Human Desmocollin 1 (Dsc1) Is an Autoantigen for the Subcorneal Pustular Dermatosis Type of IgA Pemphigus

Abstract

IgA pemphigus showing IgA anti-keratinocyte cell surface autoantibodies is divided into subcorneal pustular dermatosis (SPD) and intraepidermal neutrophilic IgA dermatosis (IEN) types. We previously showed by immunoblotting that IgA from some IgA pemphigus patients reacted with bovine desmocollins (Dsc), but not human Dsc. To determine the antigen for IgA pemphigus, we focused on conformation-dependent epitopes of Dsc, because sera of patients with classical pemphigus recognize conformation-sensitive epitopes of desmogleins. We constructed mammalian expression vectors containing the entire coding sequences of human Dsc1, Dsc2, and Dsc3 and transiently transfected them into COS7 cells by lipofection. Immunofluorescence of COS7 cells transfected with single human Dscs showed that IgA antibodies of all six SPD-type IgA pemphigus cases reacted with the surface of cells expressing Dsc1, but not with cells expressing Dsc2 or Dsc3. In contrast, none of seven IEN-type IgA pemphigus cases reacted with cells transfected with any Dscs. These results convincingly indicate that human Dsc1 is an autoantigen for SPD-type IgA pemphigus, suggesting the possibility of an important role for Dsc1 in the pathogenesis of this disease. This study shows that a Dsc can be an autoimmune target in human skin disease.

Autoimmunity to Desmocollin 3 in Pemphigus Vulgaris

“…Previous studies have not identified significant Dsc3 autoreactivity in the sera of PV patients. However, many of these studies used ELISA, which has been shown to be suboptimal for detecting autoreactive antibodies to desmocollin 1 in cases of IgA pemphigus, 32 potentially due to destruction or masking of epitopes. We have similarly found that autoreactive Dsc3 epitopes are not significantly detected by ELISA testing of pemphigus sera, in part due to the sensitivity of these epitopes to freezing and thawing (data not shown).…”

Spectrum of dominant mutations in the desmosomal cadherin desmoglein 1, causing the skin disease striate palmoplantar keratoderma

“…10 European Journal of Human Genetics Desmosomal cadherin mutations DM Hunt et al 201 structure and function in the epidermis. Similarly although some cases of pemphigus have now been attributed to desmocollin autoantigens, 45 nevertheless most pemphigus cases are due to autoimmunity involving Dsg1 and Dsg3. The desmogleins differ from the desmocollins in containing a region at their C-terminus made up of a number of unique repeats which is predicted to form an anti-parallel b-sheet and which can be visualised as a knob-like structure.…”

Imunofluorescência direta e indireta

“…[19][20] Subepidermal bullous dermatosis Bullous pemphigoid IIF: It shows circulating antibodies of the anticollagen XVII (BP180) IgG class in 70% of the patients. It appears that there is no correlation between antibody titers and the extension or activity of the disease.…”