J Rheum Dis.  2017 Oct;24(5):279-286. 10.4078/jrd.2017.24.5.279.

Association of Neutrophil to Lymphocyte Ratio, Platelet to Lymphocyte Ratio, and Mean Platelet Volume with Systemic Lupus Erythematosus Disease Activity: A Meta-analysis

• Lee YH
• Song GG

• KMID: 2394343
• DOI: http://doi.org/10.4078/jrd.2017.24.5.279

Abstract

OBJECTIVE
A series of common blood tests neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and mean platelet volume (MPV) could provide a measure of systemic lupus erythematosus (SLE) activity.
METHODS
We searched the Medline, Embase, and Cochrane databases and performed a meta-analysis comparing NLR, PLR, and MPV in patients with SLE to controls, and examined correlation coefficients between NLR, PLR, and MPV and SLE activity based on SLE Disease Activity Index (SLEDAI) using random-effects models.
RESULTS
Nine studies were included in this meta-analysis. Meta-analysis revealed that NLR was significantly higher in the SLE group than in the control group (standard mean difference [SMD]=2.747, 95% confidence interval [CI]=1.241∼4.254, p<0.001). PLR was also significantly higher in the SLE group (SMD=1.564, 95% CI=0.122∼3.006, p=0.034). Meta-analysis of correlation coefficients showed that both NLR and PLR were positively associated with SLEDAI (correlation coefficient=0.404, 95% CI=0.299∼0.500, p<0.001; correlation coefficient=0.378, 95% CI=0.234∼0.505, p<0.001). The pooled sensitivity and specificity of NLR for diagnosis of lupus nephritis were 75.1% (95% CI, 68.5∼81.0) and 72.9% (95% CI, 64.9∼80.0), respectively. The area under the curve of NLR were 0.794. However, meta-analysis indicated no elevated MPV in the SLE group and no correlation between MPV and SLE activity.
CONCLUSION
This meta-analysis demonstrated that both NLR and PLR are higher in patients with SLE, a significantly positive correlation exists between NLR/PLR and SLE activity.

Keyword

Blood cell count; Systemic lupus erythematosus

MeSH Terms

Blood Cell Count
Blood Platelets*
Diagnosis
Hematologic Tests
Humans
Lupus Erythematosus, Systemic*
Lupus Nephritis
Lymphocytes*
Mean Platelet Volume*
Neutrophils*
Sensitivity and Specificity

Figure

• 

  Figure 1. Flow diagram of the study selection process. SLE: systemic lupus erythematosus.

• 

  Figure 2. Meta-analysis of the relationship between NLR (A), PLR (B), and MPV (C) and SLE compared with control. NLR: neutrophil to lymphocyte ratio, PLR: platelet to lymphocyte ratio, MPV: mean platelet volume, SMD: standard mean difference, CI: confidence interval, SLE: systemic lupus erythematosus.

• 

  Figure 3. Summary receiver-operating characteristic curves for neutrophil to lymphocyte ratio for the diagnosis of lupus nephritis. Solid circles represent individual studies included in this meta-analysis. The curve shown is a regression line that summarizes the overall diagnostic accuracy. SE (AUC): standard error of the area under the curve, Q*: an index defined by the point on the S receiver operating characteristics curve where the sensitivity and specificity are equal, and SE (Q*): Q* index standard error. SROC: summary receiver operating characteristic, AUC: area under the curve, SE: standard error.

Reference

1. Lisnevskaia L, Murphy G, Isenberg D. Systemic lupus erythematosus. Lancet. 2014; 384:1878–88.

2. Ohl K, Tenbrock K. Inflammatory cytokines in systemic lupus erythematosus. J Biomed Biotechnol. 2011; 2011; 432595.

3. Yolbas S, Yildirim A, Gozel N, Uz B, Koca SS. Hematological indices may be useful in the diagnosis of systemic lupus erythematosus and in determining disease activity in Behçet's disease. Med Princ Pract. 2016; 25:510–6.

4. Mercan R, Bitik B, Tufan A, Bozbulut UB, Atas N, Ozturk MA, et al. The association between neutrophil/lymphocyte ratio and disease activity in rheumatoid arthritis and ankylosing spondylitis. J Clin Lab Anal. 2016; 30:597–601.

5. Liu JF, Ba L, Lv H, Lv D, Du JT, Jing XM, et al. Association between neutrophil-to-lymphocyte ratio and differentiated thyroid cancer: a meta-analysis. Sci Rep. 2016; 6:38551.

6. Leader A, Pereg D, Lishner M. Are platelet volume indices of clinical use? A multidisciplinary review. Ann Med. 2012; 44:805–16.

7. Okyay GU, Inal S, Oneç K, Er RE, Paş aoğlu O, Paş aoğlu H, et al. Neutrophil to lymphocyte ratio in evaluation of inflammation in patients with chronic kidney disease. Ren Fail. 2013; 35:29–36.

8. Turkmen K, Erdur FM, Ozcicek F, Ozcicek A, Akbas EM, Ozbicer A, et al. Platelet-to-lymphocyte ratio better predicts inflammation than neutrophil-to-lymphocyte ratio in end-stage renal disease patients. Hemodial Int. 2013; 17:391–6.

9. Bath PM, Butterworth RJ. Platelet size: measurement, physiology and vascular disease. Blood Coagul Fibrinolysis. 1996; 7:157–61.

