Transcriptional profiling in alopecia areata defines immune and cell cycle control related genes within disease-specific signatures.
Alopecia areata (AA) is a non-scarring inflammatory hair loss disease with a complex autoimmune etiopathogenesis that is poorly understood. In order to investigate the pathogenesis of AA at the molecular level, we examined the gene expression profiles in skin samples from lesional (n=10) and non-lesional sites (n=10) of AA patients using Affymetrix Hu95A-v2 arrays. 363 genes were found to be differentially expressed in AA skin compared to non-lesional skin; 97 were up-regulated and 266 were down-regulated. Functional classification of the differentially expressed genes (DEGs) provides evidence for T-cell mediated immune response (CCL5, CXCL10, CD27, ICAM2, ICAM3, IL7R, and CX3CL1), and a possible humoral mechanism (IGHG3, IGHM, and CXCR5) in AA. We also find modulation in gene expression favoring cellular proliferation arrest at various levels (FGF5, FGF18, EREG, and FOXC2) with apoptotic dysregulation (LCK, TNF, TRAF2, and SFN) and decreased expression of hair follicle structural proteins. Further analysis of patients with AAT (<1 year duration, n=4) and AAP (>1 year duration, n=6) of disease revealed 262 DEGs distinctly separating the 2 groups, indicating the existence of gene profiles unique to the initial and later stages of disease.
Subramanya
Raghunandan Dudda
RD
Center for Investigative Dermatology, Division of Dermatology and Cutaneous Sciences, College of Human Medicine, East Lansing, MI, USA.
Coda
Alvin B
AB
Sinha
Animesh A
AA
D000328:Adult; D000506:Alopecia Areata / Q000235:genetics* / Q000276:immunology; D017209:Apoptosis / Q000235:genetics; D002453:Cell Cycle / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular / Q000235:genetics*; D056724:Immunity, Humoral / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000378:metabolism* / Q000473:pathology