Neutrophil/lymphocyte ratio and lymphocyte/monocyte ratio in ulcerative colitis as non-invasive biomarkers of disease activity and severity

Ashraf M Okba, Mariam M Amin, Ahmed S Abdelmoaty, Hend E Ebada, Amgad H Kamel, Ahmed S Allam, Omar M Sobhy, Ashraf M Okba, Mariam M Amin, Ahmed S Abdelmoaty, Hend E Ebada, Amgad H Kamel, Ahmed S Allam, Omar M Sobhy

Abstract

Background: Apart from endoscopic interventions, readily attainable cost-effective biomarkers for ulcerative colitis (UC) assessment are required. For this purpose, we evaluated differential leucocytic ratio, mainly neutrophil-lymphocyte ratio (NLR) and lymphocyte-monocyte ratio (LMR) as simple available indicators of disease activity in patients with ulcerative colitis.

Methods: Study conducted on 80 UC patients who were classified into two groups of 40 each according to Mayo score and colonoscopic findings. Group 1 (active UC) and group 2 (inactive UC). Another 40 group-matched healthy participants were enrolled. White blood cell count, NLR, LMR, C-reactive protein, and Erythrocyte sedimentation rate were measured and recorded.

Results: Significant elevation of NLR was observed in active UC group compared to inactive UC and controls (2.63 ± 0.43, 1.64 ± 0.25, 1.44 ± 0.19 respectively; p < 0.0001). The optimal NLR cut-off value for active UC was > 1.91, with a sensitivity and a specificity of 90% and 90% respectively. The mean LMRs of active UC was significantly lower compared with inactive UC patients and controls (2.25 ± 0.51, 3.58 ± 0.76, 3.64 ± 0.49 respectively; p < 0.0001). The cut-off value of LMR for determining the disease activity was ≤ 2.88 with a sensitivity of 90% and a specificity of 90%. NLR, LMR, and CRP were found to be significant independent markers for discriminating disease activity (p = 0.000). Besides, NLR was significantly higher in patients with pancolitis and positively correlated with endoscopically severe disease.

Conclusion: NLRs and LMRs are simple non-invasive affordable independent markers of disease activity in UC.

Keywords: Disease activity; Monocyte–lymphocyte ratio; Neutrophil–lymphocyte ratio; Ulcerative colitis.

Conflict of interest statement

The authors declare that they have no competing interests.

© The Author(s) 2019.

