Pemphigus vulgaris is characterized by acantholysis. Which of the following cell adhesion molecules is primarily targeted by autoantibodies in this condition?

Explanation

## Autoantigen in Pemphigus Vulgaris **Key Point:** Pemphigus vulgaris is an autoimmune blistering disorder in which IgG autoantibodies target desmogleins, which are transmembrane glycoproteins of the desmosome. ### Desmoglein Subtypes and Clinical Correlation | Antibody Target | Clinical Presentation | Histology | |---|---|---| | **Desmoglein 3 only** | Mucosal-dominant PV (oral erosions, limited skin involvement) | Suprabasal acantholysis | | **Desmoglein 3 + Desmoglein 1** | Mucocutaneous PV (oral + extensive skin blisters) | Suprabasal + superficial acantholysis | | **Desmoglein 1 only** | Pemphigus foliaceus (superficial, no mucosal involvement) | Subcorneal/granular layer acantholysis | **High-Yield:** The **desmoglein compensation theory** explains why anti-Dsg3 antibodies alone cause mucosal disease: Dsg1 can partially compensate in skin but NOT in mucosa (which lacks Dsg1). **Clinical Pearl:** Serum anti-Dsg3 and anti-Dsg1 antibody titers correlate with disease activity and can be used to monitor treatment response. ### Why Other Molecules Are Not Targeted - **Desmoplakin and plectin:** These are intracellular plakin proteins; they are structural components but not primary autoantigens in PV. - **Integrin α6β4:** This is the hemidesmosmal adhesion molecule; it is targeted in bullous pemphigoid, not pemphigus vulgaris. - **E-cadherin and N-cadherin:** These are classical cadherins found in adherens junctions; they are not the primary target in PV (though cross-reactivity may occur in some cases). **Mnemonic:** **DES**mogleins in **PEM**phigus — **Desmoglein 3** is the core antigen; add **Desmoglein 1** for mucocutaneous disease.