Parafollicular bulges, but not hair bulb keratinocytes, are attacked in graft-versus-host disease of human skin.

Graft-versus-host disease (GVHD) has been shown to preferentially attack epithelial stem cell regions in the rete ridge of epidermis, the parafollicular bulge stem cells of the hair follicle, the limbus of the eye, the basal cells of filiform papilla of the tongue and the stem cell regions of gut crypts. The parafollicular bulge, but not the papillary bulb tip, has recently been shown to be the site of follicular stem cells. The hair bulb at the tip of the papilla contains progeny of the parafollicular bulge stem cells. These progeny in turn are a proliferative population which gives rise to the hair. We asked the question: Does GVHD preferentially attack the younger, less differentiated population of cells in the parafollicular bulge but spare the also cycling, later generation of cells in the papillary bulb? We had 22 evaluable cases from our prior study of 38 biopsies of GVHD patients: 19 showed preferential bulge involvement, 2 showed both involved, 1 showed neither involved and none showed bulb positive and bulge negative. The data support a strong preference for GVHD to attack the less differentiated of two cell populations both of which are cycling, thereby supporting the hypothesis that preferred targets are related to the stem cell populations in epithelial and not just all cycling or proliferating populations.