Abstract
Background: Neutrophil to lymphocyte ratio (NLR) is a marker for many inflammatory diseases. Ankylosing spondylitis (AS) is among these inflammatory diseases, and many studies have compared the NLR ratio between patients with AS and healthy controls.
Aim: This study aims to systematically review and analyze the available evidence about the significance of NLR values in AS.
Method: Based on Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines, we searched Embase, Pubmed, ISI Web of Science, and Scopus databases from inception to August 2020 using (“Ankylosing spondyl* ” OR “Bechterew Disease” OR “Rheumatoid Spondylitis”) AND ((neutrophil* AND lymphocyte*) OR NLR) as key terms of the search strategy. Data selection and extraction were conducted separately by two authors. We appraised the included articles according to the Joanna Briggs checklist. Comprehensive Meta-analysis Version 2 was used for analysis and assessment of publication bias. I2 > 75% and p-value < 0.05 were considered significant.
Result: In total, 182 studies resulted from a search in all databases. Duplicate removal, title, abstract, and full-text screening yielded 12 related studies, with 11 included in the meta-analysis. Quality assessment was satisfying in all studies. Pooled difference in NLR means value between patients and controls was 0.38 (95% CI: 0.24-0.52, p-value <0.0001). An I2 of 51% and a Cochran Q test p-value of <0.05 indicated moderate heterogeneity; thus, subgroup analysis had no indication. Publication bias was not significant (Funnel plot with an Egger’s intercept of -0.07; p-value=0.95).
Conclusion: Significant higher amounts of NLR may be strongly indicative of underlying inflammation in AS.
Keywords: Neutrophil to lymphocyte ratio, ankylosing spondylitis, inflammation marker, MOOSE, chronic inflammatory disease, immune response.
Graphical Abstract
[1]
Chang CC, Chang CW, Nguyen PA, et al. Ankylosing spondylitis and the risk of cancer. Oncol Lett 2017; 14(2): 1315-22.
[http://dx.doi.org/10.3892/ol.2017.6368] [PMID: 28789346]
[http://dx.doi.org/10.3892/ol.2017.6368] [PMID: 28789346]
[2]
Kucuk A, Uslu AU, Ugan Y, et al. Neutrophil-to-lymphocyte ratio is involved in the severity of ankylosing spondylitis. Bratisl Lek Listy 2015; 116(12): 722-5.
[http://dx.doi.org/10.4149/BLL_2015_142] [PMID: 26924141]
[http://dx.doi.org/10.4149/BLL_2015_142] [PMID: 26924141]
[3]
Dean LE, Jones GT, MacDonald AG, Downham C, Sturrock RD, Macfarlane GJ. Global prevalence of ankylosing spondylitis. Rheumatology (Oxford) 2014; 53(4): 650-7.
[http://dx.doi.org/10.1093/rheumatology/ket387] [PMID: 24324212]
[http://dx.doi.org/10.1093/rheumatology/ket387] [PMID: 24324212]
[4]
Bozan N, Alpayci M, Aslan M, Cankaya H, Kiroglu AF, Turan M, et al. Mean platelet volume, red cell distribution width, platelet-to-lymphocyte and neutrophil-to-lymphocyte ratios in patients with ankylosing spondylitis and their relationships with high-frequency hearing thresholds. European archives of oto-rhino-laryngology: official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS): affiliated with the German Society for Oto-Rhino-Laryngology -. Head Neck Surg 2016; 273(11): 3663-72.
[5]
Coşkun BN, Öksüz MF, Ermurat S, et al. Neutrophil lymphocyte ratio can be a valuable marker in defining disease activity in patients who have started anti-tumor necrosis factor (TNF) drugs for ankylosing spondylitis. Eur J Rheumatol 2014; 1(3): 101-5.
