Journal List > J Rheum Dis > v.25(3) > 1099060

Lee: Association between the Neutrophil-to-lymphocyte Ratio, and Platelet-to-lymphocyte Ratio and Rheumatoid Arthritis and their Correlations with the Disease Activity: A Meta-analysis

Abstract

Objective

This study examined the relationship between neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), mean platelet volume (MPV), and rheumatoid arthritis (RA), to establish a correlation among the NLR, PLR, and MPV and RA activity.

Methods

Medline, Embase, and Cochrane were searched, and a meta-analysis was performed to compare the NLR, PLR, and MPV between RA patients and healthy controls. The correlation coefficients between NLR, PLR, and MPV and the Disease Activity Score 28 (DAS28) in the RA patients were examined.

Results

Sixteen studies were included in this meta-analysis. NLR was significantly higher in the RA group (standardized mean difference [SMD], 0.800; 95% confidence interval [CI], 0.542∼1.058; p<0.001). Stratification according to ethnicity revealed a significantly elevated NLR in the RA group in Asian and Turkish populations (SMD, 95% CI: 0.994, 0.418∼1.519, p=0.001 and 0.695, 0.443∼0.948, p<0.001, respectively). Subgroup analysis revealed a significantly high NLR in RA, independent of the data type and adjustment for age and/or sex. PLR was also significantly higher in the RA group (SMD, 0.708; 95% CI, 0.401∼0.995; p<0.001), regardless of ethnicity, data type, and adjustment for age and/or sex. In addition, NLR and PLR were positively associated with the RA activity based on the DAS28 (correlation coefficient, 95% CI: 0.277, 0.190∼0.359, p<0.001 and 0.318, 0.197∼0.430, p<0.001, respectively). However, MPV showed no correlation with the RA activity (correlation coefficient, −0.095; 95% CI, −0.435 to 0.269; p=0.615).

Conclusion

Meta-analysis showed that the NLR and PLR were significantly higher in the RA patients and positively but weakly correlated with the RA activity.

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Supplementary Figure 1.
Sensitivity analysis. NLR: neutrophil-to-lymphocyte ratio, PLR: platelet-to-lymphocyte ratio, MPV: mean platelet volume, Std diff: standard difference, CI: confidence interval, RA: rheumatoid arthritis.
jrd-25-169f3.tif
Supplementary Figure 2.
Funnel plot of publication bias. NLR: neutrophil-to-lymphocyte ratio, PLR: platelet-to-lymphocyte ratio, MPV: mean platelet volume, Std diff: standard difference, Std Err: standard error.
jrd-25-169f4.tif
Figure 1.
Flow diagram of the study selection process. SLE: systemic lupus erythematosus.
jrd-25-169f1.tif
Figure 2.
Meta-analysis of the relationship of (A) NLR, (B) PLR, and (C) MPV to RA and the correlation coefficients between (D) NLR, (E) PLR, and (F) MPV and DAS28. NLR: neutrophil-to-lymphocyte ratio, PLR: plate-let-to-lymphocyte ratio, MPV: mean platelet volume, RA: rheumatoid arthritis, DAS28: Disease Activity Score 28, Std diff: standard difference, CI: confidence interval.
jrd-25-169f2.tif
Table 1.
Characteristics of the individual studies included in the meta-analysis
Test Author Country Number Matched DAS28 Result
Case Control SMD* Magnitude* p-value
NLR Maden, 2017 [23] Turkey 82 61 NA NA 0.888 Large <0.001
  Zhang-1, 2016 [24] China 125 126 Age, sex NA 0.831 Large <0.001
  Zhang-2, 2016 [24] China 59 126 Age, sex NA 0.557 Medium 0.001
  Gökmen, 2016 [25] Turkey 84 60 Age, sex NA 0.661 Medium <0.001
  Yolbas, 2016 [7] Turkey 91 55 NA NA 1.219 Large <0.001
  Tekeoğ lu, 2016 [14] Turkey 102 NA NA 0.193 NA NA NA
  Zengin, 2016 [15] Turkey 205 104 NA NA 0.505 Medium <0.001
  Mercan, 2016 [8] Turkey 136 117 NA 0.310 0.300 Small 0.018
  Uslu, 2015 [16] Turkey 104 51 Age, sex 0.345 0.715 Medium <0.001
  Fu, 2015 [17] China 128 78 Age, sex 0.250 1.601 Large <0.001
PLR Zhang-1, 2016 [24] China 125 126 Age, sex NA 0.806 Large <0.001
  Zhang-2, 2016 [24] China 59 126 Age, sex NA 0.711 Medium <0.001
  Yolbas, 2016 [7] Turkey 91 55 NA NA 1.248 Large <0.001
  Zengin, 2016 [15] Turkey 205 104 NA NA 0.338 Small 0.005
  Mercan, 2016 [8] Turkey 136 117 NA NA 0.264 Small 0.037
  Uslu, 2015 [16] Turkey 104 51 Age, sex 0.352 0.461 Small 0.008
  Fu, 2015 [17] China 128 78 Age, sex 0.290 1.199 Large <0.001
MPV Maden, 2017 [23] Turkey 82 61 NA NA 1.454 Large <0.001
  Talukdar-1, 2017 [19] India 48 80 Age, sex NA 0.614 Medium 0.001
  Talukdar-2, 2017 [19] India 32 80 Age, sex NA 1.861 Large <0.001
  Gokmen, 2016 [25] Turkey 84 60 Age, sex NA 0.384 Small 0.024
  Yolbas, 2016 [7] Turkey 91 55 NA NA 0.064 No effect 0.708
  Tekeoğ lu, 2016 [14] Turkey 102 NA NA 0.316 NA NA NA
  Tecer, 2016 [18] Turkey 100 100 Age, sex NA 0.951 Large <0.001
  Cakir, 2016 [26] Turkey 81 80 Age, sex NA 0.749 Medium <0.001
  Yildirim, 2015 [27] Turkey 90 52 Age, sex 0.231 0.506 Medium 0.004
  Yazici, 2010 [20] Turkey 97 33 Age, sex 0.270 0.615 Medium 0.003
  Gasparyan, 2010 [22] UK 400 360 NA NA 0.231 Small 0.002
  Kisacik, 2008 [21] Turkey 32 29 Age NA 1.660 Large <0.001

