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Journal of Peking University (Health Sciences) ›› 2021, Vol. 53 ›› Issue (6): 1026-1031. doi: 10.19723/j.issn.1671-167X.2021.06.003

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Effect of chemokines CXCL9 and CXCL10 on bone erosion in patients with rheumatoid arthritis

ZHONG Hua,XU Li-ling,BAI Ming-xin,SU Yin()   

  1. Beijing Key Laboratory for Rheumatism Mechanism and Immune Diagnosis, Beijing 100044, China
  • Received:2021-07-28 Online:2021-12-18 Published:2021-12-13
  • Contact: Yin SU E-mail:suyin0921@163.com
  • Supported by:
    National Natural Science Foundation of China(81671609);Beijing Scientific Program(Z191100006619111)

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Abstract:

Objective: To detect the serum level of soluble chemokines CXCL9 and CXCL10 in patients with rheumatoid arthritis (RA), and to analyze their correlation with bone erosion, as well as the clinical significance in RA. Methods: In the study, 105 cases of RA patients, 90 osteoarthritis (OA) patients and 25 healthy controls in Peking University People’s Hospital were included. All the clinical information of the patients was collected, and the serum CXCL9 and CXCL10 levels of both patients and healthy controls were measured by enzyme-linked immune sorbent assay (ELISA). CXCL9 and CXCL10 levels among different groups were compared. The correlation between serum levels with clinical/laboratory parameters and the occurrence of bone erosion in RA were analyzed. Independent sample t test, Chi square test, Mann-Whitney U test, Spearman’s rank correlation and Logistic regression were used for statistical analysis. Results: The levels of CXCL9 and CXCL10 were significantly higher in the RA patients [250.02 (126.98, 484.29) ng/L, 108.43 (55.16, 197.17) ng/L] than in the OA patients [165.05 (75.89, 266.37) ng/L, 69.00 (33.25, 104.74) ng/L] and the health controls [79.47 (38.22, 140.63) ng/L, 55.44 (18.76, 95.86) ng/L] (all P<0.01). Spearman’s correlation analysis showed that the level of serum CXCL9 was positively correlated with swollen joints (SJC), rheumatoid factor (RF) and disease activity score 28 (DAS28) (r=0.302, 0.285, 0.289; P=0.009, 0.015, 0.013). The level of serum CXCL10 was positively correlated with tender joints (TJC), SJC, C-reactive protein (CRP), immunoglobulin (Ig) A, IgM, RF, anti-cyclic citrullinated peptide antibody (ACPA), and DAS28 (r=0.339, 0.402, 0.269, 0.266, 0.345, 0.570, 0.540, 0.364; P=0.010, 0.002, 0.043, 0.045, 0.009, <0.001, <0.001, 0.006). Serum CXCL9 and CXCL10 levels in the RA patients with bone erosion were extremely higher than those without bone erosion [306.84 (234.02, 460.55) ng/L vs. 149.90 (75.88, 257.72) ng/L, 153.74 (89.50, 209.59) ng/L vs. 54.53 (26.30, 83.69) ng/L, respectively] (all P<0.01). Logistic regression analysis showed that disease duration, DAS28 and serum level of CXCL9 were correlated with bone erosion in the RA patients (P<0.05). Conclusion: Serum levels of CXCL9 and CXCL10 were remarkably elevated in patients with RA, and correlated with disease activities and occurrence of bone erosion. Chemokines CXCL9 and CXCL10 might be involved in the pathogenesis and bone destruction in RA.

Key words: Rheumatoid arthritis, Bone erosion, Chemokine CXCL9, Chemokine CXCL10

CLC Number: 

  • R593.22

Figure 1

Serum levels of CXCL9 and CXCL10 in RA patients compared with osteoarthritis and healthy control groups RA, rheumatoid arthritis; OA, osteoarthritis; HC, healthy controls."

Table 1

Correlation between serum CXCL9 and CXCL10 levels with clinical characteristics and laboratory parameters in RA patients"

Characteristics CXCL9 CXCL10
r P r P
SJC 0.302 0.009 0.402 0.002
TJC 0.160 0.176 0.339 0.010
ESR 0.145 0.222 0.201 0.135
CRP 0.076 0.523 0.269 0.043
IgA 0.161 0.175 0.266 0.045
IgG 0.067 0.571 0.192 0.153
IgM 0.229 0.051 0.345 0.009
RF 0.285 0.015 0.570 <0.001
ACPA 0.031 0.793 0.540 <0.001

Figure 2

Correlation between serum CXCL9 and CXCL10 levels with disease activities in RA patients DAS28, disease activity score 28; RA, rheumatoid arthritis."

