The involvement of ADAM10 in acantholysis in mucocutaneous pemphigus vulgaris depends on the autoantibody profile of each patient
Keywords: 
Materias Investigacion::Ciencias de la Salud::Dermatología
Materias Investigacion::Ciencias de la Salud
Pemphigus vulgaris
Non‐Dsg autoantibodies
PV‐IgG fractions
ADAM10‐dependent
Issue Date: 
2020
Publisher: 
Oxford
Project: 
info:eu-repo/grantAgreement/MINECO/Proyectos de investigación en salud (Modalidad Proyectos de investigación en salud) (AE Salud 2016)/PI16/00129/[ES]/TRATAMIENTO DEL INFARTO DE MIOCARDIO Y PREVENCIÓN DEL REMODELADO ADVERSO MEDIANTE LA APLICACIÓN DE FACTORES DE CRECIMIENTO Y MICRORNAS ANTI-FIBRÓTICOS
ISSN: 
1365-2133
Citation: 
Ivars-Lleó, M. (Marta); España, A. (Agustín); Alzuguren, P. (Pilar); et al. "The involvement of ADAM10 in acantholysis in mucocutaneous pemphigus vulgaris depends on the autoantibody profile of each patient". British Journal of Dermatology. 182 (5), 2020, 1194 - 1204
Abstract
Background Acantholysis in pemphigus vulgaris (PV) may be triggered by desmoglein (Dsg) and non‐Dsg autoantibodies. The autoantibody profile of each patient results in distinct intracellular signalling patterns. Objectives Based on our previous findings, we aimed to elucidate whether PV acantholysis in a mouse model may be mediated by activation of a disintegrin and metalloproteinase 10 (ADAM10). Methods We used three PV‐IgG fractions from different patients containing high or low levels of anti‐Dsg1 and anti‐Dsg3 antibodies, and the presence or not of anti‐desmocollin (Dsc) antibodies, using a passive transfer mouse model of PV. Results Although all of the PV‐IgG fractions produced suprabasal acantholysis, only those containing anti‐Dsg1/3, but not anti‐Dsc2/3 antibodies, induced ADAM10 activation in a Src‐dependent way, and an increase in the epidermal growth factor (EGF) receptor ligands EGF and betacellulin (BTC). In contrast, the presence of anti‐Dsc2/3 antibodies, in addition to anti‐Dsg1/3, triggered earlier and ADAM10‐independent epidermal detachment, with no increase in EGF and BTC, which was associated with an earlier and more intense acantholysis. Conclusions All PV‐IgG fractions produced suprabasal acantholysis, but our results reveal that depending on the levels of anti‐Dsg antibodies or the presence of non‐Dsg antibodies, such as anti‐Dsc, more severe cell–cell epidermal detachment will occur at different times, and in an ADAM10‐dependent manner or not. Acantholysis in these different groups of patients with PV may be a consequence of the activation of specific intracellular mechanisms downstream of Autoantibodies binding to Dsg or non‐Dsg proteins, and therefore more specific therapeutic approaches in PV should be used.

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