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.

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.

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