A 72-year-old woman with a 6-month history of recurrent tense bullae and urticarial plaques is referred for immunological workup. Serology shows circulating IgG antibodies against the basement membrane zone. Which is the most common antigen target in bullous pemphigoid?

Explanation

## Antigen Targets in Bullous Pemphigoid **Key Point:** **BP180 (collagen XVII)** is the most common and clinically significant antigen target in bullous pemphigoid, present in >90% of BP sera. ### Comparison of BP Antigens | Antigen | Structure | Frequency in BP | Clinical Significance | Serology | |---------|-----------|-----------------|----------------------|----------| | **BP180 (collagen XVII)** | Transmembrane hemidesmosomal protein | >90% | Most common; correlates with disease activity | IgG (linear IgG/IgA) | | **BP230 (BPAG1)** | Cytoplasmic hemidesmosomal protein | 60–70% | Often co-present with BP180 | IgG | | Desmoglein 3 (Dsg3) | Desmosomal cadherin | NOT in BP | Pemphigus vulgaris antigen | IgG | | Envoplakin | Plakin family protein | Rare in BP | Associated with paraneoplastic pemphigus | IgG | ### BP180 Structure and Function 1. **Transmembrane protein** — anchors the hemidesmosome to the basement membrane 2. **Ectodomain** — extracellular domain; primary target of autoimmune attack 3. **NC16A domain** — immunodominant region; most frequently recognized by patient antibodies 4. **Pathogenic role** — anti-BP180 IgG directly disrupts hemidesmosomal adhesion **High-Yield:** Anti-BP180 seropositivity is present in ~90% of bullous pemphigoid patients and correlates with disease activity and severity. Anti-BP230 alone (without anti-BP180) is rare and may indicate a milder or localized form. **Clinical Pearl:** Serum anti-BP180 IgG levels often correlate with disease activity — a rising titer may predict relapse, making it useful for monitoring treatment response. **Mnemonic: "BP180 = Transmembrane; BP230 = Cytoplasmic; 180 is the main one"** — remember that BP180 is the primary and most frequent target. ### Why BP180 and Not BP230? - **BP180 is the dominant antigen** — recognized by >90% of BP sera - **BP230 is secondary** — present in ~60–70% and usually co-exists with BP180 - **Serology-pathology correlation** — anti-BP180 shows the strongest correlation with active disease [cite:Harrison 21e Ch 297]