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

Young Ho Lee

doi:10.4078/jrd.2018.25.3.169

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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

Original Article

J Rheum Dis 2018;25(3):169-178.

Published online: 31 July 2018

DOI: https://doi.org/10.4078/jrd.2018.25.3.169

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

Young Ho Lee

Division of Rheumatology, Department of Internal Medicine, Anam Hospital, Korea University College of Medicine, Seoul, Korea

Corresponding to: Young Ho Lee, http://orcid.org/0000-0003-4213-1909 Division of Rheumatology, Department of Internal Medicine, Anam Hospital, Korea University College of Medicine, 73 Inchon-ro, Seongbuk-gu, Seoul 02841, Korea. E-mail: lyhcgh@korea.ac.kr

Received 12 October 201711 March 2018 Accepted 14 March 2018

This is a Open Access article, which permits unrestricted non-commerical use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.

Keywords: Neutrophil-to-lymphocyte ratio, Platelet-to-lymphocyte ratio, Mean platelet volume, Rheumatoid arthritis

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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.

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.

Figure 1.

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

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.

Table 1.

Characteristics of the individual studies included in the meta-analysis

Test	Author	Country	Number		Matched	DAS28	Result
Test	Author	Country	Case	Control	Matched	DAS28	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
Group	Population	Study (n)	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
Test	Population	Study (n)	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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