References

    1. El-Kheshen G, Moeini M, Saadat M. Susceptibility to ulcerative colitis and genetic polymorphisms of A251G SOD1 and C-262T CAT. J Med Biochem. 2016;35:333–336. doi: 10.1515/jomb-2016-0002.
    1. DeRoche TC, Xiao SY, Liu X. Histological evaluation in ulcerative colitis. Gastroenterol Rep (Oxf) 2014;2:178–192. doi: 10.1093/gastro/gou031.
    1. Nakarai A, Kato J, Hiraoka S, Nakarai A, Takei D, Inokuchi T, et al. Evaluation of mucosal healing of ulcerative colitis by a quantitative fecal immunochemical test. Am J Gastroenterol. 2013;108:83–89. doi: 10.1038/ajg.2012.315.
    1. Schoepfer AM, Beglinger C, Straumann A, Trummler M, Renzulli P, Seibold F. Ulcerative colitis: correlation of the Rachmilewitz endoscopic activity index with fecal calprotectin, clinical activity, C-reactive protein, and blood leukocytes. Inflamm Bowel Dis. 2009;15(12):1851–1858. doi: 10.1002/ibd.20986.
    1. Solem CA, Loftus EV, Jr, Tremaine WJ, Harmsen WS, Zinsmeister AR, Sandborn WJ. Correlation of C-reactive protein with clinical, endoscopic, histologic, and radiographic activity in inflammatory bowel disease. Inflamm Bowel Dis. 2005;11(8):707–712. doi: 10.1097/01.MIB.0000173271.18319.53.
    1. Lewis JD. The utility of biomarkers in the diagnosis and therapy of inflammatory bowel disease. Gastroenterology. 2011;140:1817–1826. doi: 10.1053/j.gastro.2010.11.058.
    1. Schoepfer AM, Beglinger C, Straumann A, Safroneeva E, Romero Y, Armstrong D, et al. Fecal calprotectin more accurately reflects endoscopic activity of ulcerative colitis than the Lichtiger Index, C-reactive protein, platelets, hemoglobin, and blood leukocytes. Inflamm Bowel Dis. 2013;19(2):332–341. doi: 10.1097/MIB.0b013e3182810066.
    1. Lester SE, Proudman SM, Lee AT, Hall SA, McWilliams L, James LJ, et al. Treatment-induced stable, moderate reduction in blood cell counts correlate to disease control in early rheumatoid arthritis. Intern Med J. 2009;39:296–303. doi: 10.1111/j.1445-5994.2008.01737.x.
    1. Huang G, Zhong XN, Zhong B, Chen YQ, Liu ZZ, Su L, et al. Significance of white blood cell count and its subtypes in patients with acute coronary syndrome. Eur J Clin Invest. 2009;39:348–358. doi: 10.1111/j.1365-2362.2009.02107.x.
    1. Thayer WR, Jr, Charland C, Field CE. The subpopulations of circulating white blood cells in inflammatory bowel disease. Gastroenterology. 1976;71(3):379–384. doi: 10.1016/S0016-5085(76)80439-8.
    1. Mee AS, Berney J, Jewell DP. Monocytes in inflammatory bowel disease: absolute monocyte counts. J Clin Pathol. 1980;33(10):917–920. doi: 10.1136/jcp.33.10.917.
    1. Wallace KL, Zheng LB, Kanazawa Y, Shih DQ. Immunopathology of inflammatory bowel disease. World J Gastroenterol. 2014;20(1):6–21. doi: 10.3748/wjg.v20.i1.6.
    1. Xue TC, Zhang L, Xie XY, Ge NL, Li LX, Zhang BH, et al. Prognostic significance of the neutrophil-to-lymphocyte ratio in primary liver cancer: a meta-analysis. PLoS ONE. 2014;9:960–972.
    1. Gokmen F, Akbal A, Resorlu H, Gökmen E, Güven M, Aras AB, et al. Neutrophil–lymphocyte ratio connected to treatment options and inflammation markers of ankylosing spondylitis. J Clin Lab Anal. 2015;29:294–298. doi: 10.1002/jcla.21768.
    1. Li MX, Liu XM, Zhang XF, Zhang JF, Wang WL, Zhu Y, et al. Prognostic role of neutrophil-to-lymphocyte ratio in colorectal cancer: a systematic review and meta-analysis. Int J Cancer. 2014;134:2403–2413. doi: 10.1002/ijc.28536.
    1. McNamara MG, Templeton AJ, Maganti M, Walter T, Horgan AM, McKeever L, et al. Neutrophil/lymphocyte ratio as a prognostic factor in biliary tract cancer. Eur J Cancer. 2014;50:1581–1589. doi: 10.1016/j.ejca.2014.02.015.
    1. Posul E, Yilmaz B, Aktas G, Kurt M. Does neutrophil-to-lymphocyte ratio predict active ulcerative colitis? Wien Klin Wochenschr. 2015;127:262–265. doi: 10.1007/s00508-014-0683-5.
    1. Demir AK, Demirtas A, Kaya SU, Tastan I, Butun I, Sagcan M, et al. The relationship between the neutrophilelymphocyte ratio and disease activity in patients with ulcerative colitis. Kaohsiung J Med Sci. 2015;31:585–590. doi: 10.1016/j.kjms.2015.10.001.
