Pemphigus Vulgaris: A Closer Look
Pemphigus vulgaris is a serious but rare autoimmune disorder of the epithelial cells and mucosal lining of the skin. The first cases were recorded by McBride in 1771 and by Whichman in 1979. McBride was to describe the first to casualties as being caused by “bloody ichor” and “putrid ulcers”. (Jordon, 2013) However, Whichman was the one who would originally name the disease as pemphigus. The word “pemphigus” is of Greek origin which means blister or bubble. (Jordon, 2013) As the name suggests, this disease causes painful blisters or bullous erosions of the squamous epithelia and mucous membranes. It can be sub-classified based on the location of the lesions in the epidermis. Pemphigus vulgaris is considered to be one of the deep forms of the disease. The lesions appear deep into the epidermis of the skin right above the basal lamina. (Zeina, 2013)
The autoimmune process that causes pathogenicity is the formation and activation of antibodies targeting the keratinocyte desmosomal cadherins or for simplicity desmosomes. The latter is responsible for the adherence of keratinocytes, and when it is targeted by these antibodies the desmosomes lose their ability to maintain keratinocytes together and the cells become detached. “Ultrastructural studies of pemphigus lesions have suggested that dissolution of desmosomes may result in the formation of blisters. This is a phenomenon known as acantholysis.” (Loannides, Lazaridou, Rigopolous, 2008)
Studies have shown that the antigens responsible for this autoimmune attack have components of the actual desmosome. Two transmembrane glycoproteins have been identified. One being desmoglein ( Dsg) and desmocollin (Dsc). Both of these have three isoforms (1-3) and belong to the cadherins. Dsg-I is the primary isoform expressed in the saquamous epithelium, while Dsc-3 is the isoform that is expressed on the mucosa. Nevertheless, new studies and microscopy analysis have shown that autoantibodies not only bind to the Dsg ‘s desmosomal protein but to the Dsc’s desmosomal proteins as wells or along structures of the keranocytes. (Loannides, Lazaridou, Rigopolous, 2008)
The autoantibodies produced by this disease are polyclonal and the majority of them found circulating are of the immunoglobulin subclass 4 (IgG4). This antibody is found patients who have the active disease, while those who are on remission mainly have the IgG1. This antibody targets DSG-3, however it is considered to be non-pathogenic. Therefore, it has been extrapolated that clinical pathology is caused by some trigger that causes the presence of HLA susceptibility genes which in turn is necessary for the production of IgG4. (Loannides, Lazaridou, Rigopolous, 2008) HLA serotypes DR4 and DR6 are particularly strongly associated. In someone with the active disease, the Major Histocompatibility Complex II (MHC II) activates the Th2 cells. These cells then in response activate the B-cells which then begin...