UBC Theses and Dissertations

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UBC Theses and Dissertations

The pathogenesis of alopecia areata Wang, Eddy Hsi Chun


The development of a hair loss disease, alopecia areata (AA), is believed to be associated with the initiation of an autoimmune response triggered by the activation of cytotoxic T-cells (CTLs) by unidentified autoantigen epitopes. The long-term sequelae of AA also have not received investigation beyond clinical observations. I hypothesized that CTLs in AA can be activated by autoantigen epitopes derived from hair follicle (HF) cells and activated CTLs may affect the viability of HF keratinocytes. Furthermore, I hypothesized the development of AA can have adverse effects on heart health and induce apoptosis of cardiomyocytes mediated in part by stress hormones. To test these hypotheses, I stimulated AA human peripheral blood mononuclear cells (PBMCs) and mouse LNCs with HF autoantigen epitope peptides. I showed that trichohyalin (TCHH) peptides induced higher frequencies of AA PBMC activation and led to keratinocyte apoptosis, while cytokeratin 16 (KRT16) peptides activate more AA mouse LNCs; both indicating the importance of keratinocyte autoantigens in AA pathogenesis. We showed that AA mice displayed significantly heavier hearts and collagen deposition in hearts compared to controls. Exposure of heart tissues to stress hormone adrenocorticotrophic hormone (ACTH) resulted in differential expression of interleukin-18 (Il18) genes and increased secretion of cardiac disease marker cardic troponin-I (cTnI). AA patients showed highest levels of cTnI compared to androgenetic alopecia (AGA) and no-hair-loss (NHL) groups. Culturing of cardiomyocytes with plasma from AA subjects with higher levels of cTnI also resulted in higher levels of apoptosis compared to cultures with plasma expressing low levels of cTnI; suggesting presence of harmful factors in the plasma. Additionally, to prove AA is a cell-mediated disease, we established a new mouse model of AA via injecting naïve C3H/HeJ mice with cultured LNCs isolated from spontaneously affected AA mice. In conclusion, AA pathogenesis is associated with higher frequencies of PBMC or LNC activation upon keratinocyte antigen epitope challenge and AA development resulted in changes in gene expression and heart morphology in mice and heart tissue remodeling markers in humans.

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