Journal of Peking University(Health Sciences) >
Expression of plasma Dickkopf-1 in patients with rheumatoid arthritis and its correlation with peripheral blood T cell subsets
Received date: 2020-03-16
Online published: 2021-04-21
Supported by
National Natural Science Foundation of China(81771678);Key Scientific and Technological Project of Education Department of Henan Province(19A320016)
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
Di CAO , Yan WANG , Liu-qing WANG , Xiao-lin SUN , Fei HUANG , Yang MENG , Li-li REN , Xue-wu ZHANG . Expression of plasma Dickkopf-1 in patients with rheumatoid arthritis and its correlation with peripheral blood T cell subsets[J]. Journal of Peking University(Health Sciences), 2021 , 53(2) : 255 -260 . DOI: 10.19723/j.issn.1671-167X.2021.02.004
| [1] | Smolen JS, Aletaha D, Mcinnes IB. Rheumatoid arthritis[J]. Lancet, 2016,388(10055):2023-2038. |
| [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. |
| [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. |
| [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. |
| [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. |
| [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. |
| [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. |
/
| 〈 |
|
〉 |