Significance of anti-desmocollin autoantibodies in pemphigus.

Abstract

The major autoantigens for pemphigus are desmogleins (Dsgs), cell-cell adhesive structure proteins, one of the desmosomal cadherins. Recent progress in molecular biology has revealed that IgG autoantibodies of classical pemphigus react with Dsg1 or Dsg3. Desmocollins (Dscs) also belong to the cadherin supergene family that provides structure to the desmosomes and play an important role in cell-to-cell adhesion. In addition to the presence of four desmosomal Dsg isoforms, i.e. Dsg1-4, Dsc1, 2 and 3, all of which are derived from different genes, Dsc1 has been previously identified as the target antigen of IgA autoantibodies in the subcorneal pustular dermatosis (SPD)-type of intercellular IgA dermatosis. In addition to the IgA anti-Dsc1 autoantiboides, the presence of IgG anti-Dsc autoantibodies is described in patients of some autoimmune bullous diseases. In particular, the current pemphigus detecting autoantibodies to Dscs has shown a tendency in atypical variants of pemphigus. Therefore, autoantibodies against Dscs alone may cause detachment of cell-cell adhesion in the epidermis in some pemphigus. However, except for the findings of a few in vitro and in vivo studies, there is currently no clear evidence for the pathogenicity of anti-Dsc autoantibodies in pemphigus, whereas significance of anti-Dsg autoantibodies is well established. This article describes the structure and function of the Dscs, and explores the evidence regarding the pathogenic role of anti-Dsc autoantibodies in pemphigus.