Journal of Peking University(Health Sciences) ›› 2018, Vol. 50 ›› Issue (6): 975-980. doi: 10.19723/j.issn.1671-167X.2018.06.006

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Clinical significance of detection of soluble interleukin 2 receptor alpha chain in the assessment of rheumatoid arthritis disease activity

Jia jia XU1,Yan WANG1,(),He SUN1,Ru lin JIA2,Xue wu ZHANG1,(),Yang MENG1,Li li REN1,Xiao lin SUN2   

  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
  • Received:2018-07-10 Online:2018-12-18 Published:2018-12-18
  • Contact: Yan WANG,Xue wu ZHANG E-mail:wangyanh_1963@163.com;xuewu@sohu.com
  • Supported by:
    Supported by the National Natural Science Foundation of China(81471601)

Abstract:

Objective: To evaluate soluble interleukin-2 receptor alpha chain (sIL-2Rα, sCD25) in serum for the determination of rheumatoid arthritis (RA) activity.Methods:Peripheral blood was collected from 108 patients with RA, 39 patients with osteoarthritis (OA) and 50 healthy control subjects, and synovial fluids were from 40 patients with RA. The sera from the patients with RA, the disease control group (osteoarthritis), the healthy control group, and the synovial fluids of the RA patients were detected by enzyme-linked immunosorbent assay (ELISA).The clinical manifestations and laboratory parameters of the patients with RA were recorded and the correlation with the serum sCD25 level was analyzed.Results:The serum sCD25 concentration in RA group was (2 886±1 333) ng/L, the serum sCD25 concentration in OA group was (2 090±718) ng/L, and the serum sCD25 concentration in healthy group was (1 768±753) ng/L. The serum sCD25 level in the patients with RA was significantly higher than that in the disease controls and healthy controls (P<0.001). Sensitivity of serum sCD25 in the diagnosis of RA was 66.1% and specificity was 83.0%;serum sCD25 levels and erythrocyte sedimentation rate (r = 0.321, P = 0.001), C-reactive protein (r=0.446, P<0.001), DAS28 score (r = 0.324, P<0.001), joint tenderness count (r=0.203, P=0.024), D-dimer levels (r=0.383, P<0.001), age (r=0.24, P=0.007), IgG (r=0.207, P=0.028), HRF-IgG (r=0.345, P=0.034) showed a significant positive correlation, and disease duration (r=-0.206, P=0.021) showed a negative correlation with sCD25;In patients with rheumatoid arthritis, the positive rates of serum ESR, CRP, and sCD25 were 14.3% (2 cases), 14.3% (2 cases), and 71.4% (10 cases) in the low disease activity group. The positive rates of serum ESR, CRP and sCD25 in the moderate disease activity group were 94.2% (49 cases), 82.7% (43 cases), and 86.5% (45 cases). The positive rates of serum ESR, CRP, and sCD25 in the high disease activity group were 100% (42 cases), 95.2% (40 cases), and 90.5% (38 cases);36 cases of ESR and/or CRP were negative (about 33.3%) in 108 patients, serum sCD5 levels of 17 cases in these 36 cases (about 47.2%)increased, of which 14 cases (about 82.4%) had a DAS28 score higher than 3.2.Conclusion:The serum sCD25 has a high specificity for diagnosis of RA and a poor sensitivity. The serum level is closely related to the activity of RA, indicating that sCD25 may be involved in the inflammatory process of RA and may become a new inflammatory marker of RA.It is more meaningful for detection of serum sCD25 when RA is active, but ESR and/or CRP is negative.

Key words: Rheumatoid arthritis,activity, Interleukin 2 receptor α chain;, Sera sCD25, Erythrocyte sedimentation rate, C-reactive protein

CLC Number: 

  • R593.22

Figure 1

Analysis of sCD25 level in serum of patients with RA/OA and healthy human and joint fluid in partial patients with RAA, comparison of serum sCD25 levels in 108 patients with RA, 39 patients with OA, and 50 healthy individuals; B, comparison of sCD25 levels in serum of 108 patients with RA and 40 cases of RA joint fluid; C, comparison of sCD25 levels in serum of 10 RA patients and their joint effusion in the same period; RA, rheumatoid arthritis; OA, osteoarthritis; HC, healthy control; SF, joint effusion."