Table 2

Clinical and biochemical characteristics of RA patients with or without bone erosion"

Items All subjects Without bone erosion With bone erosion P value
Patients, n 52 17 35
Gender, n
Female 38 12 26 0.778
Male 14 5 9
Age/years 56 (52, 66) 55 (51, 66) 57 (52, 70) 0.667
Disease duration/month 60 (21, 204) 36 (8, 66) 84 (24, 240) 0.010
SJC, n 4 (1, 8) 2 (0, 8) 5 (2, 8) 0.234
TJC, n 4 (1, 8) 5 (2, 8) 2 (1, 7) 0.169
ESR/(mm/h) 52 (24, 100) 33 (13, 88) 61 (36, 102) 0.077
CRP/(mg/L) 21.30 (6.42, 53.25) 11.40 (3.07, 48.95) 30.90 (9.10, 53.80) 0.084
IgA/(g/L) 2.43 (1.75, 3.59) 2.01 (1.69, 2.86) 2.59 (1.80, 3.81) 0.172
IgG/(g/L) 11.95 (10.43, 13.30) 10.70 (9.77, 12.80) 12.40 (10.70, 14.30) 0.141
IgM/(g/L) 1.29 (0.82, 1.78) 1.22 (0.73, 1.51) 1.34 (0.92, 1.93) 0.310
RF/(IU/mL) 136.50 (31.28, 340.25) 133.00 (34.15, 404.50) 138.00 (28.00, 353.00) 0.984
ACPA/(U/mL) 144.57 (23.91, 200.00) 118.02 (63.96, 200.00) 155.81 (8.36, 200.00) 0.579
DAS28 4.74±1.26 4.52±1.35 4.85±1.22 0.385
CXCL9/(ng/L) 280.27 (150.50, 439.83) 149.90 (75.88, 257.72) 306.84 (234.02, 460.55) <0.001
CXCL10/(ng/L) 107.10 (52.62, 200.33) 54.43 (26.30, 83.69) 153.74 (89.50, 209.59) 0.001

Table 3

Multiple Logistic regression analysis of factors associated with RA patients with bone erosion"

