Evaluating the clinical application of the immune cells’ ratios and inflammatory markers in the diagnosis of inflammatory bowel disease
Main Article Content
Keywords
IBD, Crohn’s disease, Ulcerative colitis, immune cells, Inflammation, Biomarkers, Neutrophil-to-lymphocyte, Platelet-to-lymphocytes
Abstract
Objective: Inflammatory Bowel Diseases (IBDs) are chronic inflammatory conditions of the gastrointestinal tract, including Crohn’s disease (CD) and ulcerative colitis (UC). Developing methods for effective screening and diagnosis is extremely needed. Accordingly, this study aims to evaluate the potential of immune cells ratios in the diagnosis of IBD. Methods: This case-control study includes data from Jordan University Hospital (JUH) medical records for IBD patients with age- and gender-matched healthy controls. Results: This study included 46 participants, of which 56.52% had IBD, 54.35% were males, with insignificant differences in sex, age, and body mass index (BMI) between IBD patients and controls (p>0.05). In the CD group, the variables with the highest sensitivity and specificity (HSS) were neutrophil-to-lymphocyte (NLR) (75%, 80%) and platelet-to-lymphocytes (PLR) (75%, 90%), in UC group; mean corpuscular hemoglobin (MCH) (80%, 80%). In CD group, the combinations giving the HSS were PLR+NLR (76%, 90.9%), C-reactive protein (CRP)+PLR (76%, 90.9%), and CRP+NLR (73.07%, 90%). In UC group, the combinations giving the HSS were erythrocyte sedimentation rate (ESR)+PLR (76.9%, 100%), PLR+MCH (74.07%, 100%), PLR+CRP (71.42%, 100%), and PLR+NLR (71.42%, 100%). Regression analysis identified five different combinations of significance in the diagnosis of CD and UC. Higher Youden’s index was used and defined the most beneficial clinical combinations as NLR+PLR and CRP+PLR for CD, whereas ESR+PLR for UC. Conclusion: Implications to our study include the clinical application of immune cell ratios, inflammatory markers, and their different combinations along with patients’ history and physical examination findings for easier, faster, and more cost-effective diagnosis of IBDs.
References
Hepatology. 2020;5(1):17-30. https://doi.org/10.1016/S2468-1253(19)30333-4
2. Greuter T, Vavricka S, König AO, et al. Malignancies in Inflammatory Bowel Disease. Digestion. 2020;101 Suppl 1:136-145. https://doi.org/10.1159/000509544
3. Guan Q. A Comprehensive Review and Update on the Pathogenesis of Inflammatory Bowel Disease. Journal of Immunology Research. 2019;2019:7247238. https://doi.org/10.1155/2019/7247238
4. Cupi ML, Sarra M, Marafini I, et al. Plasma cells in the mucosa of patients with inflammatory bowel disease produce granzyme B and possess cytotoxic activities. Journal of Immunology (Baltimore, Md. : 1950). 2014;192(12):6083-6091. https://doi.
org/10.4049/jimmunol.1302238
5. Furrie E, Macfarlane S, Cummings JH, et al. Systemic antibodies towards mucosal bacteria in ulcerative colitis and Crohn’s disease differentially activate the innate immune response. Gut. 2004;53(1):91-98. https://doi.org/10.1136/gut.53.1.91
6. Giuffrida P, Corazza GR, Di Sabatino A. Old and New Lymphocyte Players in Inflammatory Bowel Disease. Digestive Diseases and Sciences. 2018;63(2):277-288. https://doi.org/10.1007/s10620-017-4892-4
7. Jain U, Otley AR, Van Limbergen J, et al. The complement system in inflammatory bowel disease. Inflammatory bowel diseases. 2014;20:1628-1637. https://doi.org/10.1097/mib.0000000000000056
8. Lu Y, Li X, Liu S, et al. Toll-like Receptors and Inflammatory Bowel Disease. Frontiers in Immunology. 2018;9:72. https://doi.org/10.3389/fimmu.2018.00072
9. Na YR, Stakenborg M, Seok SH, et al. Macrophages in intestinal inflammation and resolution: a potential therapeutic target in IBD. Nature reviews. Gastroenterology & Hepatology. 2019;16(9):531-543. https://doi.org/10.1038/s41575-019-0172-4
10. Williams IR, Parkos CA. Colonic neutrophils in inflammatory bowel disease: double-edged swords of the innate immune system with protective and destructive capacity. Gastroenterology. 2007;133(6):2049-2052. https://doi.org/10.1053/j.