Table 1

Correlation between serum sCD25 levels and laboratory parameters in patients with RA"

Characteristics sCD25 in peripheral blood/(ng/L)
r P
Age/years 0.24 0.007*
Duration/years -0.206 0.021*
Tender joints, n 0.203 0.024*
Swollen joints, n 0.156 0.083
RF/(IU/mL) 0.110 0.248
ESR/(mm/h) 0.321 0.001*
CRP/(mg/L) 0.446 <0.001*
ACPA/(IU/mL) 0.043 0.659
RF-IgG/(IU/mL) 0.345 0.034*
GPI/(mg/L) 0.127 0.375
IgG/(g/L) 0.207 0.028*
IgA/(g/L) 0.159 0.092
IgM/(g/L) 0.069 0.467
C3/(g/L) 0.083 0.384
C4/(g/L) 0.059 0.537
ASO/(IU/mL) 0.048 0.614
D-dimer/(mg/L) 0.383 <0.001*
WBC/(×109/L) 0.214 0.017*
Neu/% 0.262 0.003*
DAS28 0.324 <0.001*

Table 2

Distribution of DAS28, ESR, CRP, and sCD25 in the low, medium, high disease activity groups (x-±s )"

Items LDA(n=14) MDA(n=52) HDA(n=42)
DAS28 3.11±0.05 4.46±0.51 5.67±0.32
ESR/(mm/h)* 12.50±5.58 32.62±23.18 62.19±28.45
CRP/(mg/L)* 17.00±2.05 19.65±25.16 50.26±38.16
sCD25/(ng/L)* 2 592±1 380 2 904±1 821 3 351±1 974

Figure 2

Comparison of ESR/CRP/SCD25 positive rates in disease activityA, LDA; B, MDA; C, HDA; LDA, low disease activity; MDA, moderate disease activity; HDA, high disease activity."

