Limits...
Gene expression profiles in chronic idiopathic (spontaneous) urticaria.

Patel OP, Giorno RC, Dibbern DA, Andrews KY, Durairaj S, Dreskin SC - Allergy Rhinol (Providence) (2015)

Bottom Line: Lesions of CIU showed significant upregulation of 506 genes and reduced expression of 51 genes.Twelve independent canonical pathways with p ≤ 0.001 were identified (including intracellular kinase pathways (RAs-related nuclear protein [RAN] and Janus activated kinase/interferon), cytokine signaling pathways (IL-9, IL10, and IFN), a strong inflammatory response (interferon, IL-9, IL-10, inducible nitric oxide synthase and glucocorticoid pathways) and increased cell proliferation (RAN signaling, cell cycle control, and tRNA charging).This preliminary study describes a method to study gene activation in urticarial lesions and demonstrated a strong inflammatory response with a large variety of activated genes that are distinct from those reported with other dermatologic conditions.

View Article: PubMed Central - PubMed

Affiliation: 1Division of Allergy and Clinical Immunology, Departments of Medicine and Immunology, University of Colorado Denver, Aurora, Colorado, USA.

ABSTRACT

Background: The pathophysiology of chronic idiopathic (spontaneous) urticaria (CIU) is poorly understood.

Objective: We hypothesized that a study of gene expression in active lesions from patients with CIU would uncover unexpected associations.

Methods: We enrolled eight patients with CIU and six healthy controls, and obtained 4 mm punch biopsy specimens of active lesions and unaffected skin of patients with CIU and of skin from normal controls. Routine histologic evaluation was performed, RNA was isolated, and gene expression data were assessed. Due to technical reasons, the final evaluation included six samples of lesional skin, six samples of nonlesional skin, and five samples of normal skin.

Results: As expected, lesional skin had more inflammatory cells per high-powered field (mean ± SE, 96 ± 6) than did samples from nonlesional skin of the subjects with CIU (17 ± 2) (p < 0.01). Lesions of CIU showed significant upregulation of 506 genes and reduced expression of 51 genes. Those most upregulated were predominantly involved in cell adhesion (e.g., selectin E [SELE]), cell activation (e.g., CD69), and chemotaxis (e.g., CCL2). Twelve independent canonical pathways with p ≤ 0.001 were identified (including intracellular kinase pathways (RAs-related nuclear protein [RAN] and Janus activated kinase/interferon), cytokine signaling pathways (IL-9, IL10, and IFN), a strong inflammatory response (interferon, IL-9, IL-10, inducible nitric oxide synthase and glucocorticoid pathways) and increased cell proliferation (RAN signaling, cell cycle control, and tRNA charging).

Conclusions: This preliminary study describes a method to study gene activation in urticarial lesions and demonstrated a strong inflammatory response with a large variety of activated genes that are distinct from those reported with other dermatologic conditions.

No MeSH data available.


Related in: MedlinePlus

Principle component analysis of gene expression data. Urticarial lesions (red) and control skin biopsy specimens (blue) are represented in three-dimensional space based on the global gene expression patterns of each sample. Lesional and control biopsy specimens obtained from the same individual are connected by a line. The biopsy specimens from healthy controls are not associated with lines.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4541630&req=5

Figure 1: Principle component analysis of gene expression data. Urticarial lesions (red) and control skin biopsy specimens (blue) are represented in three-dimensional space based on the global gene expression patterns of each sample. Lesional and control biopsy specimens obtained from the same individual are connected by a line. The biopsy specimens from healthy controls are not associated with lines.

Mentions: Principle components analysis of gene expression data revealed distinct consistency among samples. In Fig. 1, the axes are arbitrary values that summarize the variability in these data points in each of three independent analyses and account for 18% (x-axis), 13% (y-axis), and 9% (z-axis) of the variability among the samples. Samples from lesional skin (Fig. 1, red spheres) grouped together and clustered on the graph in an area that is distinct compared with samples from the nonlesional skin of subjects with CIU (Fig. 1, blue spheres with lines that connect to matched samples from lesional skin) and from the skin of normal controls (Fig. 1, blue spheres without lines). Although the distribution of the control data indicated that the gene expression profiles from nonlesional skin may be somewhat different from that of skin from normal controls due to the limited sample size, the data from normal skin and from nonlesional skin of patients with CIU were not statistically different and were grouped together for the subsequent analysis.


