HLA and ICAM-1 expression in alopecia areata in vivo and in vitro: The role of cytokines

Abstract

To investigate the hypothesis that aberrant HLA and adhesion molecule expression in alopecia areata (AA) are secondary to local release of interferon-gamma (IPN-γ) or other cytokines, we have studied HLA ABC, -DQ, -DR and ICAM-1 expression by immunohistochemistry, and compared patterns of expression in lesional tissue sections with those observed in hair follicles maintained in short-term organ culture, both from normal individuals and non-lesional sites in AA patients. The organ cultures were supplemented with IFN-γ, tumour necrosis factor-alpha (TNF-α), and granulocyte-macrophage colony stimulating factor (GM-CSF), in a range of doses. In lesional AA tissue sections, there was close spatial correlation of ICAM-1 with HLA-DR; prominent staining being noted in the pre-cortical matrix and dermal papilla (DP) of lesional anagen follicles. In cultured follicles, dose-dependent induction of HLA class I, DR and ICAM-1 by IFN-γ, and HLA class I and ICAM-1, but not HLA-DR, by TNF-α was observed in follicular epithelium, mainly in the outer root sheath (ORS). The findings in these cultures were the same in follicles derived from normal individuals and AA patients. Cytokine-induced patterns of HLA and ICAM-1 expression observed in vitro in cultured follicles differed significantly from those observed in vivo in lesional tissue sections. In particular, IFN-γ failed to induce HLA-DR expression in the pre-cortical matrix and dermal papilla (DP), sites where this is usually observed in AA. The results suggest local cytokine release is not the sole determinant of aberrant HLA-DR expression in AA.