YKL-40 Levels in Rheumatoid Arthritis and Their Correlation with Disease Activity: A Meta-analysis

Young Ho Lee; Gwan Gyu Song

doi:10.4078/jrd.2019.26.4.257

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Lee and Song: YKL-40 Levels in Rheumatoid Arthritis and Their Correlation with Disease Activity: A Meta-analysis

Original Article

J Rheum Dis 2019;26(4):257-263.

Published online: 31 October 2019

DOI: https://doi.org/10.4078/jrd.2019.26.4.257

YKL-40 Levels in Rheumatoid Arthritis and Their Correlation with Disease Activity: A Meta-analysis

Young Ho Lee, Gwan Gyu Song

Department of Rheumatology, 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, Korea University Anam Hospital, Korea University College of Medicine, 73 Inchon-ro, Seongbuk-gu, Seoul 02841, Korea. E-mail: lyhcgh@korea.ac.kr

Received 23 May 201922 June 2019 Accepted 22 July 2019

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

To examine the relationship of serum/plasma YKL-40 levels with rheumatoid arthritis (RA) and their correlation with RA activity and rheumatoid factor (RF) level.

Methods

We performed a meta-analysis comparing the serum/plasma YKL-40 levels between patients with RA and controls and examined the correlation coefficients of the circulating YKL-40 level with the RF level and RA activity based on the 28-joint disease activity score (DAS28), erythrocyte sedimentation rate (ESR), and C-re-active protein (CRP) level.

Results

Nine studies (707 patients with RA and 1,041 controls) were included in the meta-analysis. The YKL-40 levels were significantly higher in the RA group than in the control group (standardized mean difference [SMD]=1.071, 95% confidence interval [CI]=0.726∼1.417, p<0.001). Stratification by ethnicity showed significantly elevated YKL-40 levels in the RA groups from European, Asian, North American, and Arab populations. The YKL-40 level was significantly higher in the RA group than in the control group in both age- and sex-matched and only age-matched populations (SMD=0.937, 95% CI=0.554∼1.320, p<0.001; SMD=2.951, 95% CI=1.389∼4.512, p<0.001, respectively). Subgroup analysis by sample size showed significantly increased YKL-40 levels in the RA group in both small (n<100) and large (n>100) populations. Meta-analysis of correlation coefficients showed a significant positive correlation between the YKL-40 levels and DAS28, ESR, CRP level, and RF level (DAS28: correlation coefficient=0.381, 95% CI=0.044∼0.640, p=0.028; RF level: correlation coefficient=0.341, 95% CI=0.176∼0.487, p<0.001).

Conclusion

The circulating YKL-40 levels are high in patients with RA and positively correlate with RA activity and RF level.

Keywords: YKL-40, Rheumatoid arthritis, Activity

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Figure 1.

Meta-analysis of the relationship between the plasma/serum YKL-40 levels and rheumatoid arthritis (RA) in all study subjects. Std diff: standardized difference, CI: confidence interval.

Figure 2.

Meta-analysis of the relationship between the plasma/serum YKL-40 levels and rheumatoid arthritis (RA) in each ethnic group. Std diff: standardized difference, CI: confidence interval.

Figure 3.

Meta-analysis of the correlation coefficient between the YKL-40 levels and DAS28 (A) and ESR (B). DAS28: 28-joint disease activity score, ESR: erythrocyte sedimentation rate, CI: confidence interval.

Table 1.

Characteristics of individual studies included in the meta-analysis

Authors	Country	Ethnicity	Number of patients		YKL-40 level (mean)		YKL-40, unit	Matched for age and/or sex	Data type
Authors	Country	Ethnicity	RA	Control	RA	Control	YKL-40, unit	Matched for age and/or sex	Data type
Jafari-Nakhjavani et al., 2019 [12]	Iran	Arab	60	30	951.63	444.92	pg/mL	Age, sex	Original
Basok et al., 2014 [13]	Turkey	European	27	27	66.95	48.70	ng/mL	Age, sex	Original
Turkyilmaz et al., 2013 [6]	Turkey	European	42	35	124.30	67.20	ng/mL	Age, sex	Original
Kozakova et al., 2013 [7]	Bulgaria	European	25	40	246.17	84.19	ng/mL	Age, sex	Original
Nielsen et al., 2011 [8]	Denmark	European	308	605	86.00	46.00	ng/mL	Age	Original
Janckila et al., 2008 [10]	USA	North American	50	26	710.00	67.15	μ g/L	Sex	Original
Matsumoto et al.-1, 2001 [14]	Japan	Asian	56	26	197.00	68.75	pg/mL	Age, sex	Calculated^*
Matsumoto et al.-2, 2001 [14]	Japan	Asian	16	14	220.00	77.25	pg/mL	Age, sex	Calculated^*
Johansen et al., 2001 [9]	USA	North American	76	191	156.25	72.00	ug/L	Age	Calculated^*
Vos et al., 2000 [11]	Netherlands European		47	47	38.30	15.50	ng/mL	Age, sex	Original

RA: rheumatoid arthritis, USA: United States of America.

^* The means±standard deviations were calculated from the medians and ranges.

Table 2.

Meta-analysis of the YKL-40 levels between the patients with RA and controls

Groups	Population	Number of studies	Test of association			Test of heterogeneity
Groups	Population	Number of studies	SMD^*	95% CI	p-value	Model	p-value	I²
All	Overall	10	1.071	0.726∼1.417	<0.001	R	<0.001	86.6
Ethnicity	European	5	0.762	0.418∼1.127	<0.001	R	<0.001	74.8
	Asian	2	1.353	0.921∼1.785	<0.001	F	0.173	55.8
	North American	2	1.552	0.565∼2.539	0.002	R	0.001	90.9
	Arab	1	0.954	0.494∼1.414	<0.001	NA	NA	NA
Matched for age and/or sex	Both	7	0.937	0.554∼1.320	<0.001	R	0.001	73.8
	Age or sex	3	2.951	1.389∼4.512	<0.001	R	<0.001	98.4
Sample size	n<100	8	0.943	0.610∼1.276	<0.001	R	<0.001	70.2
	n>100	2	1.463	0.358∼2.568	0.029	R	<0.001	97.5
Data type	Original	7	0.824	0.572∼1.075	<0.001	R	0.011	63.7
	Calculated	3	1.703	1.081∼2.325	<0.001	R	<0.001	76.5

RA: rheumatoid arthritis, SMD: standardized mean difference, CI: confidence interval, F: fixed effects model, R: random effects model, NA: not applicable.

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

Table 3.

Meta-analysis of the correlation coefficient between the YKL-40 level and RA activity (DAS28, ESR, and CRP level) and RF level

Comparison	Number of studies	Test of association			Test of heterogeneity
Comparison	Number of studies	Correlation coefficient	95% CI	p-value	Model	l p-value	I²
DAS28	4	0.381	0.044∼0.640	0.028	R	0.001	80.6
ESR	3	0.402	0.216∼0.560	<0.001	F	0.981	0
CRP level	2	0.531	0.269∼0.693	<0.001	F	0.513	0
RF level	3	0.341	0.176∼0.487	<0.001	F	0.113	54.1

RA: rheumatoid arthritis, DAS28: 28-joint disease activity score, ESR: erythrocyte sedimentation rate, CRP: C-reactive protein, RF: rheumatoid factor, CI: confidence interval, R: random effects model, F: fixed effects model.

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