Gene expression profiles in chronic idiopathic (spontaneous) urticaria.

Patel OP, Giorno RC, Dibbern DA, Andrews KY, Durairaj S, Dreskin SC - Allergy Rhinol (Providence) (2015)

Principle component analysis of gene expression data. Urticarial lesions (red) and control skin biopsy specimens (blue) are represented in three-dimensional space based on the global gene expression patterns of each sample. Lesional and control biopsy specimens obtained from the same individual are connected by a line. The biopsy specimens from healthy controls are not associated with lines.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4541630&req=5

Figure 1: Principle component analysis of gene expression data. Urticarial lesions (red) and control skin biopsy specimens (blue) are represented in three-dimensional space based on the global gene expression patterns of each sample. Lesional and control biopsy specimens obtained from the same individual are connected by a line. The biopsy specimens from healthy controls are not associated with lines.
Mentions: Principle components analysis of gene expression data revealed distinct consistency among samples. In Fig. 1, the axes are arbitrary values that summarize the variability in these data points in each of three independent analyses and account for 18% (x-axis), 13% (y-axis), and 9% (z-axis) of the variability among the samples. Samples from lesional skin (Fig. 1, red spheres) grouped together and clustered on the graph in an area that is distinct compared with samples from the nonlesional skin of subjects with CIU (Fig. 1, blue spheres with lines that connect to matched samples from lesional skin) and from the skin of normal controls (Fig. 1, blue spheres without lines). Although the distribution of the control data indicated that the gene expression profiles from nonlesional skin may be somewhat different from that of skin from normal controls due to the limited sample size, the data from normal skin and from nonlesional skin of patients with CIU were not statistically different and were grouped together for the subsequent analysis.

Bottom Line: Lesions of CIU showed significant upregulation of 506 genes and reduced expression of 51 genes.Twelve independent canonical pathways with p ≤ 0.001 were identified (including intracellular kinase pathways (RAs-related nuclear protein [RAN] and Janus activated kinase/interferon), cytokine signaling pathways (IL-9, IL10, and IFN), a strong inflammatory response (interferon, IL-9, IL-10, inducible nitric oxide synthase and glucocorticoid pathways) and increased cell proliferation (RAN signaling, cell cycle control, and tRNA charging).This preliminary study describes a method to study gene activation in urticarial lesions and demonstrated a strong inflammatory response with a large variety of activated genes that are distinct from those reported with other dermatologic conditions.

View Article: PubMed Central - PubMed

Affiliation: 1Division of Allergy and Clinical Immunology, Departments of Medicine and Immunology, University of Colorado Denver, Aurora, Colorado, USA.

ABSTRACT

Background: The pathophysiology of chronic idiopathic (spontaneous) urticaria (CIU) is poorly understood.

Objective: We hypothesized that a study of gene expression in active lesions from patients with CIU would uncover unexpected associations.

Methods: We enrolled eight patients with CIU and six healthy controls, and obtained 4 mm punch biopsy specimens of active lesions and unaffected skin of patients with CIU and of skin from normal controls. Routine histologic evaluation was performed, RNA was isolated, and gene expression data were assessed. Due to technical reasons, the final evaluation included six samples of lesional skin, six samples of nonlesional skin, and five samples of normal skin.

Results: As expected, lesional skin had more inflammatory cells per high-powered field (mean ± SE, 96 ± 6) than did samples from nonlesional skin of the subjects with CIU (17 ± 2) (p < 0.01). Lesions of CIU showed significant upregulation of 506 genes and reduced expression of 51 genes. Those most upregulated were predominantly involved in cell adhesion (e.g., selectin E [SELE]), cell activation (e.g., CD69), and chemotaxis (e.g., CCL2). Twelve independent canonical pathways with p ≤ 0.001 were identified (including intracellular kinase pathways (RAs-related nuclear protein [RAN] and Janus activated kinase/interferon), cytokine signaling pathways (IL-9, IL10, and IFN), a strong inflammatory response (interferon, IL-9, IL-10, inducible nitric oxide synthase and glucocorticoid pathways) and increased cell proliferation (RAN signaling, cell cycle control, and tRNA charging).

Conclusions: This preliminary study describes a method to study gene activation in urticarial lesions and demonstrated a strong inflammatory response with a large variety of activated genes that are distinct from those reported with other dermatologic conditions.

No MeSH data available.


Related in: MedlinePlus