similarities between AD and psoriasis (PS) compared with normal skin. Heat maps representing the top 25 upregulated genes (A) and downregulated genes (B) in both AD and PS compared with normal skin. FC values represent AD and PS versus normal skin. All FDR values were highly significant (P < .001).

Genomic expression differences of T_H1, T_H2, and T_H17 immune pathways in AD, psoriasis (PS), and normal skin by microarray (A) and real-time PCR (B). Whereas PS deviates toward T_H1/T_H17, AD polarizes toward T_H2. C, “Immune-signature” class prediction classifying these diseases. Horizontal bars represent centroids for AD and PS groups (upregulated genes (vs normal) on the right, downregulated on the left). Norm, Normal.

Genomic expression differences of T_H1, T_H2, and T_H17 immune pathways in AD, psoriasis (PS), and normal skin by microarray (A) and real-time PCR (B). Whereas PS deviates toward T_H1/T_H17, AD polarizes toward T_H2. C, “Immune-signature” class prediction classifying these diseases. Horizontal bars represent centroids for AD and PS groups (upregulated genes (vs normal) on the right, downregulated on the left). Norm, Normal.