Major Histocompatibility Complex Class I Chain-Related Gene A Polymorphisms and Extended Haplotypes Are Associated with Familial Alopecia Areata

Abstract

Alopecia areata (AA) is characterized by hair loss in patches and may progress to total loss of scalp hair, or total loss of scalp and body hair. The major histocompatibility complex (HLA) is associated with susceptibility to AA, as well as other autoimmune diseases. In addition to HLA molecules, non-HLA molecules including the major histocompatibility complex class I chain-related gene A (MICA), a stress-inducible antigen, are also associated with several autoimmune diseases. To investigate associations between AA and the HLA loci, two genes and eight microsatellite markers spanning the HLA region were genotyped. MICA(*)6 was significantly associated with all phenotypes of AA (P=0.0083), whereas MICA(*)5.1 was significantly associated with patchy AA (P=0.029). Extended haplotype analysis shows the significant associations of haplotypes HLA-DQ1-DR6-MICA(*)5.1 (P=0.004) and HLA-DQB1*0201-DR3-MICA(*)5.1 (P=0.009) with AA. These results suggest that MICA is both a potential candidate gene and part of an extended HLA haplotype that may contribute to susceptibility to and severity of AA.

Vitamin D Deficiency in Mycosis Fungoides and Sézary Syndrome Patients Is Similar to Other Cancer Patients

“…[24][25][26] Of interest, low vitamin D levels were recently found in 90.7% of patients with alopecia areata, which is another T-cell mediated autoimmune disease with HLA-DR and HLA-DQB1 associations the same as MF and SS. [27][28][29][30] It was unexpected to find a difference in correction rate based on the type of vitamin D oral supplement. Individuals treated with 1000 IU of oral vitamin D3 were less likely to achieve normal serum levels than those treated with 50,000 IU of vitamin D2 twice a week.…”

Heat treatment increases the incidence of alopecia areata in the C3H/HeJ mouse model

“…However, the altered HPA activity was likely a consequence of the immune response associated with AA. In this study, the increased incidence of AA in 8-month-old (Barahmani et al 2006), and it was identified as a potential candidate gene and part of an extended HLA haplotype that may contribute to susceptibility of AA in humans (Barahmani et al 2006). MICA is expressed on the surface of epithelial cells of the gastric and intestinal mucosa (Stephens 2001), endothelial cells, fibroblasts, monocytes (Zwirner et al 1999), and keratinocytes within the epidermis and hair follicles (Tay et al 2000).…”

The Role of Hair Follicle Immune Privilege Collapse in Alopecia Areata: Status and Perspectives

“…NK, NKT, and some CD8 þ T cells) as well as NKG2D-activating ligands from the MICA (MHC I-related chain A) family may also have a key role in AA pathogenesis (Ito et al, 2008a, b;Petukhova et al, 2010). This is supported by genotyping (Barahmani et al, 2006) and genome-wide association study evidence (Petukhova et al, 2010;Jagielska et al, 2012). Interestingly, the injection of peripheral blood mononuclear cells from healthy individuals that were enriched for NKG2D þ or CD56 þ cells and activated by IL-2 into healthy human scalp skin transplanted onto severecombined immunodeficient mice can induce a hair loss pattern that copies the human AA phenotype (Gilhar et al, 2013).…”