Convergence Theory
The convergence theory attempts to link together the potential causal
mechanisms of vitiligo [210]. It suggests multiple sequential stages
in pathogenesis beginning with an elicitation stage perhaps due to
mechanical friction and skin trauma, emotional stresses, chemical
exposure or imbalances in endogenous neural factors, metabolites,
cytokines or hormones [5, 206, 211-214]. Such factors, in an
individual whose genetic make-up predisposes to immune activation and
melanocyte destruction, it is proposed result in oxidative stress within
melanocytes which subsequently express HSP70 and chaperoned melanocyte
antigens, presented by dendritic cells to T cells in regional lymph
nodes, resulting in proliferation of melanocyte-specific cytotoxic T
cells and melanocyte destruction — the stage of immune activation
[54, 135, 166].
Absent or reduced fully-functional skin-infiltrating Tregs contribute to
the on-going immune response and disease spread [86]. Antibodies
against melanocyte-specific proteins such as tyrosinase, generated in
response to melanocyte destruction, damage pigment cells by activating
complement or by antibody-dependent cellular cytotoxicity [122,
133].