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

• Published in: Scientific reports 2024-12, Vol.14 (1), p.30346-10
• Main Authors: Sáez-Leyva, Jorge, Lennol, Matthew P., Avilés-Granados, Carlos, García-Ayllón, María-Salud, Gutiérrez, Ana, Francés, Rubén, Sáez-Valero, Javier
• Format: Article
• Language: English
• Subjects: 631/45; 692/4020; 692/499; ACE2; Adult; Angiotensin; Angiotensin-converting enzyme 2; Angiotensin-Converting Enzyme 2 - blood; Angiotensin-Converting Enzyme 2 - metabolism; Azathioprine; Biochemistry, Molecular Biology; Biological therapy; Chronic infection; Coronaviruses; COVID-19; COVID-19 - blood; COVID-19 - virology; Crohn Disease - blood; Crohn Disease - drug therapy; Crohn Disease - virology; Crohn's disease; Female; Humanities and Social Sciences; Humans; Inflammatory bowel disease; Infliximab; Life Sciences; Male; Middle Aged; Molecular biology; Monoclonal antibodies; multidisciplinary; Peptidyl-dipeptidase A; Plasma; Plasma levels; Proteolysis; SARS-CoV-2; Science; Science (multidisciplinary); Serine Endopeptidases - blood; Serine Endopeptidases - metabolism; Severe acute respiratory syndrome coronavirus 2; Spike protein; TMPRSS2; Tumor necrosis factor-α
• ISSN: 2045-2322; 2045-2322
• 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.