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United European Gastroenterol J. 2018 Aug;6(7):1074-1081. doi: 10.1177/2050640618774637. Epub 2018 May 02.

An increased Bax/Bcl-2 ratio in circulating inflammatory cells predicts primary response to infliximab in inflammatory bowel disease patients.

United European gastroenterology journal

Hamid Asadzadeh Aghdaei, Azade Amini Kadijani, Dario Sorrentino, Alireza Mirzaei, Shabnam Shahrokh, Hedieh Balaii, Marco Geraci, Mohammad Reza Zali

Affiliations

  1. Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
  2. IBD Center, Virginia Tech Carilion School of Medicine, Roanoke, VA, USA.
  3. Department of Clinical and Experimental Medical Sciences, University of Udine School of Medicine, Udine, Italy.
  4. Bone and Joint Reconstruction Research Center, Shafa Orthopedic Hospital, Iran University of Medical Sciences, Tehran, Iran.
  5. Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, Columbia, SC, USA.
  6. Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

PMID: 30228896 PMCID: PMC6137581 DOI: 10.1177/2050640618774637

Abstract

BACKGROUND: Predicting the response of inflammatory bowel disease (IBD) patients to infliximab (IFX) is an unmet clinical need. The expression and density of transmembrane tumor necrosis factor-α in circulating leukocytes maybe directly related to response by promoting apoptosis.

AIM: We tested the hypothesis that direct apoptosis assessment by real-time polymerase chain reaction evaluation of pro-apoptotic (Bax) and anti-apoptotic (Bcl-2) proteins in peripheral blood mononuclear cells (PBMCs) might be associated with response to IFX.

METHODS: IFX naïve patients (Crohn's disease, 32 and ulcerative colitis, 20; 35 responders and 17 non-responders) were evaluated for Bax and Bcl-2 mRNA expression levels before and 2 weeks after the first infusion. In a subset of patients, apoptosis was also evaluated using flow cytometry.

RESULTS: After the first infusion, Bax increased more in responders than in non-responders (0.7± 0.38 vs 0.81 ± 0.32 and 0.86 ± 0.37 vs 0.87 ± 0.45, respectively,

CONCLUSIONS: An increased Bax/Bcl-2 ratio in PBMCs was associated with therapeutic response to IFX in IBD patients.

Keywords: Apoptosis; inflammatory bowel diseases; infliximab; therapeutic response

References

  1. Gut. 2004 Nov;53(11):1632-8 - PubMed
  2. Clin Transl Gastroenterol. 2017 Sep 14;8(9):e117 - PubMed
  3. Nat Rev Rheumatol. 2014 Oct;10(10):612-27 - PubMed
  4. Proc Natl Acad Sci U S A. 2000 Jan 18;97(2):529-31 - PubMed
  5. Iran Biomed J. 2015;19(2):69-75 - PubMed
  6. Jpn J Clin Oncol. 2004 Mar;34(3):124-30 - PubMed
  7. Gut. 2004 Nov;53(11):1624-31 - PubMed
  8. BMJ. 2017 Jun 19;357:j2505 - PubMed
  9. Leukemia. 1996 Jul;10 Suppl 3:S18-S22 - PubMed
  10. Gastroenterology. 2011 May;140(6):1817-1826.e2 - PubMed
  11. Aliment Pharmacol Ther. 2011 Jul;34(1):1-10 - PubMed
  12. Aliment Pharmacol Ther. 2011 May;33(9):987-95 - PubMed
  13. Nat Protoc. 2008;3(6):1101-8 - PubMed
  14. Expert Rev Pharmacoecon Outcomes Res. 2014 Dec;14(6):815-24 - PubMed
  15. In Vivo. 2007 Jan-Feb;21(1):123-32 - PubMed
  16. Gastroenterology. 2001 Nov;121(5):1242-6 - PubMed
  17. Gut. 2004 Jan;53(1):70-7 - PubMed
  18. Gastroenterology. 2007 Feb;132(2):763-86 - PubMed
  19. Am J Gastroenterol. 2009 Mar;104(3):760-7 - PubMed
  20. Gastroenterology. 2001 Nov;121(5):1145-57 - PubMed
  21. Gastroenterology. 2003 Jun;124(7):1774-85 - PubMed
  22. J Immunol. 2006 Feb 15;176(4):2617-24 - PubMed
  23. BMC Immunol. 2016 Mar 15;17:6 - PubMed
  24. J Crohns Colitis. 2013 Oct;7(9):706-16 - PubMed
  25. Gut. 2007 Apr;56(4):509-17 - PubMed
  26. Dig Liver Dis. 2008 Jul;40 Suppl 2:S225-8 - PubMed
  27. Front Immunol. 2015 Nov 02;6:551 - PubMed
  28. Inflamm Bowel Dis. 2014 Oct;20(10):1850-61 - PubMed
  29. Therap Adv Gastroenterol. 2009 Jul;2(4):245-51 - PubMed
  30. Gut. 2016 Aug;65(8):1261-8 - PubMed
  31. Clin Exp Rheumatol. 2008 Mar-Apr;26(2):234-9 - PubMed
  32. Curr Pharm Des. 2014;20(7):1082-96 - PubMed
  33. Arthritis Rheum. 2008 May;58(5):1248-57 - PubMed
  34. Gut. 2007 Feb;56(2):293-303 - PubMed
  35. Dis Markers. 2014;2014:836082 - PubMed
  36. Cell. 1993 Aug 27;74(4):609-19 - PubMed
  37. Cytokine. 1995 Apr;7(3):251-9 - PubMed
  38. Gut. 2002 Feb;50(2):206-11 - PubMed

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