gastro.2007.10.031
11. Pithadia AB, Jain S. Treatment of inflammatory bowel disease (IBD). Pharmacological reports : PR. 2011;63:629-642.
12. Takeshima F, Matsumura M, Makiyama K, et al. Efficacy of long-term 4.0 g/day mesalazine (Pentasa) for maintenance therapy in ulcerative colitis. Medical science monitor: international Medical Journal of Experimental and Clinical Research. 2014;20:1314-
1318. https://doi.org/10.12659/MSM.890567
13. Papamichael K, Lin S, Moore M, et al. Infliximab in inflammatory bowel disease. Therapeutic Advances in Chronic Disease. 2019;10:2040622319838443.
14. Lewis RT, Maron DJ. Efficacy and complications of surgery for Crohn’s disease. Gastroenterology & hepatology. 2010;6(9):587- 596.
15. Billiet T, Ferrante M, Van Assche G. The use of prognostic factors in inflammatory bowel diseases. Current Gastroenterology Reports. 2014;16(11):416. https://doi.org/10.1007/s11894-014-0416-y
16. Chen Y, Chen K, Xiao X, et al. Pretreatment neutrophil-to-lymphocyte ratio is correlated with response to neoadjuvant chemotherapy as an independent prognostic indicator in breast cancer patients: a retrospective study. BMC cancer.
2016;16:320. https://doi.org/10.1186/s12885-016-2352-8
17. Acarturk G, Acay A, Demir K, et al. Neutrophil-to-lymphocyte ratio in inflammatory bowel disease - as a new predictor of disease severity. Bratislavske lekarske listy. 2015;116(4):213-217. https://doi.org/10.4149/bll_2015_041
18. Dell’Aquila E, Cremolini C, Zeppola T, et al. Prognostic and predictive role of neutrophil/lymphocytes ratio in metastatic colorectal cancer: a retrospective analysis of the TRIBE study by GONO. Annals of oncology : official Journal of the European
Society for Medical Oncology. 2018;29(4):924-930. https://doi.org/10.1093/annonc/mdy004
19. Farah R, Khamisy-Farah R. Association of neutrophil to lymphocyte ratio with presence and severity of gastritis due to Helicobacter pylori infection. Journal of Clinical Laboratory Analysis. 2014;28(3):219-223. https://doi.org/10.1002/jcla.21669
20. Hsu YC, Yang YY, Tsai IT. Lymphocyte-to-monocyte ratio predicts mortality in cirrhotic patients with septic shock. The American Journal of Emergency Medicine. 2021;40:70-76. https://doi.org/10.1016/j.ajem.2020.11.07
21. Jimeno S, Ventura PS, Castellano JM, et al. Prognostic implications of neutrophil-lymphocyte ratio in COVID-19. European Journal of Clinical Investigation. 2021;51(1):e13404. https://doi.org/10.1111/eci.13404
22. Murakami Y, Saito H, Shimizu S, et al. Neutrophil-to-Lymphocyte Ratio as a Prognostic Indicator in Patients With Unresectable Gastric Cancer. Anticancer Research. 2019;39(5):2583-2589. https://doi.org/10.21873/anticanres.13381
23. Zhen Y, Zhang H. NLRP3 Inflammasome and Inflammatory Bowel Disease. Frontiers in Immunology. 2019;10:276. https://doi.org/10.3389/fimmu.2019.00276
24. Demir AK, Demirtas A, Kaya SU, et al. The relationship between the neutrophil-lymphocyte ratio and disease activity in patients with ulcerative colitis. The Kaohsiung Journal of Medical Sciences. 2015;31(11):585-590. https://doi.org/10.1016/j.
