Altered plasma levels of the SARS-CoV-2-related proteins ACE2 and TMPRSS2 in patients with Crohn's disease

The SARS-CoV-2 coronavirus infects cells through the cellular receptor angiotensin-converting enzyme 2 (ACE2), and the protease TMPRSS2 for the priming of viral spike protein. Thus, changes in these key proteins due to chronic conditions can increase risk for SARS-CoV2 infection; but significance of...

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Detalhes bibliográficos
Autores: Sáez-Leyva, J, Lennol, MP, Avilés-Granados, C, García-Ayllón, MS, Gutiérrez, A, Francés, R, Saez-Valero, J
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Recursos:Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)
Repositorio:r-FISABIO. Repositorio Institucional de Producción Científica
OAI Identifier:oai:fisabio.fundanetsuite.com:p18320
Acesso em linha:https://fisabio.portalinvestigacion.com/publicaciones/18320
Access Level:acceso abierto
Palavra-chave:ACE2
Crohn's disease
Inflammatory bowel disease
Plasma
Biological therapy
TMPRSS2
Descrição
Resumo:The SARS-CoV-2 coronavirus infects cells through the cellular receptor angiotensin-converting enzyme 2 (ACE2), and the protease TMPRSS2 for the priming of viral spike protein. Thus, changes in these key proteins due to chronic conditions can increase risk for SARS-CoV2 infection; but significance of changes may differ is these changes correspond to full-length species or proteolytic fragments. Here, we determined that full-length ACE2 decreased in the plasma of uninfected Crohn's disease (CD) patients before treatment onset compared to controls. TMPRSS2 is mostly presented in plasma as full-length species and as an active peptidase fragment, but also as a prodomain fragment, which is the unique species remarkably decreased in plasma from CD patients. Patients treated with the anti-TNF alpha adalimumab showed recovery in ACE2 levels, while those treated with infliximab, or with the anti-IL-12/23 ustekinumab, still displayed a decrease in full-length species, as well as in cleaved fragments. Patients treated with azathioprine displayed similar ACE2 levels to that of controls, except a decrease in one of the ACE2 fragments. Uniquely, patients treated with azathioprine or with ustekinumab showed partial recovery in the reduction of the TMPRSS2-prodomain fragment characterized in treatment-na & iuml;ve patients. Our data suggest that CD and common therapies are not related to increased susceptibility for SARS-CoV-2.