# Localization of Lesions in Autoimmune Blistering Diseases Is Independent of Site-Specific Target Antigen Expression

## TL;DR

This study finds that the location of skin lesions in autoimmune blistering diseases is not determined by where target antigens are expressed in the body.

## Contribution

The study shows that lesion localization in AIBDs is independent of antigen expression, challenging previous assumptions.

## Key findings

- BP lesions commonly occur on arms and legs, while PV and PF lesions affect mucosa and the back.
- Regional differences in antigen expression do not correlate with lesion frequency or severity.
- Factors like microbiota, mechanical stress, and local immunity may influence lesion localization.

## Abstract

Autoimmune blistering diseases (AIBDs) involve autoantibodies targeting proteins in the epidermal/epithelial desmosome (pemphigus) or basement membrane zone (pemphigoid). Despite widespread antigen distribution, lesions exhibit a scattered involvement pattern. This study maps the frequency/severity of AIBD lesions on various body parts and investigates whether differential antigen expression contributes to specific predilection sites. We analyzed affected sites presenting blisters/erosions, erythematous/urticarial lesions, and mucosal lesions in bullous pemphigoid (BP-cohort 1, n = 65; BP-cohort 2, n = 119), pemphigus vulgaris (PV, n = 67), and pemphigus foliaceus (PF, n = 20) patients. To assess antigen expression, we conducted indirect immunofluorescence (IF) staining of 11 AIBD antigens from 13 anatomical sites of 10 body donors without AIBD. In BP, blisters/erosions and erythematous/urticarial lesions predominantly affected arms and legs, while PV/PF patients exhibited frequent involvement of buccal mucosa and back, respectively. IF staining identified significant regional differences in BP180, BP230, and integrin β4 expression, although these variations did not correlate with a higher lesion frequency/severity. Other antigens showed consistent expression across all regions. Our findings suggest that predilection sites for BP and PV/PF are largely unaffected by regional variations in antigen expression but may be influenced by factors like microbiota, mechanical stress, sunlight exposure, local immunity, or genetics.