Global expression profiling in atopic eczema reveals reciprocal expression of inflammatory and lipid genes.
BACKGROUND
Atopic eczema (AE) is a common chronic inflammatory skin disorder. In order to dissect the genetic background several linkage and genetic association studies have been performed. Yet very little is known about specific genes involved in this complex skin disease, and the underlying molecular mechanisms are not fully understood.


RESULTS
We used human DNA microarrays to identify a molecular picture of the programmed responses of the human genome to AE. The transcriptional program was analyzed in skin biopsy samples from lesional and patch-tested skin from AE patients sensitized to Malassezia sympodialis (M. sympodialis), and corresponding biopsies from healthy individuals. The most notable feature of the global gene-expression pattern observed in AE skin was a reciprocal expression of induced inflammatory genes and repressed lipid metabolism genes. The overall transcriptional response in M. sympodialis patch-tested AE skin was similar to the gene-expression signature identified in lesional AE skin. In the constellation of genes differentially expressed in AE skin compared to healthy control skin, we have identified several potential susceptibility genes that may play a critical role in the pathological condition of AE. Many of these genes, including genes with a role in immune responses, lipid homeostasis, and epidermal differentiation, are localized on chromosomal regions previously linked to AE.


CONCLUSIONS
Through genome-wide expression profiling, we were able to discover a distinct reciprocal expression pattern of induced inflammatory genes and repressed lipid metabolism genes in skin from AE patients. We found a significant enrichment of differentially expressed genes in AE with cytobands associated to the disease, and furthermore new chromosomal regions were found that could potentially guide future region-specific linkage mapping in AE. The full data set is available at http://microarray-pubs.stanford.edu/eczema.
Sääf
Annika M
AM
Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden. annika.saaf@ki.se
Tengvall-Linder
Maria
M
Chang
Howard Y
HY
Adler
Adam S
AS
Wahlgren
Carl-Fredrik
CF
Scheynius
Annika
A
Nordenskjöld
Magnus
M
Bradley
Maria
M
D000328:Adult; D016022:Case-Control Studies; D002874:Chromosome Mapping; D016000:Cluster Analysis; D003876:Dermatitis, Atopic / Q000235:genetics* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D015894:Genome, Human; D006801:Humans; D007107:Immune System / Q000378:metabolism; D007249:Inflammation / Q000235:genetics* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D050155:Lipogenesis / Q000235:genetics*; D008297:Male; D008954:Models, Biological; D020411:Oligonucleotide Array Sequence Analysis; D009928:Organ Specificity / Q000235:genetics / Q000276:immunology; D012867:Skin / Q000378:metabolism / Q000473:pathology; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
C106644:SOCS3 protein, human; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins