HDIG does not directly inhibit activities of pathogenic IgG. Pathogenic IgG (1 mg/ml R530, anti-Dsg1 from PF1, or anti-Dsg3 from PV1) was incubated with buffer control, IgM, or HDIG (25 mg/ml) at room temperature for 1 hour. (A) Supernatants containing anti-mBP180 IgG coincubated with buffer or HDIG showed the same IF staining density at the basement membrane zone. Supernatants containing anti-Dsg1 (B) or anti-Dsg3 (C) IgG coincubated with buffer or HDIG showed the same IF staining density at the keratinocyte cell surface. Supernatants with IgM preabsorption showed the same IF density (data not shown). (D) Supernatants containing anti-mBP180 (equivalent to 25 μg/g body weight), anti-Dsg1 (equivalent to 40 μg/g body weight), or anti-Dsg3 (equivalent to 50 μg/g body weight) preabsorbed with buffer (bars 1, 3, and 7), IgM (bars 2, 5, and 8), or HDIG (bars 3, 6, and 9), when injected intradermally into WT or FcRn–/– mice (Table 2), induced BP (bars 1–3), PF (bars 4–6), and PV (bars 7–9) clinical blisters, respectively, 48 hours after pathogenic IgG administration. (E). ELISA revealed similar levels of serum pathogenic anti-mBP180 (bars 1 and 2), anti-Dsg1 (bars 4 and 5), and anti-Dsg3 (bars 7 and 8) in mice injected with supernatants preabsorbed with buffer (bars 1, 4, and 7) and IgM (bars 2, 5, and 8). As expected, serum levels of pathogenic IgG were reduced in mice injected with supernatants preabsorbed with HDIG (bars 3, 6, and 9). n = 6. *P < 0.01.