Identification of Autoantigen Epitopes in Alopecia Areata.
Alopecia areata (AA) is believed to be a cell-mediated autoimmune hair loss disease. Both CD4 and cytotoxic CD8 T cells (CTLs) are important for the onset and progression of AA. Hair follicle (HF) keratinocyte and/or melanocyte antigen epitopes are suspected potential targets of autoreactive CTLs, but the specific epitopes have not yet been identified. We investigated the potential for a panel of known epitopes, expressed by HF keratinocytes and melanocytes, to induce activation of CTL populations in peripheral blood mononuclear cells. Specific synthetic epitopes derived from HF antigens trichohyalin and tyrosinase-related protein-2 induced significantly higher frequencies of response in AA CTLs compared with healthy controls (IFN-gamma secretion). Apoptosis assays revealed conditioned media from AA peripheral blood mononuclear cells stimulated with trichohyalin peptides elevated the expression of apoptosis markers in primary HF keratinocytes. A cytokine array revealed higher expression of IL-13 and chemokine ligand 5 (CCL5, RANTES) from AA peripheral blood mononuclear cells stimulated with trichohyalin peptides compared with controls. The data indicate that AA affected subjects present with an increased frequency of CTLs responsive to epitopes originating from keratinocytes and melanocytes; the activated CTLs secreted soluble factors that induced apoptosis in HF keratinocytes. Potentially, CTL response to self-antigen epitopes, particularly trichohyalin epitopes, could be a prognostic marker for human AA.
Department of Dermatology and Skin Science, University of British Columbia, Vancouver, British Columbia, Canada.
Eddy H C
EHC
Wang
Department of Dermatology and Skin Science, University of British Columbia, Vancouver, British Columbia, Canada.
Mei
M
Yu
Department of Dermatology and Skin Science, University of British Columbia, Vancouver, British Columbia, Canada.
Trisia
T
Breitkopf
Department of Dermatology and Skin Science, University of British Columbia, Vancouver, British Columbia, Canada.
Noushin
N
Akhoundsadegh
Department of Dermatology and Skin Science, University of British Columbia, Vancouver, British Columbia, Canada.
Xiaojie
X
Wang
Department of Dermatology and Skin Science, University of British Columbia, Vancouver, British Columbia, Canada.
Feng-Tao
FT
Shi
Department of Dermatology and Skin Science, University of British Columbia, Vancouver, British Columbia, Canada.
Gigi
G
Leung
Department of Dermatology and Skin Science, University of British Columbia, Vancouver, British Columbia, Canada; Department of Dermatology and Skin Science, Vancouver General Hospital, Vancouver, British Columbia, Canada.
Jan P
JP
Dutz
Department of Dermatology and Skin Science, Vancouver General Hospital, Vancouver, British Columbia, Canada.
Jerry
J
Shapiro
Department of Dermatology and Skin Science, University of British Columbia, Vancouver, British Columbia, Canada. Electronic address: kmcelwee@mail.ubc.ca.
Kevin J
KJ
McElwee
D000328:Adult; D000368:Aged; D000465:Algorithms; D000506:Alopecia Areata / Q000097:blood* / Q000276:immunology*; D017209:Apoptosis; D001324:Autoantigens / Q000276:immunology*; D017077:Culture Media, Conditioned / Q000737:chemistry; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology*; D005260:Female; D015789:HLA-A2 Antigen / Q000378:metabolism; D006239:Haplotypes; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007381:Intermediate Filament Proteins / Q000378:metabolism; D015603:Keratinocytes / Q000276:immunology / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008297:Male; D008544:Melanocytes / Q000276:immunology / Q000378:metabolism; D008875:Middle Aged; D011379:Prognosis; D055815:Young Adult
D001324:Autoantigens; D017077:Culture Media, Conditioned; D016207:Cytokines; D000939:Epitopes; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D007381:Intermediate Filament Proteins; C016159:trichohyalin; D007371:Interferon-gamma