Low pH condition impairs BP-IgG binding to the basement membrane zone.

Area of Science:

• Immunodermatology
• Autoimmune Blistering Diseases
• Diagnostic Immunology

Background:

• Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disease.
• Direct immunofluorescence (DIF) detects tissue-bound Immunoglobulin G (IgG) at the basement membrane zone (BMZ), a key diagnostic marker for BP.
• Complement component 3 (C3) shows higher sensitivity than IgG in DIF for BP diagnosis, but the underlying mechanism is unclear.

Purpose of the Study:

• To investigate the mechanism behind IgG negativity and C3 positivity at the BMZ in some BP cases using DIF.
• To explore the influence of pH on autoantibody binding and deposition at the BMZ in BP.

Main Methods:

• Ex vivo studies using sera from BP patients with IgG-negative DIF results.
• Indirect immunofluorescence (IIF) with sera diluted in phosphate-buffered saline (PBS) at varying pH levels (7.4, 6.0, 3.0).
• Pre-incubation of BP skin sections with different pH PBS before staining for IgG and C3.

Main Results:

• BP patient sera reacted to the BMZ, but fluorescence intensity decreased at lower pH (6.0 and 3.0).
• Pre-incubation of skin sections with low pH PBS (3.0 and 6.0) significantly reduced IgG and C3 fluorescence intensity compared to neutral pH (7.4).
• Results suggest low pH hinders autoantibody binding and promotes detachment from the BMZ.

Conclusions:

• Inflammation-induced low tissue pH inhibits autoantibody deposition and causes detachment from the BMZ.
• While IgG may detach under acidic conditions, complement fragments can remain, explaining higher C3 sensitivity in DIF for BP diagnosis.
• Understanding the role of pH in autoantibody binding offers insights into BP pathogenesis and diagnostic sensitivity.