Correlation of Clinical and Histopathological Features With Anti‐Desmoglein Antibody Profile in Pemphigus Patients

Background

The desmoglein compensation hypothesis (DCH) proposes that clinical and histopathological features of pemphigus correlate with differential expression of desmoglein 1 (Dsg1) and desmoglein 3 (Dsg3) in skin and mucosa, and corresponding autoantibody profiles. While DCH explains many classical patterns, increasing exceptions have challenged its universality.

Aim

This study aimed to correlate clinical phenotype and histopathological split level with anti‐Dsg1 and anti‐Dsg3 antibody profiles in pemphigus vulgaris (PV) and pemphigus foliaceus (PF), and evaluate consistency with DCH.

Methods

In this bicentric retrospective study, 106 patients with confirmed pemphigus (93 PV, 13 PF) were included. Clinical classification was based on presentation (cutaneous, mucosal, mucocutaneous). Histopathology was reviewed for split level (subcorneal, suprabasal, dual), and serum Dsg1/Dsg3 IgG levels were recorded. Concordance with DCH was assessed.

Results

In PF, splits were subcorneal in 6 (46.2%), suprabasal in 3 (23.1%), and both in 4 (30.7%). Eight (61.5%) had isolated anti‐Dsg1 IgG, consistent with DCH. In PV, 75 (80.6%) had suprabasal splits, 7 (7.5%) dual splits, and 4 (4.3%) subcorneal splits. Among 16 mucosal PV cases, only 6 (37.5%) had isolated anti‐Dsg3 IgG. Highest fidelity to DCH was seen in mucocutaneous PV (56/75; 74.7%) with dual anti‐Dsg1 and Dsg3 positivity. Two patients with cutaneous‐only PV showed dual positivity with suprabasal splits.

Conclusion

While DCH explains many classic presentations, nearly one‐third of patients in our cohort exhibited discordant clinical, serologic, or histologic features. These findings highlight the need for more comprehensive models of pemphigus pathogenesis that incorporate antibody titers, affinity, subclass, and non‐desmoglein targets.

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