Peripheral blood gene expression in alopecia areata reveals molecular pathways distinguishing heritability, disease and severity
| Autor: | Kristina Seiffert-Sinha, V Qafalijaj Hysa, Alvin B. Coda, Animesh A. Sinha |
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| Rok vydání: | 2010 |
| Předmět: |
Adult
Male Alopecia Areata Immunology Gene Expression Biology Pathogenesis Immune system Gene expression Genetics medicine Humans Gene Genetics (clinical) Aged Oligonucleotide Array Sequence Analysis Wnt signaling pathway Middle Aged Alopecia areata medicine.disease Killer Cells Natural Case-Control Studies Alopecia universalis Female Signal transduction Signal Transduction |
| Zdroj: | Genes & Immunity. 11:531-541 |
| ISSN: | 1476-5470 1466-4879 |
| DOI: | 10.1038/gene.2010.32 |
| Popis: | Alopecia areata (AA) is an autoimmune hair loss disorder in which systemic disturbances have been described, but are poorly understood. To evaluate disease mechanisms, we examined gene expression in the blood of defined clinical subgroups (patchy AA persistent type, AAP, n=5; alopecia universalis, AU, n=4) and healthy controls (unaffected relatives, UaR, n=5; unaffected non-relatives, UaNR, n=4) using microarrays. Unsupervised hierarchical clustering separates all four patient and control groups, producing three distinct expression patterns reflective of 'inheritance', 'disease' and 'severity' signatures. Functional classification of differentially expressed genes (DEGs) comparing disease (AAP, AU) vs normal (UaR) groups reveals upregulation in immune response, cytokine signaling, signal transduction, cell cycle, proteolysis and cell adhesion-related genes. Pathway analysis further reveals the activation of several genes related to natural killer-cell cytotoxicity, apoptosis, mitogen activated protein kinase, Wnt signaling and B- and T-cell receptor signaling in AA patients. Finally, 35 genes differentially expressed in AA blood overlap with DEGs previously identified in AA skin lesions. Our results implicate innate and adaptive immune processes while also revealing novel pathways, such as Wnt signaling and apoptosis, relevant to AA pathogenesis. Our data suggest that peripheral blood expression profiles of AA patients likely carry new biomarkers associated with disease susceptibility and expression. |
| Databáze: | OpenAIRE |
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