[http://dx.doi.org/10.5152/eurjrheumatol.2014.034] [PMID: 27708888]
[http://dx.doi.org/10.5152/eurjrheumatol.2014.034] [PMID: 27708888]
[6]
Huang JC, Qian BP, Qiu Y, et al. Quality of life and correlation with clinical and radiographic variables in patients with ankylosing spondylitis: a retrospective case series study. BMC Musculoskelet Disord 2017; 18(1): 352.
[http://dx.doi.org/10.1186/s12891-017-1711-1] [PMID: 28810915]
[http://dx.doi.org/10.1186/s12891-017-1711-1] [PMID: 28810915]
[7]
Wang DM, Zeng QY, Chen SB, Gong Y, Hou ZD, Xiao ZY. Prevalence and risk factors of osteoporosis in patients with ankylosing spondylitis: a 5-year follow-up study of 504 cases. Clin Exp Rheumatol 2015; 33(4): 465-70.
[PMID: 25962324]
[PMID: 25962324]
[8]
Boyraz I, Koç B, Boyacı A, Tutoğlu A, Sarman H, Ozkan H. Ratio of neutrophil/lymphocyte and platelet/lymphocyte in patient with ankylosing spondylitis that are treating with anti-TNF. Int J Clin Exp Med 2014; 7(9): 2912-5.
[PMID: 25356158]
[PMID: 25356158]
[9]
Imtiaz F, Shafique K, Mirza SS, Ayoob Z, Vart P, Rao S. Neutrophil lymphocyte ratio as a measure of systemic inflammation in prevalent chronic diseases in Asian population. Int Arch Med 2012; 5(1): 2.
[http://dx.doi.org/10.1186/1755-7682-5-2] [PMID: 22281066]
[http://dx.doi.org/10.1186/1755-7682-5-2] [PMID: 22281066]
[10]
Inal EE, Sunar I. SARATAŞ Ş, EROĞLU P, Salih İ, Yener M. May neutrophil-lymphocyte and platelet-lymphocyte ratios indicate disease activity in ankylosing spondylitis? Arch Rheumatol 2015; 30(2): 130-7.
[http://dx.doi.org/10.5606/ArchRheumatol.2015.4837]
[http://dx.doi.org/10.5606/ArchRheumatol.2015.4837]
[11]
Gökmen F, Akbal A, Reşorlu H, et al. Neutrophil-lymphocyte ratio connected to treatment options and inflammation markers of ankylosing spondylitis. J Clin Lab Anal 2015; 29(4): 294-8.
[http://dx.doi.org/10.1002/jcla.21768] [PMID: 24849656]
[http://dx.doi.org/10.1002/jcla.21768] [PMID: 24849656]
[12]
Mercan R, Bitik B, Tufan A, et al. The association between neutrophil/lymphocyte ratio and disease activity in rheumatoid arthritis and ankylosing spondylitis. J Clin Lab Anal 2016; 30(5): 597-601.
[http://dx.doi.org/10.1002/jcla.21908] [PMID: 26666737]
[http://dx.doi.org/10.1002/jcla.21908] [PMID: 26666737]
[13]
Templeton AJ, McNamara MG, Šeruga B, et al. Prognostic role of neutrophil-to-lymphocyte ratio in solid tumors: a systematic review and meta-analysis. J Natl Cancer Inst 2014; 106(6): dju124.
[http://dx.doi.org/10.1093/jnci/dju124] [PMID: 24875653]
[http://dx.doi.org/10.1093/jnci/dju124] [PMID: 24875653]
[14]
Uslu AU, Küçük A, Şahin A, et al. Two new inflammatory markers associated with Disease Activity Score-28 in patients with rheumatoid arthritis: neutrophil-lymphocyte ratio and platelet-lymphocyte ratio. Int J Rheum Dis 2015; 18(7): 731-5.
[http://dx.doi.org/10.1111/1756-185X.12582] [PMID: 25900081]
[http://dx.doi.org/10.1111/1756-185X.12582] [PMID: 25900081]
[15]
Ershadinia N, Mortazavinia N, Babaniamansour S, Najafi-Nesheli M, Babaniamansour P, Aliniagerdroudbari E. The prevalence of autoimmune diseases in patients with multiple sclerosis: A cross-sectional study in Qom, Iran, in 2018. Curr J Neurol 2020; 19(3): 98.