kjms.2015.10.001
25. Akpinar MY, Ozin YO, Kaplan M, et al. Platelet-to-lymphocyte Ratio and Neutrophil-to-lymphocyte Ratio Predict Mucosal Disease Severity in Ulcerative Colitis. Journal of Medical Biochemistry. 2018;37(2):155-162. https://doi.org/10.1515/jomb-
2017-0050
26. Feng JR, Qiu X, Wang F, et al. Diagnostic Value of Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio in Crohn’s Disease. Gastroenterology Research and Practice. 2017;2017:3526460. https://doi.org/10.1155/2017/3526460
27. Feng J-R, Qiu X, Wang F, et al. Diagnostic value of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in Crohn’s disease. Gastroenterology Research and Practice. 2017;2017. https://doi.org/10.1155/2017/3526460
28. Demir AK, Demirtas A, Kaya SU, et al. The relationship between the neutrophil–lymphocyte ratio and disease activity in patients with ulcerative colitis. The Kaohsiung Journal of Medical Sciences. 2015;31(11):585-590. https://doi.org/10.1016/j.
kjms.2015.10.001
29. Acarturk G, Acay A, Demir K, et al. Neutrophil-to-lymphocyte ratio in inflammatory bowel disease-as a new predictor of disease severity. Bratislavske lekarske listy. 2015;116(4):213-217. https://doi.org/10.4149/bll_2015_041
30. Okba AM, Amin MM, Abdelmoaty AS, et al. Neutrophil/lymphocyte ratio and lymphocyte/monocyte ratio in ulcerative colitis as non-invasive biomarkers of disease activity and severity. Auto Immun Highlights. 2019;10(1):4. https://doi.org/10.1186/
s13317-019-0114-8
31. Jeong Y, Jeon SR, Kim HG, et al. The role of platelet to lymphocyte ratio and neutrophil to lymphocyte ratio in ulcerative colitis. Intestinal Research. 2021;19(1):62-70. https://doi.org/10.5217/ir.2019.09156
32. Hanafy AS, Monir MH, Abdel Malak H, et al. A Simple Noninvasive Score Predicts Disease Activity and Deep Remission in Ulcerative Colitis. Inflammatory Intestinal Diseases. 2018;3(1):16-24. https://doi.org/10.1159/000490795
33. Celikbilek M, Dogan S, Ozbakır O, et al. Neutrophil-lymphocyte ratio as a predictor of disease severity in ulcerative colitis. Journal of Clinical Laboratory Analysis. 2013;27(1):72-76. https://doi.org/10.1002/jcla.21564
34. Narula N, Wong ECL, Colombel JF, et al. Predicting endoscopic remission in Crohn’s disease by the modified multiplier SES-CD (MM-SES-CD). Gut. 2022;71(6):1078-1087. https://doi.org/10.1136/gutjnl-2020-323799
35. Torun S, Tunc BD, Suvak B, et al. Assessment of neutrophil-lymphocyte ratio in ulcerative colitis: a promising marker in predicting disease severity. Clinics and Research in Hepatology and Gastroenterology. 2012;36(5):491-497. https://doi.org/10.1016/j.
clinre.2012.06.00
36. Wlodarczyk MK, Sobolewska AE, Stec-Michalska K, et al. Neutrophil-lymphocyte ratio in Crohn’s disease patients predicts sustained response to infliximab 52-week therapy. Journal of Gastrointestinal and Liver Diseases : JGLD. 2015;24(1):127-128.