tetano
Editor, Senior Moderator
Sci Rep
. 2024 Dec 5;14(1):30346.
doi: 10.1038/s41598-024-81810-3. Altered plasma levels of the SARS-CoV-2-related proteins ACE2 and TMPRSS2 in patients with Crohn's disease
Jorge Sáez-Leyva[SUP] #[/SUP][SUP] 1 2 [/SUP], Matthew P Lennol[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Carlos Avilés-Granados[SUP] 1 2 4 [/SUP], María-Salud García-Ayllón[SUP] 1 2 5 [/SUP], Ana Gutiérrez[SUP] 4 6 7 [/SUP], Rubén Francés[SUP] 8 9 10 [/SUP], Javier Sáez-Valero[SUP] 11 12 13 [/SUP]
Affiliations
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-TNFα 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-naïve patients. Our data suggest that CD and common therapies are not related to increased susceptibility for SARS-CoV-2.
Keywords: ACE2; Biological therapy; Crohn’s disease; Inflammatory bowel disease; Plasma; TMPRSS2.
. 2024 Dec 5;14(1):30346.
doi: 10.1038/s41598-024-81810-3. Altered plasma levels of the SARS-CoV-2-related proteins ACE2 and TMPRSS2 in patients with Crohn's disease
Jorge Sáez-Leyva[SUP] #[/SUP][SUP] 1 2 [/SUP], Matthew P Lennol[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Carlos Avilés-Granados[SUP] 1 2 4 [/SUP], María-Salud García-Ayllón[SUP] 1 2 5 [/SUP], Ana Gutiérrez[SUP] 4 6 7 [/SUP], Rubén Francés[SUP] 8 9 10 [/SUP], Javier Sáez-Valero[SUP] 11 12 13 [/SUP]
Affiliations
- PMID: 39638806
- PMCID: PMC11621418
- DOI: 10.1038/s41598-024-81810-3
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-TNFα 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-naïve patients. Our data suggest that CD and common therapies are not related to increased susceptibility for SARS-CoV-2.
Keywords: ACE2; Biological therapy; Crohn’s disease; Inflammatory bowel disease; Plasma; TMPRSS2.