Trichohyalin is a potential major autoantigen in human alopecia areata.
Several lines of evidence support an autoimmune basis for alopecia areata (AA), a common putative autoimmune hair loss disorder. However, definitive support is lacking largely because the identity of hair follicle (HF) autoantigen(s) involved in its pathogenesis remains unknown. Here, we isolated AA-reactive HF-specific antigens from normal human scalp anagen HF extracts by immunoprecipitation using serum antibodies from 10 AA patients. Samples were analyzed by LC-MALDI-TOF/TOF mass spectrometry, which indicated strong reactivity to the hair growth phase-specific structural protein trichohyalin in all AA sera. Keratin 16 (K16) was also identified as another potential AA-relevant target HF antigen. Double immunofluorescence studies using AA (and control sera) together with a monoclonal antibody to trichohyalin revealed that AA sera contained immunoreactivity that colocalized with trichohyalin in the growth phase-specific inner root sheath of HF. Furthermore, a partial colocalization of AA serum reactivity with anti-K16 antibody was observed in the outer root sheath of the HF. In summary, this study supports the involvement of an immune response to anagen-specific HFs antigens in AA and specifically suggests that an immune response to trichohyalin and K16 may have a role in the pathogenesis of the enigmatic disorder.
Leung
Man Ching
MC
Centre for Skin Sciences, School of Life Sciences, University of Bradford, Bradford, West Yorkshire, United Kingdom.
Sutton
Chris W
CW
Fenton
David A
DA
Tobin
Desmond J
DJ
D000328:Adult; D000506:Alopecia Areata / Q000097:blood / Q000276:immunology*; D001324:Autoantigens / Q000032:analysis* / Q000097:blood; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D018859:Hair Follicle / Q000276:immunology / Q000473:pathology; D006801:Humans; D007381:Intermediate Filament Proteins; D053536:Keratin-16 / Q000032:analysis / Q000097:blood; D008297:Male; D011498:Protein Precursors / Q000032:analysis* / Q000097:blood; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D001324:Autoantigens; D007381:Intermediate Filament Proteins; D053536:Keratin-16; D011498:Protein Precursors; C016159:trichohyalin