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Journal of Peking University (Health Sciences) ›› 2024, Vol. 56 ›› Issue (6): 956-962. doi: 10.19723/j.issn.1671-167X.2024.06.003

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Diagnostic significance of serum chemokine CXCL-10 and Krebs von den lungen-6 level in patients with rheumatoid arthritis associated interstitial lung disease

Rui YAN1, Dan KE1, Yan ZHANG1, Li LI1, Huanran SU1, Wei CHEN2, Mingxia SUN2, Xiaomin LIU1,*(), Liang LUO3,*()   

  1. 1. Department of Rheumatology and Immunology, Beijing Shunyi Hospital, Beijing 101300, China
    2. Department of Radiology, Beijing Shunyi Hospital, Beijing 101300, China
    3. Department of Chinese Medicine, the People' s Hospital of Yubei District of Chongqing, Chongqing 401120, China
  • Received:2024-07-09 Online:2024-12-18 Published:2024-12-18
  • Contact: Xiaomin LIU, Liang LUO E-mail:lxm101300@yahoo.com.cn;luoliang202112@163.com
  • Supported by:
    Chongqing Science and Health Joint Traditional Chinese Medicine Research Project(2024ZYQN002)

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Abstract:

Objective: To detect the serum level of chemokine CXC motif chemokine 10 (CXCL-10) and Krebs von den lungen-6 (KL-6) in patients with rheumatoid arthritis associated interstitial lung disease (RA-ILD), and to analyze their correlation with RA-ILD, as well as the significance in RA-ILD. Methods: A total of 169 RA patients were enrolled in the study. According to imaging findings of with and without ILD in high-resolution computed tomography scans of chest, the subjects were divided into RA-ILD group and RA-non-ILD group. According to the inclusion and exclusion criteria, 80 patients in each of the two groups were finally selected. Two groups were matched according to the 1 ∶ 1 ratio using propensity score matching (PSM). The serum CXCL-10 and KL-6 levels were detected by enzyme-linked immunosorbent assay. The clinical features, laboratory data and medications between the two groups were compared after PSM and the correlation between serum levels and clinical parameters were analyzed. Binary Logistic regression was used to analyze the risk factors of ILD in the RA patients, and the predictive value of CXCL-10 and KL-6 in RA-ILD was evaluated. Results: In this study, 49 patients with RA-ILD and 49 patients with RA-non-ILD were selected by PSM. The levels of CXCL-10 and KL-6 in the RA-ILD group [64.36 (34.01, 110.18) ng/L, 360.70 (236.35, 715.05) U/mL] were significantly higher than those in the RA-non-ILD group [29.80 (16.89, 40.55) ng/L, 210.69 (159.98, 255.50) U/mL] (all P < 0.001). The results of correlation analysis showed that the level of serum CXCL-10 was positively correlated with the Warrick score on chest CT (r=0.378, P=0.007) and negatively correlated with the percentage of forced vital capacity to the predicted value (FVC%, r=-0.338, P=0.018). And the level of KL-6 was positively correlated with rheumatoid factor (RF, r=0.296, P=0.039) and negatively correlated with FVC% (r=-0.436, P=0.002) and the percentage of diffusion capacity for carbon monoxide to the predicted value (DLCO%, r=-0.426, P=0.002). Both univariate and multivariate Logistic regression analysis showed that CXCL-10 and KL-6 were positively correlated with ILD, the values of OR were 1.035 and 1.023 in CXCL-10 and those were 1.004 and 1.005 in KL-6 respectively (P < 0.05). The ROC curves were plotted with CXCL-10 and KL-6. The area under the curve (AUC) was 0.770 and 0.752 respectively. The AUC of combined detection increased to 0.800. Conclusion: Serum levels of CXCL-10 and KL-6 are significantly elevated in patients with RA-ILD and correlated with the severity of ILD. The combined estimate of them helps to improve the effectiveness of diagnosis.

Key words: Chemokine, CXC motif chemokine 10(CXCL-10), Rheumatoid arthritis, Interstitial lung disease

CLC Number: 

  • R593.22

Figure 1

Consort flowchart of the study RA-ILD, rheumatoid arthritis associated interstitial lung disease; RA-non-ILD, rheumatoid arthritis without interstitial lung disease."

