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

Young Ho Lee; Gwan Gyu Song

doi:10.4078/jrd.2017.24.5.279

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

Original Article

J Rheum Dis 2017;24(5):279-286.

Published online: 31 October 2017

DOI: https://doi.org/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

Young Ho Lee, Gwan Gyu Song

Division of Rheumatology, Department of Internal Medicine, Korea University Medical Center, Korea University College of Medicine, Seoul, Korea

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

Received 2 June 201730 June 2017 Accepted 30 June 2017

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

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.

Keywords: Blood cell count, Systemic lupus erythematosus

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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.

Table 1.

Characteristics of the individual studies included in the meta-analysis

Study	Country	Group	Number		Data	Matched	Result			Study quality
Study	Country	Group	Case	Control	Data	Matched	SMD	Magnitude^*	p-value	Study quality
Yolbas, 2016 [3]	Turkey	NLR	51	55	Calculated	NA	1.330	Large	<0.001	6
Wu, 2016 [10]	China	NLR	116	136	Calculated	Age, sex	3.698	Large	<0.001	7
Qin, 2016 [11]	China	NLR	154	151	Original	Age, sex	5.174	Large	<0.001	8
Li-1, 2015 [12]	China	NLR	20	149	Original	Age, sex	2.424	Large	<0.001	8
Li-2, 2015 [12]	China	NLR	59	149	Original	Age, sex	1.127	Large	<0.001	8
Khan, 2017 [17]	Pakistan	MPV	50	NA	Original	Age, sex	NA	NA	NA	7
Yolbas, 2016 [3]	Turkey	MPV	51	55	Original	NA	0.438	Small	0.026	7
Qin, 2016 [11]	China	MPV	154	151	Original	Age, sex	0.460	Small	<0.001	8
El-Garf, 2016 [16]	Egypt	MPV	29	36	Original	Age, sex	1.675	Large	<0.001	8
Safak, 2014 [13]	Turkey	MPV	44	44	Original	Age, sex	−0.954	Large	<0.001	8
Yavuz, 2014 [14]	Turkey	MPV	20	30	Original	Age, sex	1.449	Large	<0.001	8
Yolbas, 2016 [3]	Turkey	PLR	51	55	Calculated	NA	1.530	Large	<0.001	6
Wu, 2016 [10]	China	PLR	116	136	Calculated	Age, sex	2.712	Large	<0.001	7
Qin, 2016 [11]	China	PLR	154	151	Original	Age, sex	0.461	Small	<0.001	8
Ayna, 2017 [15]	Turkey	NLR	78	30	Original	NA	83^†	54^‡	NA	7
Qin, 2016 [11]	China	NLR	99	55	Original	NA	70.7^†	63.6^‡	NA	7
Li, 2015 [12]	China	NLR	20	59	Original	NA	64.7^†	91.6^‡	NA	7

SMD: standardized mean difference, NLR: neutrophil to lymphocyte ratio, MPV: mean platelet volume, PLR: platelet to lymphocyte ratio, 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.

^† Sensitivity for diagnosis of lupus nephritis

^‡ specificity for diagnosis of lupus nephritis.

Table 2.

Meta-analysis of the association between NLR, PLR, and MPV and SLE

Group	Population	No. of studies	Test of association			Test of heterogeneity
Group	Population	No. of studies	SMD	95% CI	p-value	Model	p-value	I²
NLR	Overall	5	2.747	1.241∼4.254	<0.001	R	<0.001	98.4
PLR	Overall	3	1.564	0.122∼3.006	<0.001	R	<0.001	98.2
MPV	Overall	5	0.590	−0.157∼1.337	0.121	R	<0.001	93.9

NLR: neutrophil to lymphocyte ratio, PLR: platelet to lymphocyte ratio, MPV: mean platelet volume, SLE: systemic lupus erythematosus, SMD: standard mean difference, CI: confidence interval, R: random effects model.

Table 3.

Meta-analysis of the correlation coefficients between NLR, PLR, and MPV and SLE activity (SLEDAI) (A) and of the diagnostic accuracy of NLR for lupus nephrtitis (B)

A.
Group	Population	No. of studies	Test of association			Test of heterogeneity
Group	Population	No. of studies	Correlation coefficient	95% CI	p-value	Model	p-value	I²
NLR	Overall	2	0.404	0.299∼0.500	<0.001	R	0.128	56.2
PLR	Overall	2	0.378	0.234∼0.505	<0.001	R	0.191	41.5
MPV	Overall	2	−0.665	−0.965∼0.382	0.192	R	<0.001	98.0
NLR: neutrophil to lymphocyte ratio, PLR: platelet to lymphocyte ratio, MPV: mean platelet volume, SLEDAI: systemic lupus erythematosus disease activity index, CI: confidence interval, R: random effects model.

B.
Population	No. of studies	Sensitivity (95% CI)	Specificity (95% CI)	PLR (95% CI)	NLR (95% CI)	AUC (SE)	Q^*(SE)
Overall	3	0.751 (0.685∼0.810)	0.729 (0.649∼0.800)	2.575 (1.403∼4.726)	0.407 (0.309∼0.537)	0.794 (0.046)	0.731 (0.039)

^* CI: confidence interval, PLR: positive likelihood ratio, NLR: negative likelihood ratio, AUC: area under the curve, SE: standard error.

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