Centre for Skin Sciences, School of Life Sciences, University of Bradford, Bradford, West Yorkshire, United Kingdom.
J Proteome Res. 2010 Oct 1;9(10):5153-63. doi: 10.1021/pr100422u.
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.
有几条证据支持斑秃（AA）的自身免疫基础，这是一种常见的假定自身免疫性脱发疾病。然而，由于其发病机制中涉及的毛囊（HF）自身抗原的身份仍然未知，因此缺乏明确的支持。在这里，我们使用 10 名 AA 患者的血清抗体通过免疫沉淀从正常人头皮生长期 HF 提取物中分离出 AA 反应性 HF 特异性抗原。通过 LC-MALDI-TOF/TOF 质谱分析样品，所有 AA 血清均对生长期特异性结构蛋白毛角蛋白 16（K16）表现出强烈的反应性。角蛋白 16（K16）也被鉴定为另一种潜在的 AA 相关靶 HF 抗原。使用 AA（和对照血清）和抗毛角蛋白 16 单克隆抗体进行双重免疫荧光研究表明，AA 血清中含有与 HF 生长期特异性内根鞘中毛角蛋白 16 共定位的免疫反应性。此外，在 HF 的外根鞘中观察到 AA 血清反应性与抗 K16 抗体的部分共定位。总之，这项研究支持对生长期特定 HF 抗原的免疫反应参与 AA，并特别表明对毛角蛋白 16 和 K16 的免疫反应可能在这种神秘疾病的发病机制中起作用。