Table 1

Comparison between the two groups of RA-non-ILD and RA-ILD before and after PSM"

ItemsBefore PSM After PSM
RA-non-ILD (n=80) RA-ILD (n=80) P RA-non-ILD (n=49) RA-ILD (n=49) P
Age/years 59.5 (51.0, 65.0) 67.0 (62.0, 71.0) ＜0.001 62.0 (57.0, 65.5) 67.0 (57.0, 67.0) 0.654
Disease duration/years 6 (3, 13) 10 (5, 15) 0.004 10 (3, 15) 10 (5, 14) 0.754
Gender (Male) 15 (18.8) 35 (43.8) 0.001 12 (24.5) 11 (22.4) 0.812
History of smoking 6 (7.5) 14 (17.5) 0.056 5 (10.2) 8 (16.3) 0.372
SJC 0 (0, 2) 1 (0, 4) 0.033 0 (0, 2) 1 (0, 3) 0.484
TJC 1 (0, 4) 1 (0, 5) 0.439 1 (0, 4) 1 (0, 4) 0.708

Table 2

Comparison of disease activity, serological tests and treatment status between two groups after PSM"

Items RA-non-ILD (n=49) RA-ILD (n=49) Z/F/χ2 P
ESR/(mm/h) 27.00 (16.00, 45.50) 40.00 (30.00, 54.50) -3.152 0.002
CRP(mg/L) 0.41 (0.22, 0.87) 1.25 (0.83, 2.34) -4.747 ＜0.001
VAS/mm 10 (0, 20) 20 (0, 47.5) -2.163 0.031
DAS28-ESR 3.38 (2.41, 4.05) 3.56 (2.85, 4.68) -1.922 0.055
RF/(IU/mL) 55.50 (22.45, 332.00) 105.0 (50.40, 361.50) -1.483 0.138
MCV/(U/mL) 321.00 (103.00, 741.50) 437.0 (195.00, 730.00) -0.821 0.412
CCP/(U/mL) 150.00 (36.90, 201.00) 201.00 (99.60, 201.00) -1.819 0.069
KL-6/(U/mL) 210.69 (159.98, 255.50) 360.70 (236.35, 715.05) -4.295 ＜0.001
CXCL-10/(ng/L) 29.80 (16.89, 40.55) 64.36 (34.01, 110.18) -4.611 ＜0.001
Corticosteroids in combination 8 (16.3) 17 (34.7) 4.352 0.037
Biologic agents in combination 12 (24.5) 20 (40.8) 2.970 0.085
FVC% 86.00 (80.80, 90.80) 70.00 (64.20, 78.20) -7.581 ＜0.001
DLCO% 81.00 (76.00, 88.50) 70.00 (61.00, 76.20) -5.955 ＜0.001

Table 3

Correlation between serum CXCLl0 and KL-6 levels with clinical characteristics and laboratory parameters in RA-ILD patients"

ItemsCXCL-10 KL-6
r P r P
Age -0.240 0.097 0.069 0.637
Disease duration 0.134 0.358 0.115 0.432
VAS 0.059 0.688 -0.130 0.373
SJC 0.210 0.148 0.043 0.768
TJC 0.195 0.180 -0.079 0.592
ESR -0.190 0.190 0.021 0.888
CRP -0.158 0.278 0.040 0.785
DAS28-ESR 0.096 0.512 -0.105 0.473
Warrick 0.378 0.007 0.103 0.482
RF 0.084 0.568 0.296 0.039
CCP 0.080 0.585 -0.019 0.895
FVC% -0.338 0.018 -0.436 0.002
DLCO% -0.268 0.063 -0.426 0.002

Table 4

Binary Logistic regression analysis results of risk factors related to RA-ILD, rheumatoid arthritis associated interstitial lung disease"

ParametersUnivariate Multivariate
OR(95%CI) P OR(95%CI) P
DAS28-ESR 1.372 (0.982，1.917) 0.064 1.297 (0.875，1.922) 0.195
RF 1.000 (0.999，1.001) 0.493 1.000 (0.998，1.001) 0.472
CCP 1.005 (0.999，1.011) 0.084 1.004 (0.997，1.011) 0.228
KL-6 1.004 (1.002，1.006) ＜0.001 1.005 (1.001，1.008) 0.005
CXCL-10 1.035 (1.018，1.052) ＜0.001 1.023 (1.005，1.042) 0.013

Figure 2

Clinical value of CXCL-10 and KL-6 in the diagnosis of RA-ILD CXCL-10, CXC motif chemokine 10; AUC, area under the curve; KL-6, Krebs von den lungen-6; RA, rheumatoid arthritis; ILD, interstitial lung disease."

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