Items β Wald OR 95%CI P value
Disease duration 0.015 6.550 1.015 1.003-1.026 0.010
ACPA -0.005 0.834 0.995 0.985-1.006 0.361
DAS28 1.063 4.539 2.896 1.089-7.701 0.033
CXCL9 0.011 8.339 1.012 1.004-1.019 0.004
CXCL10 -0.004 3.204 0.996 0.992-1.000 0.073
[1] Sparks JA. Rheumatoid arthritis [J]. Ann Intern Med, 2019, 170(1): ITC1-ITC16.
doi: 10.7326/AITC201901010
[2] Zhu H, Li R, Da Z, et al. Remission assessment of rheumatoid arthritis in daily practice in China: A cross-sectional observational study[J]. Clin Rheumatol, 2018, 37(3):597-605.
doi: 10.1007/s10067-017-3850-z
[3] Zhou Y, Wang X, An Y, et al. Disability and health-related quality of life in Chinese patients with rheumatoid arthritis: A cross-sectional study[J]. Int J Rheum Dis, 2018, 21(9):1709-1715.
doi: 10.1111/apl.2018.21.issue-9
[4] Poeta VM, Massara M, Capucetti A, et al. Chemokines and chemokine receptors: new targets for cancer immunotherapy[J]. Front Immunol, 2019, 10:379.
doi: 10.3389/fimmu.2019.00379
[5] Susek KH, Karvouni M, Alici E, et al. The role of CXC chemokine receptors 1-4 on immune cells in the tumor microenvironment[J]. Front Immunol, 2018, 9:2159.
doi: 10.3389/fimmu.2018.02159
[6] Tokunaga R, Zhang W, Naseem M, et al. CXCL9, CXCL10, CXCL11/CXCR3 axis for immune activation: A target for novel cancer therapy[J]. Cancer Treat Rev, 2018, 63:40-47.
doi: S0305-7372(17)30199-8 pmid: 29207310
[7] McInnes IB, Schett G. The pathogenesis of rheumatoid arthritis[J]. N Engl J Med, 2011, 365(23):2205-2219.
doi: 10.1056/NEJMra1004965
[8] Muntyanu A, Abji F, Liang K, et al. Differential gene and protein expression of chemokines and cytokines in synovial fluid of patients with arthritis[J]. Arthritis Res Ther, 2016, 18(1):296.
doi: 10.1186/s13075-016-1196-6
[9] Antonelli A, Ferrari SM, Giuggioli D, et al. Chemokine (C-X-C motif) ligand CXCL10 in autoimmune diseases[J]. Autoimmun Rev, 2014, 13(3):272-280.
doi: 10.1016/j.autrev.2013.10.010
[10] Aletaha D, Neogi T, Silman AJ, et al. 2010 Rheumatoid arthritis classification criteria: An American College of Rheumatology/European League Against Rheumatism collaborative initiative[J]. Arthritis Rheum, 2010, 62(9):2569-2581.
doi: 10.1002/art.27584
[11] Zhang W, Doherty M, Peat G, et al. EULAR evidence-based recommendations for the diagnosis of knee osteoarthritis[J]. Ann Rheum Dis, 2010, 69(3):483-489.
doi: 10.1136/ard.2009.113100 pmid: 19762361
[12] Prevoo ML, van’t Hof MA, Kuper HH, et al. Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis[J]. Arthritis Rheum, 1995, 38(1):44-48.
doi: 10.1002/art.v38:1
[13] Fransen J, van Riel PL. The disease activity score and the EULAR response criteria [J]. Rheum Dis Clin North Am, 2009, 35(4): 745-757, vii-viii.
doi: 10.1016/j.rdc.2009.10.001
[14] Arnett FC, Edworthy SM, Bloch DA, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis[J]. Arthritis Rheum, 1988, 31(3):315-324.
doi: 10.1002/(ISSN)1529-0131
[15] Ostergaard M, Peterfy C, Conaghan P, et al. OMERACT rheumatoid arthritis magnetic resonance imaging studies. Core set of MRI acquisitions, joint pathology definitions, and the OMERACT RA-MRI scoring system[J]. J Rheumatol, 2003, 30(6):1385-1386.
[16] Bruyn GA, Hanova P, Iagnocco A, et al. Ultrasound definition of tendon damage in patients with rheumatoid arthritis. Results of a OMERACT consensus-based ultrasound score focusing on the diagnostic reliability[J]. Ann Rheum Dis, 2014, 73(11):1929-1934.
doi: 10.1136/annrheumdis-2013-203596
[17] Zeidler H. The need to better classify and diagnose early and very early rheumatoid arthritis[J]. J Rheumatol, 2012, 39(2):212-217.
doi: 10.3899/jrheum.110967
[18] Griffith JW, Sokol CL, Luster AD. Chemokines and chemokine receptors: Positioning cells for host defense and immunity[J]. Annu Rev Immunol, 2014, 32:659-702.
doi: 10.1146/annurev-immunol-032713-120145 pmid: 24655300
[19] Korniejewska A, McKnight AJ, Johnson Z, et al. Expression and agonist responsiveness of CXCR3 variants in human T lymphocytes[J]. Immunology, 2011, 132(4):503-515.
doi: 10.1111/j.1365-2567.2010.03384.x pmid: 21255008
[20] Schoenborn JR, Wilson CB. Regulation of interferon-gamma during innate and adaptive immune responses[J]. Adv Immunol, 2007, 96:41-101.
pmid: 17981204
[21] Farber JM. Mig and IP-10: CXC chemokines that target lymphocytes[J]. J Leukoc Biol, 1997, 61(3):246-257.
doi: 10.1002/jlb.1997.61.issue-3
[22] Kwak HB, Ha H, Kim HN, et al. Reciprocal cross-talk between RANKL and interferon-gamma-inducible protein 10 is responsible for bone-erosive experimental arthritis[J]. Arthritis Rheum, 2008, 58(5):1332-1342.
doi: 10.1002/(ISSN)1529-0131
[23] Kraan MC, Patel DD, Haringman JJ, et al. The development of clinical signs of rheumatoid synovial inflammation is associated with increased synjournal of the chemokine CXCL8 (interleukin-8)[J]. Arthritis Res, 2001, 3(1):65-71.
pmid: 11178128
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