Conclusion and Prospects
Sufficient is now understood about the pathogenesis of vitiligo to
permit targeted pharmacological intervention at the appropriate
immunological steps. However, the exact modus by which the genetic
interacts with the environment, and with the immune system still
requires considerable elucidation. What can be said is that both
environmental factors and cell-intrinsic defects instigate stress
responses in melanocytes, resulting in the synthesis of DAMPs that
elicit innate immune cells, which in turn activate adaptive immunity
that ultimately targets melanocytes. A genetic predisposition to
autoimmunity may underlie inappropriate immune responses in vitiligo,
but immune responses may occur secondarily as a result of melanocyte
damage by other factors, as when autoantibodies have been observed
directed against intracellular pigment cell proteins — exposure of
cryptic epitopes and protein modification occurring during apoptosis
[215]. Following processing by dendritic cells, antigenic proteins
can be presented to either autoreactive T cells, which evaded clonal
deletion, or to naïve T cells, which have not been tolerised against
cryptic epitopes [216]. In consequence, antibodies can be secreted
following autoreactive B cell stimulation by activated autoreactive CD4+
T lymphocytes [216], which may then act to further aggravate
vitiligo. However, it is possible that antibodies play no part in the
pathogenesis of vitiligo, but might indicate the existence of
autoreactive anti-melanocyte T cells are capable of destroying
melanocytes, a scenario that merits further investigation.