Journal of Peking University (Health Sciences) ›› 2021, Vol. 53 ›› Issue (2): 255-260. doi: 10.19723/j.issn.1671-167X.2021.02.004

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Expression of plasma Dickkopf-1 in patients with rheumatoid arthritis and its correlation with peripheral blood T cell subsets

CAO Di1,WANG Yan1,Δ(),WANG Liu-qing1,SUN Xiao-lin2,HUANG Fei3,MENG Yang1,REN Li-li1,ZHANG Xue-wu2,Δ()   

  1. 1. Department of Rheumatology and Immunology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, China
    2. Department of Rheumatology and Immunology, Peking University People’s Hospital, Beijing 100044, China
    3. Department of Rheumatology and Immunology,Affiliated Hospital of Zunyi Medical University, Zunyi 563000, Guizhou, China
  • Received:2020-03-16 Online:2021-04-18 Published:2021-04-21
  • Contact: Yan WANG,Xue-wu ZHANG E-mail:wangyanh_1963@163.com;xuewulore@163.com
  • Supported by:
    National Natural Science Foundation of China(81771678);Key Scientific and Technological Project of Education Department of Henan Province(19A320016)

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Abstract:

Objective: To detect the levels of Dickkopf-1 (DKK-1) in the plasma of patients with rheumatoid arthritis (RA), and to analyze their correlation with peripheral blood T cell subsets and clinical indicators. Methods: Enzyme-linked immunosorbent assay (ELISA) was used to detect plasma DKK-1 levels in 32 RA patients and 20 healthy controls, and to record the various clinical manifestations and laboratory indicators of the RA patients, and flow cytometry to detect peripheral blood T cell subsets in the RA patients (Including Treg, nTreg, aTreg, sTreg, Teff, Tfh, CD4+CD161+T, CD8+T, CD8+CD161+T cells). The plasma DKK-1 levels between the two groups were ompared, and its correlation with peripheral blood T cell subsets and clinical indicators analyzed. Results: (1) The plasma DKK-1 concentration of the RA patients was (124.97±64.98) ng/L. The plasma DKK-1 concentration of the healthy control group was (84.95±13.74) ng/L. The plasma DKK-1 level of the RA patients was significantly higher than that of the healthy control group (P<0.05), and the percentage of CD8+CD161+T cells in the peripheral blood of the RA patients was significantly higher than that of the healthy control group (P<0.05). (2) The plasma DKK-1 level was positively correlated with erythrocyte sedimentation rate (r=0.406, P=0.021),DAS28 score (r=0.372, P=0.036), immunoglobulin G(r=0.362, P=0.042), immunoglobulin A(r=0.377, P=0.033) ; it had no correlation with age, course of disease, C-reactive protein, rheumatoid factor, anti-cyclic citrullinated peptide antibody, immunoglobulin M, complement C3, complement C4, white blood cell, neutrophil ratio. (3) The plasma DKK-1 level in the RA patients was positively correlated with the percentage of peripheral blood CD161+CD8+T cells (r=0.413, P=0.019);it had no correlation with Treg, nTreg, aTreg, sTreg, Teff, Tfh, CD4+CD161+T, CD8+T cells. (4) The percentage of CD161+CD8+T cells was negatively correlated with erythrocyte sedimentation rate (r=-0.415, P=0.004), C-reactive protein (r=-0.393, P=0.007), DAS28 score(r=-0.392, P=0.007),rheumatoid factor (r=-0.535, P<0.001), anti-citrullinated protein antibody (r=-0.589, P<0.001), immunoglobulin G(r=-0.368, P=0.012) immunoglobulin M (r=-0.311, P=0.035); it had no correlation with age, disease course, immunoglobulin A, complement C3, complement C4,white blood cell,and neutrophil ratio. Conclusion: RA patients’ plasma DKK-1 levels and the percentage of CD8+CD161+T cells in T cell subsets in peripheral blood increase, which may be related to the secretion of proinflammatory cytokines in patients; DKK-1 is involved in the regulation of bone homeostasis and can be used as a marker of bone destruction in RA.

