Pemphigus vulgaris is caused by an autoimmune reaction in which the body’s immune system mistakenly attacks a specific protein called desmoglein 3, which is essential for holding skin cells together. This attack leads to the production of autoantibodies—immune proteins that target the body’s own tissues—specifically against desmoglein 3. Desmoglein 3 is a critical adhesion molecule located in the skin and mucous membranes, responsible for maintaining the integrity and cohesion of skin cells. When these autoantibodies bind to desmoglein 3, they disrupt the connections between skin cells, causing them to separate and leading to painful blisters and erosions characteristic of pemphigus vulgaris.
The root cause of this autoimmune response involves B cells, a type of immune cell that normally produces antibodies to fight infections. In pemphigus vulgaris, certain B cells become misdirected and produce antibodies against desmoglein 3 instead of harmful invaders. This abnormal immune activity is what drives the disease process. The exact trigger for why the immune system starts targeting desmoglein 3 is not fully understood, but it likely involves a combination of genetic predisposition and environmental factors that confuse the immune system into recognizing this self-protein as foreign.
On a molecular level, the binding of autoantibodies to desmoglein 3 not only physically disrupts cell adhesion but also activates signaling pathways inside the skin cells. These signals can alter calcium levels within the cells and activate enzymes that weaken the connections between cells, further promoting blister formation. This dynamic signaling cascade amplifies the damage caused by the autoantibodies and contributes to the severity of the disease.
In summary, pemphigus vulgaris arises because the immune system produces autoantibodies targeting desmoglein 3, a key molecule that keeps skin cells stuck together. This autoimmune attack breaks down the skin’s structural integrity, leading to blistering and sores. The disease is mediated by specific B cells that mistakenly recognize desmoglein 3 as a threat, and the resulting immune response triggers cellular changes that worsen the skin damage. Understanding this mechanism has led to the development of targeted therapies that aim to selectively remove or inhibit these harmful B cells, offering hope for more effective and safer treatments.