[16]
Bhat T, Teli S, Rijal J, et al. Neutrophil to lymphocyte ratio and cardiovascular diseases: a review. Expert Rev Cardiovasc Ther 2013; 11(1): 55-9.
[http://dx.doi.org/10.1586/erc.12.159] [PMID: 23259445]
[http://dx.doi.org/10.1586/erc.12.159] [PMID: 23259445]
[17]
Tamhane UU, Aneja S, Montgomery D, Rogers E-K, Eagle KA, Gurm HS. Association between admission neutrophil to lymphocyte ratio and outcomes in patients with acute coronary syndrome. Am J Cardiol 2008; 102(6): 653-7.
[http://dx.doi.org/10.1016/j.amjcard.2008.05.006] [PMID: 18773982]
[http://dx.doi.org/10.1016/j.amjcard.2008.05.006] [PMID: 18773982]
[18]
Guthrie GJ, Charles KA, Roxburgh CS, Horgan PG, McMillan DC, Clarke SJ. The systemic inflammation-based neutrophil-lymphocyte ratio: experience in patients with cancer. Crit Rev Oncol Hematol 2013; 88(1): 218-30.
[http://dx.doi.org/10.1016/j.critrevonc.2013.03.010] [PMID: 23602134]
[http://dx.doi.org/10.1016/j.critrevonc.2013.03.010] [PMID: 23602134]
[19]
Walsh SR, Cook EJ, Goulder F, Justin TA, Keeling NJ. Neutrophil-lymphocyte ratio as a prognostic factor in colorectal cancer. J Surg Oncol 2005; 91(3): 181-4.
[http://dx.doi.org/10.1002/jso.20329] [PMID: 16118772]
[http://dx.doi.org/10.1002/jso.20329] [PMID: 16118772]
[20]
Sarraf KM, Belcher E, Raevsky E, Nicholson AG, Goldstraw P, Lim E. Neutrophil/lymphocyte ratio and its association with survival after complete resection in non-small cell lung cancer. J Thorac Cardiovasc Surg 2009; 137(2): 425-8.
[http://dx.doi.org/10.1016/j.jtcvs.2008.05.046] [PMID: 19185164]
[http://dx.doi.org/10.1016/j.jtcvs.2008.05.046] [PMID: 19185164]
[21]
Torun S, Tunc BD, Suvak B, et al. Assessment of neutrophil-lymphocyte ratio in ulcerative colitis: a promising marker in predicting disease severity. Clin Res Hepatol Gastroenterol 2012; 36(5): 491-7.
[http://dx.doi.org/10.1016/j.clinre.2012.06.004] [PMID: 22841412]
[http://dx.doi.org/10.1016/j.clinre.2012.06.004] [PMID: 22841412]
[22]
Gao S-Q, Huang L-D, Dai R-J, Chen D-D, Hu W-J, Shan Y-F. Neutrophil-lymphocyte ratio: a controversial marker in predicting Crohn’s disease severity. Int J Clin Exp Pathol 2015; 8(11): 14779-85.
[PMID: 26823804]
[PMID: 26823804]
[23]
Omranzadeh A, Baradaran A, Ghodsi A, Arekhi S, Dadgarmoghaddam M, Mirshekaran A, et al. Neutrophil-to-lymphocyte ratio as an inflammatory marker in familial mediterranean fever: A systematic review and meta-analysis. J Child Sci 2021; 11(01): e100-9.
[24]
Goksugur SB, Kabakus N, Bekdas M, Demircioglu F. Neutrophil- to-lymphocyte ratio and red blood cell distribution width is a practical predictor for differentiation of febrile seizure types. Eur Rev Med Pharmacol Sci 2014; 18(22): 3380-5.