10. Wu Y, Chen Y, Yang X, Chen L, Yang Y. Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were associated with disease activity in patients with systemic lupus erythematosus. Int Immunopharmacol. 2016; 36:94–9.

11. Qin B, Ma N, Tang Q, Wei T, Yang M, Fu H, et al. Neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) were useful markers in assessment of inflammatory response and disease activity in SLE patients. Mod Rheumatol. 2016; 26:372–6.

12. Li L, Xia Y, Chen C, Cheng P, Peng C. Neutrophil-lympho-cyte ratio in systemic lupus erythematosus disease: a retrospective study. Int J Clin Exp Med. 2015; 8:11026–31.

13. Safak S, Uslu AU, Serdal K, Turker T, Soner S, Lutfi A. Association between mean platelet volume levels and inflammation in SLE patients presented with arthritis. Afr Health Sci. 2014; 14:919–24.

14. Yavuz S, Ece A. Mean platelet volume as an indicator of disease activity in juvenile SLE. Clin Rheumatol. 2014; 33:637–41.

15. Ayna AB, Ermurat S, Coşkun BN, Harman H, Pehlivan Y. Neutrophil to lymphocyte ratio and mean platelet volume as inflammatory indicators in systemic lupus erythematosus nephritis. Arch Rheumatol. 2017; 32:21–5.

16. El-Garf K, Marzouk H, Farag Y, Rasheed L, El-Garf A. Mean platelet volume is a marker of inflammation but not a marker of disease activity in children with juvenile SLE. Egypt Rheumatol. 2016; 38:35–9.

17. Khan A, Haider I, Ayub M, Khan S. Mean Platelet Volume (MPV) as an indicator of disease activity and severity in lupus. F1000Res. 2017; 6:126.

18. Lee YH, Woo JH, Choi SJ, Ji JD, Song GG. Induction and maintenance therapy for lupus nephritis: a systematic review and meta-analysis. Lupus. 2010; 19:703–10.

19. Lee YH, Woo JH, Choi SJ, Ji JD, Song GG. Association of programmed cell death 1 polymorphisms and systemic lupus erythematosus: a meta-analysis. Lupus. 2009; 18:9–15.

20. Lee YH, Woo JH, Choi SJ, Ji JD, Song GG. Associations between osteoprotegerin polymorphisms and bone mineral density: a meta-analysis. Mol Biol Rep. 2010; 37:227–34.

21. Moher D, Liberati A, Tetzlaff J, Altman DG. PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009; 6:e1000097.

22. Hozo SP, Djulbegovic B, Hozo I. Estimating the mean and variance from the median, range, and the size of a sample. BMC Med Res Methodol. 2005; 5:13.

23. Ridout KK, Ridout SJ, Price LH, Sen S, Tyrka AR. Depression and telomere length: a meta-analysis. J Affect Disord. 2016; 191:237–47.

24. Wells G, Shea B, O'Connell D, Peterson J, Welch V, Losos M, et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality if nonrandomized studies in meta-analyses [Internet]. Ottawa (ON): Ottawa Hospital Research Institute;2009. [cited 2009 Oct 19]. Available from:. http://www.ohri.ca/programs/clinical_epidemiology/oxford.htm.

25. Egger M, Smith GD, Phillips AN. Meta-analysis: principles and procedures. BMJ. 1997; 315:1533–7.

26. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986; 7:177–88.

27. Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002; 21:1539–58.

28. Walter SD. Properties of the summary receiver operating characteristic (SROC) curve for diagnostic test data. Stat Med. 2002; 21:1237–56.

29. Zamora J, Abraira V, Muriel A, Khan K, Coomarasamy A. Meta-DiSc: a software for meta-analysis of test accuracy data. BMC Med Res Methodol. 2006; 6:31.

30. Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997; 315:629–34.

31. Şahin A, Yetişgin A, Şahin M, Durmaz Y, Cengiz AK. Can mean platelet volume be a surrogate marker of inflammation in rheumatic diseases? West Indian Med J. 2015; 65:165–9.

32. Lipsky PE. Systemic lupus erythematosus: an autoimmune disease of B cell hyperactivity. Nat Immunol. 2001; 2:764–6.

33. Wong CK, Ho CY, Li EK, Lam CW. Elevation of proinflammatory cytokine (IL-18, IL-17, IL-12) and Th2 cytokine (IL-4) concentrations in patients with systemic lupus erythematosus. Lupus. 2000; 9:589–93.

34. Cassatella MA. The production of cytokines by polymorphonuclear neutrophils. Immunol Today. 1995; 16:21–6.

35. Boilard E, Blanco P, Nigrovic PA. Platelets: active players in the pathogenesis of arthritis and SLE. Nat Rev Rheumatol. 2012; 8:534–42.

36. Bashal F. Hematological disorders in patients with systemic lupus erythematosus. Open Rheumatol J. 2013; 7:87–95.

37. Talstad I, Scheie P, Dalen H, Röli J. Influence of plasma proteins on erythrocyte morphology and sedimentation. Scand J Haematol. 1983; 31:478–84.

38. Qin B, Ma N, Tang Q, Wei T, Yang M, Fu H, et al. Neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) were useful markers in assessment of inflammatory response and disease activity in SLE patients. Mod Rheumatol. 2016; 26:372–6.