Down-Regulation of Colonic ACE2 Expression in Patients With Inflammatory Bowel Disease Responding to Anti-TNF Therapy: Implications for COVID-19
Background and Aims: Angiotensin-converting enzyme II (ACE2) is the key molecule for understanding the pathophysiology of COVID-19. The risk of COVID-19 and impact of immunosuppressive treatment on disease course in patients with inflammatory bowel disease (IBD) remain controversial. We aimed to det...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-01-01
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| Series: | Frontiers in Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmed.2020.613475/full |
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| author | Xiao-Zhi Li Yun Qiu Louisa Jeffery Louisa Jeffery Fen Liu Rui Feng Jin-Shen He Jin-Yu Tan Zi-Yin Ye Si-Nan Lin Subrata Ghosh Subrata Ghosh Marietta Iacucci Marietta Iacucci Min-Hu Chen Ren Mao |
| author_facet | Xiao-Zhi Li Yun Qiu Louisa Jeffery Louisa Jeffery Fen Liu Rui Feng Jin-Shen He Jin-Yu Tan Zi-Yin Ye Si-Nan Lin Subrata Ghosh Subrata Ghosh Marietta Iacucci Marietta Iacucci Min-Hu Chen Ren Mao |
| author_sort | Xiao-Zhi Li |
| collection | DOAJ |
| description | Background and Aims: Angiotensin-converting enzyme II (ACE2) is the key molecule for understanding the pathophysiology of COVID-19. The risk of COVID-19 and impact of immunosuppressive treatment on disease course in patients with inflammatory bowel disease (IBD) remain controversial. We aimed to determine the change of intestinal ACE2 expression before and after biologics treatment including anti-tumor necrosis factor α (anti-TNFα), anti-integrin, and anti-interleukin (IL)12/23 in IBD patients.Methods: We analyzed the ACE2 expression through the public database of paired intestinal biopsies from IBD patients before and after biologic therapy. Change of ACE2 RNA and protein expression were validated in two independent cohorts (Birmingham cohort and Guangzhou cohort). The correlation between ACE2 expression and disease activity was also analyzed.Results: Mining information from the GEO database showed that compared with healthy control, intestinal ACE2 expression was downregulated in ileum of CD patients, while upregulated in colon of both CD and UC patients. Colonic ACE2 RNA expression was decreased significantly in patients responding to anti-TNFα but not anti-integrin and anti-IL12/23, which was validated in the Birmingham cohort. Using the Guangzhou cohort including 53 patients matched by pre- and post-anti-TNFα therapy, colonic ACE2 protein expression was significantly downregulated after anti-TNFα treatment in responders (P < 0.001) rather than non-responders. Colonic ACE2 expression was significantly higher in patients with severe histologically active disease compared with those with moderate (P < 0.0001) and mild (P = 0.0002) histologically active disease.Conclusion: Intestinal inflammation influences the expression of intestinal ACE2 in IBD patients, with different alterations in the ileum and colon. Colonic ACE2 expression was downregulated after anti-TNFα therapy in IBD patients responding to treatment. This might provide new clues regarding the risk of SARS-CoV-2 infection and the potential benefit of sustaining anti-TNFα treatment in patients with IBD. |
| first_indexed | 2024-12-19T10:51:21Z |
| format | Article |
| id | doaj.art-5da03e09728042b79c77c9bfcf303572 |
| institution | Directory Open Access Journal |
| issn | 2296-858X |
| language | English |
| last_indexed | 2024-12-19T10:51:21Z |
| publishDate | 2021-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Medicine |
| spelling | doaj.art-5da03e09728042b79c77c9bfcf3035722022-12-21T20:24:59ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2021-01-01710.3389/fmed.2020.613475613475Down-Regulation of Colonic ACE2 Expression in Patients With Inflammatory Bowel Disease Responding to Anti-TNF Therapy: Implications for COVID-19Xiao-Zhi Li0Yun Qiu1Louisa Jeffery2Louisa Jeffery3Fen Liu4Rui Feng5Jin-Shen He6Jin-Yu Tan7Zi-Yin Ye8Si-Nan Lin9Subrata Ghosh10Subrata Ghosh11Marietta Iacucci12Marietta Iacucci13Min-Hu Chen14Ren Mao15Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaDepartment of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaInstitute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United KingdomNational Institute for Health Research Biomedical Research Center, University of Birmingham and University Hospitals Birmingham NHS Foundation Trust, Birmingham, United KingdomDepartment of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaDepartment of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaDepartment of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaDepartment of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaDepartment of Pathology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaDepartment of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaInstitute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United KingdomNational Institute for Health Research Biomedical Research Center, University of Birmingham and University Hospitals Birmingham NHS Foundation Trust, Birmingham, United KingdomInstitute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United KingdomNational Institute for Health Research Biomedical Research Center, University of Birmingham and University Hospitals Birmingham NHS Foundation Trust, Birmingham, United KingdomDepartment of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaDepartment of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaBackground and Aims: Angiotensin-converting enzyme II (ACE2) is the key molecule for understanding the pathophysiology of COVID-19. The risk of COVID-19 and impact of immunosuppressive treatment on disease course in patients with inflammatory bowel disease (IBD) remain controversial. We aimed to determine the change of intestinal ACE2 expression before and after biologics treatment including anti-tumor necrosis factor α (anti-TNFα), anti-integrin, and anti-interleukin (IL)12/23 in IBD patients.Methods: We analyzed the ACE2 expression through the public database of paired intestinal biopsies from IBD patients before and after biologic therapy. Change of ACE2 RNA and protein expression were validated in two independent cohorts (Birmingham cohort and Guangzhou cohort). The correlation between ACE2 expression and disease activity was also analyzed.Results: Mining information from the GEO database showed that compared with healthy control, intestinal ACE2 expression was downregulated in ileum of CD patients, while upregulated in colon of both CD and UC patients. Colonic ACE2 RNA expression was decreased significantly in patients responding to anti-TNFα but not anti-integrin and anti-IL12/23, which was validated in the Birmingham cohort. Using the Guangzhou cohort including 53 patients matched by pre- and post-anti-TNFα therapy, colonic ACE2 protein expression was significantly downregulated after anti-TNFα treatment in responders (P < 0.001) rather than non-responders. Colonic ACE2 expression was significantly higher in patients with severe histologically active disease compared with those with moderate (P < 0.0001) and mild (P = 0.0002) histologically active disease.Conclusion: Intestinal inflammation influences the expression of intestinal ACE2 in IBD patients, with different alterations in the ileum and colon. Colonic ACE2 expression was downregulated after anti-TNFα therapy in IBD patients responding to treatment. This might provide new clues regarding the risk of SARS-CoV-2 infection and the potential benefit of sustaining anti-TNFα treatment in patients with IBD.https://www.frontiersin.org/articles/10.3389/fmed.2020.613475/fullCOVID-19ACE2inflammatory bowel diseaseintestineanti-TNFα |
| spellingShingle | Xiao-Zhi Li Yun Qiu Louisa Jeffery Louisa Jeffery Fen Liu Rui Feng Jin-Shen He Jin-Yu Tan Zi-Yin Ye Si-Nan Lin Subrata Ghosh Subrata Ghosh Marietta Iacucci Marietta Iacucci Min-Hu Chen Ren Mao Down-Regulation of Colonic ACE2 Expression in Patients With Inflammatory Bowel Disease Responding to Anti-TNF Therapy: Implications for COVID-19 Frontiers in Medicine COVID-19 ACE2 inflammatory bowel disease intestine anti-TNFα |
| title | Down-Regulation of Colonic ACE2 Expression in Patients With Inflammatory Bowel Disease Responding to Anti-TNF Therapy: Implications for COVID-19 |
| title_full | Down-Regulation of Colonic ACE2 Expression in Patients With Inflammatory Bowel Disease Responding to Anti-TNF Therapy: Implications for COVID-19 |
| title_fullStr | Down-Regulation of Colonic ACE2 Expression in Patients With Inflammatory Bowel Disease Responding to Anti-TNF Therapy: Implications for COVID-19 |
| title_full_unstemmed | Down-Regulation of Colonic ACE2 Expression in Patients With Inflammatory Bowel Disease Responding to Anti-TNF Therapy: Implications for COVID-19 |
| title_short | Down-Regulation of Colonic ACE2 Expression in Patients With Inflammatory Bowel Disease Responding to Anti-TNF Therapy: Implications for COVID-19 |
| title_sort | down regulation of colonic ace2 expression in patients with inflammatory bowel disease responding to anti tnf therapy implications for covid 19 |
| topic | COVID-19 ACE2 inflammatory bowel disease intestine anti-TNFα |
| url | https://www.frontiersin.org/articles/10.3389/fmed.2020.613475/full |
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