Does collapse of immune privilege in the hair-follicle bulge play a role in the pathogenesis of primary cicatricial alopecia?

Background. The hair-follicle bulge has recently been added to a growing list of human tissue compartments that exhibit a complex combination of immunosuppressive mechanisms, termed immune privilege (IP), which seem to restrict immune-mediated injury in specific locations. As epithelial hair-follicle stem cells (eHFSC) reside in the hair-follicle bulge region, it is conceivable that these IP mechanisms protect this vital compartment from immune-mediated damage, thereby ensuring the ongoing growth and cyclic regeneration of the hair follicle. Primary cicatricial alopecias (PCA) are a group of inflammatory hair disorders that result in hair-follicle destruction and permanent alopecia. Growing evidence suggests that eHFSC destruction is a key factor in the permanent follicle loss seen in these conditions. Aim. To explore the possible role of bulge IP collapse in PCA pathogenesis. Methods. We report three clinically distinct cases of PCA. Immunohistochemical analyses of paired biopsies from lesional and uninvolved scalp skin were compared using recognized markers of IP. Results. Immunohistochemical investigation found increased expression of major histocompatibility complex (MHC) classes I and II and of β2-microglobulin in the bulge region of lesional follicles compared with uninvolved follicles in each case. Further, expression of the bulge marker keratin 15 was reduced in lesional skin in two of the cases. Conclusions. This small series represents our first preliminary attempts to ascertain whether bulge IP collapse may play a role in PCA pathogenesis. We present standard parameters relating to hair-follicle IP in the bulge region of three patients with distinct PCA variants, and show the presence of features consistent with bulge IP collapse in each case.