    1. Cherfane CE, Gessel L, Cirillo D. Monocytosis and a low lymphocyte to monocyte ratio are effective biomarkers of ulcerative colitis disease activity. Inflamm Bowel Dis. 2015;21(8):1769–1775. doi: 10.1097/MIB.0000000000000427.
    1. Lewis JD, Chuai S, Nessel L, Lichtenstein GR, Aberra FN, Ellenberg JH. Use of the noninvasive components of the Mayo score to assess clinical response in ulcerative colitis. Inflamm Bowel Dis. 2008;14:1660–1666. doi: 10.1002/ibd.20520.
    1. Henderson AR. Assessing test accuracy and its clinical consequences: a primer for receiver operating characteristic curve analysis. Ann Clin Biochem. 1993;30:521–539. doi: 10.1177/000456329303000601.
    1. Makkar R, Bo S. Colonoscopic perforation in inflammatory bowel disease. Gastroenterol Hepatol. 2013;9:573–583.
    1. Rutka M, Milassin Á, Szepes Z, SzŰcs M, Nyári T, Bálint A, et al. Is mucosal healing more common than clinical remission in ulcerative colitis? Is it the truth or only a myth coming from the studies? Scand J Gastroenterol. 2015;50:985–990. doi: 10.3109/00365521.2015.1018313.
    1. Vermeire S, Van Assche G, Rutgeerts P. Laboratory markers in IBD: useful, magic, or unnecessary toys? Gut. 2006;55:426–431. doi: 10.1136/gut.2005.069476.
    1. Van Rheenen PF, Van de Vijver E, Fidler V. Faecal calprotectin for screening of patients with suspected inflammatory bowel disease: diagnostic meta-analysis. BMJ. 2010;341:c3369. doi: 10.1136/bmj.c3369.
    1. Langhorst J, Elsenbruch S, Koelzer J, Rueffer A, Michalsen A, Dobos GJ. Non-invasive markers in the assessment of intestinal inflammation in inflammatory bowel diseases: performance of fecal lactoferrin, calprotectin, and PMN-elastase, CRP, and clinical indices. Am J Gastroenterol. 2008;103:162–169. doi: 10.1111/j.1572-0241.2007.01556.x.
    1. Torun S, Tunc BD, Suvak B, Yildiz H, Tas A, Sayilir A, et al. Assessment of neutrophil lymphocyte ratio in ulcerative colitis: a promising marker in predicting disease severity. Clin Res Hepatol Gastroenterol. 2012;3:491–497. doi: 10.1016/j.clinre.2012.06.004.
    1. Akpinar M, Ozin Y, Kaplan M, Ates I, Kalkan I, Kilic Z, Yuksel M, Kayacetin E. Platelet-to-lymphocyte ratio and neutrophil-to-lymphocyte ratio predict mucosal disease severity in ulcerative colitis. J Med Biochem. 2018;37:155–162. doi: 10.1515/jomb-2017-0050.
    1. Macdonald TT, Monteleone I, Fantini MC, Monteleone G. Regulation of homeostasis and inflammation in the intestine. Gastroenterology. 2011;140:1768–1775. doi: 10.1053/j.gastro.2011.02.047.
    1. Nixon J, Riddell R. Histopathology in ulcerative colitis. In: Allan R, Keighley M, Alexander-Williams C, Hawkins C, editors. Inflammatory bowel disease. Edinburgh: Churchill Livingstone; 1990. pp. 247–285.
    1. Hermanowicz A, Gibson PR, Jewell DP. The role of phagocytes in inflammatory bowel disease. Clin Sci (Lond) 1985;69:41–49. doi: 10.1042/cs0690241.
    1. Sachar DB, Taub RN, Brown SM, Present DH, Korelitz BI, Janowitz HD. Imparied lymphocyte responsiveness in inflammatory bowel disease. Gastroenterology. 1973;64:203–209. doi: 10.1016/S0016-5085(73)80178-7.
    1. Avanzas P, Quiles J, de Sa EL, Sanchez A, Rubio R, García E, et al. Neutrophil count and infarct size in patients with acute myocardial infarction. Int J Cardiol. 2004;97:155–156. doi: 10.1016/j.ijcard.2003.06.028.
    1. Ommen SR, Hodge DO, Rodehefer RJ, McGregor CG, Thomson SP, Gibbons RJ. Predictive power of the relative lymphocyte concentration in patients with advanced heart failure. Circulation. 1998;97:19–22. doi: 10.1161/01.CIR.97.1.19.
    1. Rosenberg L, Lawlor GO, Zenlea T, Goldsmith JD, Gifford A, Falchuk KR, et al. Predictors of endoscopic inflammation in patients with ulcerative colitis in clinical remission. Inflamm Bowel Dis. 2013;19(4):779–784. doi: 10.1097/MIB.0b013e3182802b0e.
    1. Shi C, Pamer EG. Monocyte recruitment during infection and inflammation. Nat Rev Immunol. 2011;11:762–774. doi: 10.1038/nri3070.
    1. Celikbilek M, Dogan S, Ozbakır O, Zararsız G, Kücük H, Gürsoy S, et al. Neutrophil–lymphocyte ratio as a predictor of disease severity in ulcerative colitis. J Clin Lab Anal. 2013;27(1):72–76. doi: 10.1002/jcla.21564.

Source: PubMed

3
Subscribe