A 72-year-old man with a 2-month history of recurrent bullous eruptions on the abdomen and inner thighs is referred to dermatology. Histopathology shows subepidermal blister formation with eosinophil-rich infiltrate. Indirect immunofluorescence (IIF) on patient's serum is positive. Which of the following antibodies is most likely responsible for this patient's disease?

## Autoantigen Identification in Bullous Pemphigoid **Key Point:** Bullous pemphigoid is mediated by **IgG autoantibodies against BP180 (collagen XVII) and BP230**, which are components of hemidesmosomes at the basement membrane zone. ## Hemidesmosomal Structure and Antigens **High-Yield:** Hemidesmosomes anchor the basal keratinocytes to the basement membrane. The two major autoantigens in BP are: 1. **BP180 (collagen XVII)** — transmembrane protein, most common target 2. **BP230** — cytoplasmic protein, less frequently involved **Clinical Pearl:** **Indirect immunofluorescence (IIF) positivity** in bullous pemphigoid indicates circulating IgG antibodies against these basement membrane antigens. This is highly specific for BP and can be used for serological diagnosis and monitoring disease activity. ## Serological Markers in Bullous Disorders | Disorder | Primary Antibody | IIF Result | DIF Pattern | |----------|------------------|------------|-------------| | Bullous pemphigoid | Anti-BP180, Anti-BP230 | Positive (IgG) | Linear IgG + C3 at BMZ | | Pemphigus vulgaris | Anti-Dsg3 ± Anti-Dsg1 | Positive (IgG) | Intercellular IgG | | Dermatitis herpetiformis | Anti-tTG | Negative | Granular IgA at DEJ | | Linear IgA disease | Anti-BP180 (subset) | Variable | Linear IgA at BMZ | ## Pathogenic Mechanism ```mermaid flowchart TD A[Autoimmune response against BP180/BP230]:::outcome --> B[IgG antibody production] B --> C[Circulating IgG detected on IIF] C --> D[Antibodies bind to basement membrane zone] D --> E[Complement activation and eosinophil recruitment] E --> F[Subepidermal blister with eosinophilic infiltrate] F --> G[Clinical bullae]:::outcome ``` ## Why IIF is Positive in This Patient **Mnemonic:** **BP-IIF** = **B**asement membrane **P**rotein antibodies detected by **I**ndirect **I**mmunofluorescence. 1. Patient's serum contains anti-BP180 and/or anti-BP230 IgG 2. When serum is incubated on normal human skin, these antibodies bind to the basement membrane zone 3. Fluorescein-conjugated anti-human IgG reveals linear staining at the dermal-epidermal junction 4. This confirms the diagnosis and reflects active disease **Key Point:** IIF positivity correlates with disease activity and can be used to monitor response to treatment.