Alopecia areata (AA) is an autoimmune condition causing harm to hair follicles, resulting in hair loss. The degree and pattern of hair loss can vary. Subtypes of AA encompass alopecia totalis, marked by complete hair loss on the scalp, and alopecia universalis, which entails complete loss of body hair. Additional clinical manifestations comprise patchy AA, diffuse AA, AA reticularis, AA ophiasis, AA sisaipho, and perinevoid AA.

Overview of alopecia totalis and alopecia universalis.

In a study by Jabbari et al., differential gene expression patterns were identified between alopecia totalis and patchy phenotypes. Genes linked to cell-mediated cytotoxicity, including PRF1 and several granzymes, along with chemokine genes involved in immune cell movement, displayed increased expression. In contrast, genes related to hair keratin and development, such as DSMG4, FGF18, and GPRC5D, exhibited reduced expression. The distinct genes with altered expression successfully differentiated AA samples from normal samples through hierarchical clustering.

Figure 1. Clinical classifications of alopecia areata variants (adopted from doi: 10.1016/j.crimmu.2021.02.001) 

Genome-wide association studies (GWAS) have proposed that AA is a multifaceted polygenic disorder with connections to numerous genes governing components of both the adaptive and innate immune systems. Petukhova et al., conducted a GWAS involving 1,054 cases and 3,278 controls, identifying 139 single nucleotide polymorphisms significantly linked to AA. Associations were revealed with genomic regions housing several genes responsible for regulating the activation and proliferation of regulatory T cells, CTLA4, interleukin, IL-2 receptor A, Eos (IKZF4), as well as the human leukocyte antigen (HLA). Furthermore, associations were also noted in regions containing genes expressed within the hair follicle itself (PRDX5 and STX17). Examining these gene sets in more detail holds the potential to uncover distinctive biomarkers for AA.

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Further readings

1. Jabbari A, Cerise JE, Chen JC, Mackay-Wiggan J, Duvic M, Price V, Hordinsky M, Norris D, Clynes R, Christiano AM. Molecular signatures define alopecia areata subtypes and transcriptional biomarkers. EBioMedicine. 2016 May;7:240-7. 
2. Olayinka JJT, Richmond JM. Immunopathogenesis of alopecia areata. Curr Res Immunol. 2021 Feb 6;2:7-11. 
3. Petukhova L, Duvic M, Hordinsky M, Norris D, Price V, Shimomura Y, Kim H, Singh P, Lee A, Chen WV, Meyer KC, Paus R, Jahoda CA, Amos CI, Gregersen PK, Christiano AM. Genome-wide association study in alopecia areata implicates both innate and adaptive immunity. Nature. 2010 Jul 1;466(7302):113-7. 
4. Petukhova L, Christiano AM. Functional Interpretation of Genome-Wide Association Study Evidence in Alopecia Areata. J Invest Dermatol. 2016 Jan;136(1):314-317.