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Alopecia areata profiling shows TH1, TH2, and IL-23 cytokine activation without parallel TH17/TH22 skewing

Published:August 24, 2015DOI:https://doi.org/10.1016/j.jaci.2015.06.032

      Background

      Alopecia areata (AA) is a common T cell–mediated disorder with limited therapeutics. A molecular profile of cytokine pathways in AA tissues is lacking. Although studies have focused on TH1/IFN-γ responses, several observations support a shared genetic background between AA and atopy.

      Objective

      We sought to define the AA scalp transcriptome and associated biomarkers with comparisons with atopic dermatitis (AD) and psoriasis.

      Methods

      We performed microarray and RT-PCR profiling of 27 lesional and 17 nonlesional scalp samples from patients with AA for comparison with normal scalp samples (n = 6). AA gene expression was also compared with samples from patients with lesional or nonlesional AD and those with psoriasis. A fold change of greater than 1.5 and a false discovery rate of less than 0.05 were used for differentially expressed genes (DEGs).

      Results

      We established the AA transcriptomes (lesional vs nonlesional: 734 DEGs [297 upregulated and 437 downregulated]; lesional vs normal: 4230 DEGs [1980 upregulated and 2250 downregulated]), including many upregulated immune and downregulated hair keratin genes. Equally impressive as upregulation in TH1/interferon markers (IFNG and CXCL10/CXCL9) were those noted in TH2 (IL13, CCL18, CCL26, thymic stromal lymphopoietin, and periostin), TH9/IL-9, IL-23 (p40 and p19), and IL-16 mediators (all P < .05). There were no increases in TH17/TH22 markers. Hair keratin (KRT) expressions (ie, KRT86 and KRT85) were significantly suppressed in lesional skin. Greater scalp involvement (>25%) was associated with greater immune and keratin dysregulation and larger abnormalities in nonlesional scalp samples (ie, CXCL10 and KRT85).

      Conclusions

      Our data associate the AA signature with TH2, TH1, IL-23, and IL-9/TH9 cytokine activation, suggesting consideration of anti-TH2, anti-TH1, and anti–IL-23 targeting strategies. Similar to psoriasis and AD, clinical trials with selective antagonists are required to dissect key pathogenic pathways.

      Key words

      Abbreviations used:

      AA (Alopecia areata), AD (Atopic dermatitis), AT (Alopecia totalis), AU (Alopecia universalis), DC (Dendritic cell), DEG (Differentially expressed gene), FCH (Fold change), HI (High inflammatory), ITGAX (Integrin, alpha X), JAK (Janus kinase), KRT (Keratin), KRTAP (Keratin-associated protein), MI (Moderate inflammatory), PDE4 (Phosphodiesterase 4), POSTN (Periostin), STAT1 (Signal transducer and activator of transcription 1), TSLP (Thymic stromal lymphopoietin)
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