DAS28: Disease Activity Score 28, SMD: standardized mean difference, NLR: neutrophil-to-lymphocyte ratio, PLR: platelet-to-lymphocyte ratio, MPV: mean platelet volume, NA: not available.

* Magnitude of Cohen's d effect size: 0.2∼0.5, small effect; 0.5∼0.8, medium effect; ≥0.8, large effect.

Table 2.
Meta-analysis of the association of NLR, PLR, and MPV with RA
Group Population Study (n) Test of association Test of heterogeneity
SMD* 95% CI p-value Model p-value I2
NLR                
  Overall 9 0.800 0.542∼1.058 <0.001 R <0.001 84.8
Ethnicity Asian 3 0.994 0.418∼1.519 0.001 R <0.001 91.1
  Turkish 6 0.695 0.443∼0.948 <0.001 R 0.001 75.4
Data type Original 5 0.588 0.389∼0.787 <0.001 R 0.063 55.2
  Calculated 4 1.047 0.607∼1.488 <0.001 R <0.001 87.5
Age/sex-matche ed Yes 5 0.874 0.517∼1.230 <0.001 R <0.001 84.6
  No 4 0.709 0.331∼1.086 <0.001 R <0.001 84.9
PLR                
  Overall 7 0.708 0.401∼0.995 <0.001 R <0.001 85.5
Ethnicity Asian 3 0.904 0.622∼1.185 <0.001 R 0.062 64.0
  Turkish 4 0.560 0.173∼0.947 0.005 R <0.001 85.9
Data type Original 3 0.335 0.182∼0.488 <0.001 F 0.656 0
  Calculated 4 0.980 0.720∼1.239 <0.001 R 0.037 64.7
Age/sex-matched Yes 4 0.800 0.514∼1.087 <0.001 R 0.013 72.0
  No 3 0.599 0.075∼1.122 0.025 R <0.001 90.6
MPV                
  Overall 11 0.049 0.425∼0.524 0.838 R <0.001 95.9
Data type Original 9 0.116 0.525∼0.757 0.723 R <0.001 96.2
  Calculated 2 0.248 1.208∼0.712 0.613 R <0.001 96.6
Age/sex-matched Yes 8 0.227 0.414∼0.868 0.487 R <0.001 95.8
  No 3 0.418 1.356∼0.520 0.382 R <0.001 97.1

NLR: neutrophil-to-lymphocyte ratio, PLR: platelet-to-lymphocyte ratio, MPV: mean platelet volume, RA: rheumatoid arthritis, SMD: standard mean difference, CI: confidence interval, R: random-effects model, F: fixed effects model.

* Magnitude of Cohen's d effect size: 0.2∼0.5, small effect; 0.5∼0.8, medium effect; ≥0.8, large effect.

Table 3.
Meta-analysis of the correlation coefficients between NLR, PLR, and MPV and RA activity (DAS28)
Test Population Study (n) Test of association Test of heterogeneity
Correlation coefficient 95% CI p-value Model p-value I2
NLR Overall 4 0.277 0.190∼0.359 <0.001 F 0.651 0
  Asian 1 0.250 0.080∼0.406 0.004 NA NA NA
  Turkish 3 0.287 0.186∼0.382 <0.001 F 0.474 0
PLR Overall 2 0.318 0.197∼0.430 <0.001 F 0.605 0
  Asian Turkish 1 1 0.290 0.352 0.123∼0.441 0.171∼0.510 0.001 <0.001 NA NA NA NA NA NA
MPV Overall 3 0.095 0.435∼0.269 0.615 R <0.001 90.0

NLR: neutrophil-to-lymphocyte ratio, PLR: platelet-to-lymphocyte ratio, MPV: mean platelet volume, RA: rheumatoid arthritis, DAS28: Disease Activity Score 28, CI: confidence interval, F: fixed-effects model, R: random-effects model, NA: not available.

Table 4.
GRADE assessment of the meta-analysis results
Test Study (n) Study design Risk of bias Inconsistency Indirectness Imprecision Publication bias Quality
NLR 9 Case-control No No No No Undetected Low
PLR 7 Case-control No No No No Undetected Low
MPV 11 Case-control No Serious Serious Serious Undetected Very low
NLR (correlation) 4 Case-control No No No No Undetected Low
PLR (correlation) 2 Case-control No No No No Undetected Low
MPV (correlation) 3 Case-control No Serious Serious Serious Undetected Very low

GRADE: Grading of Recommendations Assessment, Development and Evaluation, NLR: neutrophil-to-lymphocyte ratio, PLR: platelet-to-lymphocyte ratio, MPV: mean platelet volume.

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