Key words: Rheumatoid arthritis, Dickkopf-1, T cells

CLC Number: 

  • R593.2

Table 1

Basic clinical data of study subjects"

Characteristics RA (n=32)
Age/years, $\bar{x} \pm s$ 63.09 ±11.07
Duration/years, M (Min, Max) 10.0 (5.0, 17.3)
ESR/(mm/h), $\bar{x} \pm s$ 47.53±22.76
CRP/(mg/L), M (Min, Max) 24.4 (7.2, 56.4)
DAS28, $\bar{x} \pm s$ 5.29±1.40
RF/(IU/mL), M (Min, Max) 350.0 (134.3, 657.5)
CCP/(U/mL), M (Min, Max) 178.8 (134.3, 230.7)
IgG/(g/L), $\bar{x} \pm s$ 14.06±3.93
IgA/(g/L), $\bar{x} \pm s$ 3.35±1.28
IgM/(g/L), $\bar{x} \pm s$ 1.37±0.70
C3/(g/L), $\bar{x} \pm s$ 0.93±0.24
C4/(g/L), $\bar{x} \pm s$ 0.18±0.08
WBC/(×109/L), $\bar{x} \pm s$ 6.61±2.33
Neu/%, $\bar{x} \pm s$ 63.92±13.15

Figure 1

Levels of plasma DKK-1 and percentage of peripheral blood CD8+CD161+T cells in RA group and healthy control group A, Plasma DKK-1 levels in RA and healthy controls; B, Percentage of CD8+CD161+T cells in peripheral blood of RA group and healthy control group.RA, rheumatoid arthritis; HC, healthy controls;DKK-1,Dickkopf-1."

Figure 2

Differences in peripheral blood T Cell subsets in DKK-1 elevated group, DKK-1 normal group, and healthy control group A,Treg percentage;B,nTreg percentage;C,aTreg percentage; D,sTreg percentage;E,Teff percentage;F,Tfh percentage; G,CD4+CD161+T cell percentage;H,CD8+T cell percentage;I,CD8+CD161+T cell percentage;HC, healthy controls; DKK-1, Dickkopf-1."

Figure 3

Correlation between plasma DKK-1 levels and peripheral blood CD8+ CD161+T cells in RA patients DKK-1,Dickkopf-1."

[1] Smolen JS, Aletaha D, Mcinnes IB. Rheumatoid arthritis[J]. Lancet, 2016,388(10055):2023-2038.
pmid: 27156434
[2] Lee GR. The balance of Th17 versus Treg cells in autoimmunity[J]. Int J Mol Sci, 2018,19(3):730.
[3] Chae WJ, Park JH, Henegariu O, et al. Membrane-bound Dickkopf-1 in Foxp3+ regulatory T cells suppresses T-cell-mediated autoimmune colitis[J]. Immunology, 2017,152(2):265-275.
pmid: 28556921
[4] Chae WJ, Ehrlich AK, Chan PY, et al. The Wnt antagonist Dickkopf-1 promotes pathological type 2 cell-mediated Inflammation[J]. Immunity, 2016,44(2):246-258.
pmid: 26872695
[5] 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]. Ann Rheum Dis, 2010,62(9):2569-2581.
[6] Glinka A, Wu W, Delius H, et al. Dickkopf-1 is a member of a new family of secreted proteins and functions in head induction[J]. Nature, 1998,391(6665):357-362.
pmid: 9450748
[7] Fujita K, Janz S. Attenuation of WNT signaling by DKK-1 and -2 regulates BMP2-induced osteoblast differentiation and expression of OPG, RANKL and M-CSF[J]. Mol Cancer, 2007,6(1):71.
[8] Diarra D, Stolina M, Polzer K, et al. Dickkopf-1 is a master regulator of joint remodeling[J]. Nat Med, 2007,13(2):156-163.
pmid: 17237793
[9] Gómez-Vaquero C, Martín I, Loza E, et al. Effect of osteoprotegerin and Dickkopf-related protein 1 on radiological progression in tightly controlled rheumatoid arthritis[J]. PLoS One, 2016,11(12):e0166691.
[10] Rout N. Enhanced Th1/Th17 functions of CD161+CD8+T cells in mucosal tissues of rhesus macaques[J]. PLoS One, 2016,11(6):e0157407.
pmid: 27309719
[11] Mitsuo A, Morimoto S, Nakiri Y, et al. Decreased CD161+CD8+ T cells in the peripheral blood of patients suffering from rheumatic diseases[J]. Rheumatology (Oxford), 2006,45(12):1477-1484.
[12] Nicol B, Salou M, Vogel I, et al. An intermediate level of CD161 expression defines a novel activated, inflammatory, and pathogenic subset of CD8+T cells involved in multiple sclerosis[J]. J Autoimmun, 2018,88:61-74.
doi: 10.1016/j.jaut.2017.10.005
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