Desmoglein antibody titers and loss of keratinocyte adhesion in vitro are associated with disease severity in patients with Pemphigus Vulgaris Público

Abstract

Pemphigus vulgaris (PV) is an autoimmune bullous disease characterized by severe epidermal blistering and mucous membrane erosions. PV is caused by antibodies directed against the desmosomal cadherin desmoglein 3 (Dsg3), and in cases involving the skin, both Dsg3 and Dsg1. PV can be assessed clinically using the Pemphigus Disease Area Index (PDAI) and by ELISA for anti-Dsg IgG titers in patient sera. In vitro, PV IgG activity can be investigated by incubating normal human keratinocytes with PV patient IgG and monitoring changes in strength of cell-cell adhesion caused by desmosome disruption using a dispase-based cell-cell dissociation assay. However, the relationship between clinical PV assessments and in vitro activity of patient IgG have not been systematically evaluated. In the present study, we compared the relationship between the in vitro pathogenicity of PV IgG from 23 patients to their PDAI score and ELISA titers. Overall, Dsg1 ELISA values showed a stronger correlation with PDAI scores (r=0.56, p<0.001) when compared to Dsg3 ELISA (r=0.45, p<0.02). However, the sum of Dsg3 and Dsg1 ELISA values exhibited the strongest correlation to PDAI (r=0.67, p<0.0001). Additionally, the loss of cell-cell adhesion strength as assessed using in vitro dispase cell dissociation assays exhibited a positive correlation with Dsg3 ELISA titers (r=0.54, p<0.005), supporting the validity of the dispase assay as a measure of PV pathogenicity. These findings confirm the association of Dsg ELISA values with PDAI and establish a relationship between Dsg IgG titers in patients and loss of adhesion in cultured keratinocytes. 

Table of Contents

Introduction…1

Background…2

Material and Methods…5

Results…9

Discussion and Conclusions…11

References…15

Tables and Figures…17

About this Master's Thesis

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School	Laney Graduate School
Department	Clinical Research
Degree	M.S.
Submission	Master's Thesis
Language	English
Research Field	Health Sciences, Medicine and Surgery Biology, Cell
Palabra Clave	pemphigus
Committee Chair / Thesis Advisor	Amita Manatunga, Emory University
Committee Members	Howa Yeung, Emory University Andrew Kowalczyk, Emory University

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