# Structure and mechanism of pemphigus autoantibodies

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2021 · $477,355

## Abstract

Pemphigus is a group of potentially life-threatening antibody-mediated autoimmune diseases of
the skin and other stratified epithelia in which acantholysis – the loss of cell adhesion – causes
skin blistering and erosions. Acantholysis in pemphigus is caused by autoantibodies directed
against desmosome cell-adhesive junctions – specifically against the transmembrane cadherin-
family proteins that bind between cells to mediate adhesion in desmosomes. Several subtypes
of pemphigus disease are known, including two major forms pemphigus vulgaris (PV) and
pemphigus foliaceus (PF). Broadly, PV is characterized by acantholysis in the basal layers of
mucosae (mucosal form) or mucosae and skin (muco-cutaneous form), while PF is
characterized by acantholysis specifically in the subcorneal upper layers of the skin.
Pathogenic pemphigus autoantibodies have been identified from patients with each form of the
disease, but structural information on pemphigus autoantibodies is lacking. Thus, the precise
epitopes targeted by pemphigus autoantibodies, and the antibody regions (paratopes) that
mediate recognition, remain unknown. The overall goal of the research proposed here is to
bring atomic-level definition to the study of pemphigus disease through the application of
modern methods of structural biology. Atomic resolution co-crystal structures will
unambiguously identify functional regions and define the precise molecular interactions
mediating recognition between pemphigus autoantibodies and the cadherin cell-adhesion
proteins they target. In addition, to determine how different pemphigus autoantibodies impair
desmosome structure and cause blistering, we will analyze their effects on reconstituted
desmosome junctions at high resolution using cryo-EM tomography. The research proposed
here will produce an atomic-level understanding of the interaction of pemphigus autoantibodies
with desmosomes, and is expected to transform our understanding of pemphigus disease.

## Key facts

- **NIH application ID:** 10168462
- **Project number:** 5R01AR073846-04
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** LAWRENCE S SHAPIRO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $477,355
- **Award type:** 5
- **Project period:** 2018-08-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10168462

## Citation

> US National Institutes of Health, RePORTER application 10168462, Structure and mechanism of pemphigus autoantibodies (5R01AR073846-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10168462. Licensed CC0.

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