Further evidence for the central role of T-lymphocyte cells in the pathology of AA comes from animal studies in which bald, lesional scalp sections, removed at biopsy from AA patients, will re-grow hair when grafted onto nude mice, a specialized laboratory species that does not produce T-cells. The reverse is also true in that hair loss can be induced from normal human scalp explants that are grafted onto a similar strain, the severe-combined lymphocyte immunodeficient (SCID) mouse, if T-lymphocytes obtained from AA scalp lesions are then injected into the host animals. In laboratory experiments, T-lymphocytes from AA patients can be activated in vitro if they are exposed to follicle and even melanocyte (pigment producing skin cells) cell preparations. Analysis of scalp biopsies reveals the presence of markers of inflammation within the epithelial cells that line the follicles of AA patients, such as the antigen presentation histocompatability molecules HLA-DR; HLA-A,B,C; and the adhesion molecule ICAM-1. These markers of inflammation are induced by interferon-gamma, an inflammatory chemical (a cytokine) released by activated T-lymphocytes.
Hair follicles are the target
A big clue as to what these T-cells might be reacting to comes from the fact that AA primarily affects the hair follicle as it enters the prolonged growth phase called anagen. During this stage in the hair cycle, proteins such as hair-specific keratin and trichohyalin are produced in the inner root sheath of the growing hair follicle. These are amongst the candidate targets for the immune system in AA currently being studied. Evidence that antibody-generating B-lymphocyte cell autoimmune responses to hair follicles appear to act in concert with the T-cells during the course of an AA attack responses comes from data generated from numerous studies demonstrating the presence of numerous anti-hair follicle antibodies in the sera of AA patients.
Treatment of AA and the potential benefit of recent scientific developments
Current treatment strategies are aimed at limiting the inflammation that the autoimmune reaction causes. As such, the most common first-line therapies are local injection of corticosteroids (cortisone) if the disease is patchy, or oral corticosteroids (cortizone tablets) if the disease is more widespread. 5% Minoxidil ointment is also employed as a therapeutic intervention. Diphencyprone (DPCP) or Squaric Acid Dibutyl Ester (SADBE) treatments are other options. These are designed to counteract the underlying immunogenic autoimmune reaction with a localized allergic reaction, inducing hair growth as a result. On the whole, current therapies are not very sophisticated or specific and are associated with significant side effects. A better understanding of the autoimmune response that drives AA is the first step in the development of novel, more targeted therapies. These include and mechlorethamine, anti-interferon-gamma and other anti-immune modulating protein antibodies that block the follicle-targeted inflammatory response. These have already been proven as efficacious in reversing hair loss in mouse models of AA and in limited human trials studies. This is very good news for the many individuals currently afflicted with this most aggressive form of hair loss and guarantees that more sophisticated, effective and safer treatments are not too far around the corner, hopefully becoming available to patients within next few years.
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