The immunology of alopecia areata and potential application to novel therapies

Abstract

There is strong evidence indicating alopecia areata (AA) is a tissue-specific, autoimmune disease. Hair loss is associated with a perifollicular lymphocytic infiltrate made up primarily of CD4+ cells, associated with a CD8+ intrafollicular infiltrate. Evidence of immune activation includes expression of human leukocyte antigen (HLA)-DR, HLA-A,B,C, and intercellular adhesion molecule (ICAM)-1 on the follicular epithelium. It is likely that the follicular expression of HLA-DR and ICAM-1 is induced by interferon (IFN)-γ produced by T cells. Antibodies to follicular epithelium are often present, but their significance is not known. Lesional scalp from AA patients grafted onto nude mice regrows hair coincident with a loss of infiltrating lymphocytes from the graft. It is possible to transfer hair loss to human scalp explants on severe combined immunodeficiency (SCID) mice by injection of lesional T cells. Neuropeptides produced by cutaneous nerves may modify immune reactivity and influence disease. In particular, low levels of the calcitonin gene-related peptide (CGRP) may have a role in initiation of the condition by inducing immune hyperresponsiveness and vasoconstriction. Best evidence is that AA is a mediated by a TH1 T-lymphocyte response. Translation of these data into potential new therapies is discussed.