A 48-year-old man with a 6-week history of recurrent oral erosions and flaccid blisters on the trunk is suspected to have pemphigus vulgaris. Which is the most common autoantigen targeted in pemphigus vulgaris?

Explanation

## Most Common Autoantigen in Pemphigus Vulgaris **Key Point:** Desmoglein 3 (Dsg3) is the most common and often the sole autoantigen in pemphigus vulgaris, particularly in mucosal-dominant disease. ### Autoantigen Classification in Pemphigus | Pemphigus Type | Primary Autoantigen | Secondary Antigen | Clinical Pattern | |---|---|---|---| | **Pemphigus Vulgaris (Mucosal-dominant)** | **Dsg3** | — | Oral + limited cutaneous | | **Pemphigus Vulgaris (Mucocutaneous)** | **Dsg3 + Dsg1** | — | Oral + extensive cutaneous | | **Pemphigus Foliaceus** | Dsg1 | — | Superficial, cutaneous only | | **Paraneoplastic pemphigus** | Dsg3, Dsg1, envoplakin, periplakin | Multiple | Severe, often fatal | **High-Yield:** Anti-Dsg3 antibodies alone → **mucosal-dominant pemphigus vulgaris** (oral erosions, limited skin involvement). Anti-Dsg3 + Anti-Dsg1 antibodies → **mucocutaneous pemphigus vulgaris** (extensive oral and cutaneous disease). ### Pathophysiology of Dsg3-Mediated Acantholysis 1. **IgG autoantibodies** bind to Dsg3 (a transmembrane glycoprotein in desmosomes). 2. **Disruption of cell-to-cell adhesion** → Loss of desmosomal integrity. 3. **Suprabasal acantholysis** → Separation of basal cells from suprabasal layers. 4. **Blister formation** → Intraepidermal blisters with characteristic "tombstone" appearance on histology. **Clinical Pearl:** The **antibody profile predicts clinical phenotype**: - Anti-Dsg3 alone = mucosal-dominant (better prognosis) - Anti-Dsg3 + Anti-Dsg1 = mucocutaneous (more severe) ### Diagnostic Confirmation **Mnemonic:** **DIF-IIF-ELISA** (Direct/Indirect Immunofluorescence and ELISA for antibody detection) 1. **Direct Immunofluorescence (DIF)** — Intercellular IgG and C3 in perilesional skin ("tombstone" pattern). 2. **Indirect Immunofluorescence (IIF)** — Circulating IgG antibodies against intercellular substance. 3. **ELISA** — Quantifies anti-Dsg3 and anti-Dsg1 antibody levels (correlates with disease severity). **Tip:** In a patient with oral erosions and flaccid blisters, if DIF shows intercellular IgG and anti-Dsg3 is positive, the diagnosis is pemphigus vulgaris until proven otherwise. [cite:Harrison 21e Ch 297]