Trichohyalin is a potential major autoantigen in human alopecia areata

J Proteome Res. 2010 Oct 1;9(10):5153-63. doi: 10.1021/pr100422u.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alopecia Areata / blood
  • Alopecia Areata / immunology*
  • Autoantigens / analysis*
  • Autoantigens / blood
  • Female
  • Fluorescent Antibody Technique, Indirect
  • Hair Follicle / immunology
  • Hair Follicle / pathology
  • Humans
  • Intermediate Filament Proteins
  • Keratin-16 / analysis
  • Keratin-16 / blood
  • Male
  • Protein Precursors / analysis*
  • Protein Precursors / blood
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Substances

  • Autoantigens
  • Intermediate Filament Proteins
  • Keratin-16
  • Protein Precursors
  • trichohyalin