[PMID: 25491611]
[PMID: 25491611]
[26]
Aşkın A. Evaluation of neutrophil-lymphocyte ratio, platelet-lymphocyte ratio and mean platelet volume in patients with ankylosing spondylitis. Cukurova Med J 2016; 41(3): 479-84.
[27]
Özşahin M, Demirin H, Uçgun T, Ermiş F, Admış Ö, Ataoğlu S. Neutrophil-lymphocyte ratio in patients with ankylosing spondylitis. Abant Med J 2014; 3(1): 16-20.
[http://dx.doi.org/10.5505/abantmedj.2014.16878]
[http://dx.doi.org/10.5505/abantmedj.2014.16878]
[28]
Yang Z, Zhang Z, Lin F, et al. Comparisons of neutrophil-, monocyte-, eosinophil-, and basophil- lymphocyte ratios among various systemic autoimmune rheumatic diseases. APMIS 2017; 125(10): 863-71.
[http://dx.doi.org/10.1111/apm.12722] [PMID: 28766758]
[http://dx.doi.org/10.1111/apm.12722] [PMID: 28766758]
[29]
Zhu S, Cai M, Kong X, Yang F, Huang C, Wang Q. Changes of neutrophil-to-lymphocyte ratio and red blood cell distribution width in ankylosing spondylitis. Int J Clin Exp Pathol 2016; 9(8): 8570-4.
[30]
Boyraz I, Onur Caglar S, Erdem F, et al. Assessment of relation between neutrophil lympocyte, platelet lympocyte ratios and epicardial fat thickness in patients with ankylosing spondylitis. Med Glas 2016; 13(1): 14-7.
[PMID: 26827703]
[PMID: 26827703]
[31]
Zahorec R. Ratio of neutrophil to lymphocyte counts--rapid and simple parameter of systemic inflammation and stress in critically ill. Bratisl Lek Listy 2001; 102(1): 5-14.
[PMID: 11723675]
[PMID: 11723675]
[32]
Ghodsi A, Mirimoghaddam MM, Sarabi M, Dehghan Tarazjani A, Omranzadeh A, Mahdavi Rashed M, et al. Neutrophil-to-lymphocyte ratio as a novel and valuable marker for assessing disease severity in Ulcerative colitis, Multiple sclerosis, and Kawasaki disease: A review. J Basic Res Med Sci 2020; 7(3): 62-70.
[33]
Babaniamansour P, Mohammadi M, Babaniamansour S, Aliniagerdroudbari E. The relation between atherosclerosis plaque composition and plaque rupture. J Med Signals Sens 2020; 10(4): 267-73.
[PMID: 33575199]
[PMID: 33575199]
[34]
Kusumanto YH, Dam WA, Hospers GA, Meijer C, Mulder NH. Platelets and granulocytes, in particular the neutrophils, form important compartments for circulating vascular endothelial growth factor. Angiogenesis 2003; 6(4): 283-7.
[http://dx.doi.org/10.1023/B:AGEN.0000029415.62384.ba] [PMID: 15166496]
[http://dx.doi.org/10.1023/B:AGEN.0000029415.62384.ba] [PMID: 15166496]
[35]
Scapini P, Calzetti F, Cassatella MA. On the detection of neutrophil-derived vascular endothelial growth factor (VEGF). J Immunol Methods 1999; 232(1-2): 121-9.
[http://dx.doi.org/10.1016/S0022-1759(99)00170-2] [PMID: 10618514]
[http://dx.doi.org/10.1016/S0022-1759(99)00170-2] [PMID: 10618514]
[36]
Niu X-Y, Zhang H-Y, Liu Y-J, Zhao D, Shan Y-X, Jiang Y-F. Peripheral B-cell activation and exhaustion markers in patients with ankylosing spondylitis. Life Sci 2013; 93(18-19): 687-92.
[http://dx.doi.org/10.1016/j.lfs.2013.09.003] [PMID: 24044883]
[http://dx.doi.org/10.1016/j.lfs.2013.09.003] [PMID: 24044883]
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