[1] Calabresi E, Petrelli F, Bonifacio AF , et al. One year in review 2018: pathogenesis of rheumatoid arthritis[J]. Clin Exp Rheumatol, 2018,36(2):175-184.
[2] Kumar LD, Karthik R, Gayathri N , et al. Advancement in contemporary diagnostic and therapeutic approaches for rheumatoid arthritis[J]. Biomed Pharmacother, 2016,79:52-61.
doi: 10.1016/j.biopha.2016.02.001 pmid: 27044812
[3] Chavele KM, Ehrenstein MR . Regulatory T-cells in systemic lupus erythematosus and rheumatoid arthritis[J]. FEBS Lett, 2011,585(23):3603-3610.
doi: 10.1016/j.febslet.2011.07.043 pmid: 21827750
[4] Boyman O, Kolios AG, Raeber ME . Modulation of T cell responses by IL-2 and IL-2 complexes[J]. Clin Exp Rheumatol, 2015,33(4 Suppl 92):S54-S57.
pmid: 26457438
[5] Howell MD, Diveley JP, Lundeen KA , et al. Limited T-cell receptor beta-chain heterogeneity among interleukin 2 receptor-positive synovial T cells suggests a role for superantigen in rheumatoid arthritis[J]. Proc Natl Acad Sci USA, 1991,88(23):10921-10925.
doi: 10.1073/pnas.88.23.10921
[6] Liao W, Lin JX, Leonard WJ . Interleukin-2 at the crossroads of effector responses, tolerance, and immunotherapy[J]. Immunity, 2013,38(1):13-25.
doi: 10.1016/j.immuni.2013.01.004 pmid: 3610532
[7] Setoguchi R, Hori S, Takahashi T , et al. Homeostatic maintenance of natural Foxp3(+) CD25(+) CD4(+) regulatory T cells by interleukin (IL)-2 and induction of autoimmune disease by IL-2 neutralization[J]. J Exp Med, 2005,201(5):723-735.
doi: 10.1084/jem.20041982
[8] Fulop T, Larbi A, Douziech N , et al. Cytokine receptor signalling and aging[J]. Mech Ageing Dev, 2006,127(6):526-537.
doi: 10.1016/j.mad.2006.01.025 pmid: 16530252
[9] Chrobak L . Clinical significance of soluble interleukin-2 receptor[J]. Acta Medica (Hradec Kralove), 1996,39(1):3-6.
pmid: 9106384
[10] Murakami S . Soluble interleukin-2 receptor in cancer[J]. Front Biosci, 2004,9:3085-3090.
doi: 10.2741/1461 pmid: 15353339
[11] Britsemmer K, Ursum J, Gerritsen M , et al. Validation of the 2010 ACR/EULAR classification criteria for rheumatoid arthritis: slight improvement over the 1987 ACR criteria[J]. Ann Rheum Dis, 2011,70(8):1468-1470.
doi: 10.1136/ard.2010.148619 pmid: 21586440
[12] 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
[13] Schett G, Gravallese E . Bone erosion in rheumatoid arthritis: mechanisms, diagnosis and treatment[J]. Nat Rev Rheumatol, 2012,8(11):656-664.
doi: 10.1038/nrrheum.2012.153 pmid: 23007741
[14] Lee YH, Bae SC, Song GG . Diagnostic accuracy of anti-MCV and anti-CCP antibodies in rheumatoid arthritis: A meta-analysis[J]. Z Rheumatol, 2015,74(10):911-918.
doi: 10.1007/s00393-016-0134-y pmid: 27312463
[15] Avouac J, Gossec L, Dougados M . Diagnostic and predictive value of anti-cyclic citrullinated proteinantibodies in rheumatoid arthritis: a systematic literature review[J]. Ann Rheum Dis, 2006,65(7):845-851.
[16] Sun J, Zhang Y, Liu L , et al. Diagnostic accuracy of combined tests of anti cyclic citrullinated peptide antibody and rheumatoid factor for rheumatoid arthritis: a meta-analysis[J]. Clin Exp Rheumatol, 2014,32(1):11-21.
doi: 10.1016/j.rbre.2014.02.013 pmid: 24050751
[17] Tak PP, Bresnihan B . The pathogenesis and prevention of joint damage in rheumatoid arthritis: advances from synovial biopsy and tissue analysis[J]. Arthritis Rheum, 2000,43(12):2619-2633.
doi: 10.1002/1529-0131(200012)43:123.0.CO;2-V pmid: 11145019
[18] Weyand CM, Goronzy JJ . Immunometabolism in early and late stages of rheumatoid arthritis[J]. Nat Rev Rheumatol, 2017,13(5):291-301.
doi: 10.1038/nrrheum.2017.49 pmid: 28360422
[19] Malmstrom V, Catrina AI, Klareskog L . The immunopathogenesis of seropositive rheumatoid arthritis: from triggering to targeting[J]. Nat Rev Immunol, 2017,17(1):60-75.
doi: 10.1038/nri.2016.124 pmid: 27916980
[20] Dlouhy I, Filella X, Rovira J , et al. High serum levels of soluble interleukin-2 receptor (sIL2-R), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF) are associated with adverse clinical features and predict poor outcome in diffuse large B-cell lymphoma[J]. Leuk Res, 2017,59:20-25.
doi: 10.1016/j.leukres.2017.05.014
[21] Akiyama M, Sasaki T, Kaneko Y , et al. Serum soluble interleukin-2 receptor is a useful biomarker for disease activity but not for differential diagnosis in IgG4-related disease and primary Sjögren’s syndrome adults from a defined population[J]. Clin Exp Rheumatol, 2018,112(36 Suppl 3):157-164.
pmid: 29465360
[22] Gundlach E, Hoffmann M M, Prasse A , et al. Interleukin-2 receptor and angiotensin-converting enzyme as markers for ocular sarcoidosis[J]. PLoS One, 2016,11(1):e147258.
doi: 10.1371/journal.pone.0147258 pmid: 4723126
[23] Nukui A, Masuda A, Abe H , et al. Increased serum level of soluble interleukin-2 receptor is associated with a worse response of metastatic clear cell renal cell carcinoma to interferon alpha and sequential VEGF-targeting therapy[J]. BMC Cancer, 2017,17(1):372.
doi: 10.1186/s12885-017-3369-3 pmid: 28545581
[24] Spadaro A, Taccari E, Riccieri V , et al. Relationship of soluble interleukin-2-receptor and interleukin-6 with class-specific rheumatoid factors during low-dose methotrexate treatment in rheumatoid arthritis[J]. Rev Rhum Engl Ed, 1997,64(2):89-94.
doi: 10.1016/S0950-3579(97)80028-3 pmid: 9085442
[25] Knevel R, de Rooy DP, Zhernakova A , et al. Association of variants in IL2RA with progression of joint destruction in rheumatoid arthritis[J]. Arthritis Rheum, 2013,65(7):1684-1693.
doi: 10.1002/art.37938
[26] van Steenbergen HW, van Nies JA, Ruyssen-Witrand A , et al. IL2RA is associated with persistence of rheumatoid arthritis[J]. Arthritis Res Ther, 2015,17:244.
doi: 10.1186/s13075-015-0739-6 pmid: 4563834
[27] Turka LA, Walsh PT . IL-2 signaling and CD4+CD25+Foxp3+regulatory T cells[J]. Front Biosci, 2008,13:1440-1446.
doi: 10.2741/2773 pmid: 17981641
[28] von Spee-Mayer C, Siegert E, Abdirama D , et al. Low-dose interleukin-2 selectively corrects regulatory T cell defects in patients with systemic lupus erythematosus[J]. Ann Rheum Dis, 2016,75(7):1407-1415.
doi: 10.1136/annrheumdis-2015-207776 pmid: 26324847
[29] Matsuoka K, Koreth J, Kim HT , et al. Low-dose interleukin-2 therapy restores regulatory T cell homeostasis in patients with chronic graft-versus-host disease[J]. Sci Transl Med, 2013,5(179):143r-179r.
doi: 10.1126/scitranslmed.3005265 pmid: 368651795284151236538681511
[30] Gaujoux-Viala C, Mouterde G, Baillet A , et al. Evaluating disease activity in rheumatoid arthritis: which composite index is best? A systematic literature analysis of studies comparing the psychometric properties of the DAS, DAS28, SDAI and CDAI[J]. Joint Bone Spine, 2012,79(2):149-155.
doi: 10.1016/j.jbspin.2011.04.008
[31] Aletaha D, Nell VP, Stamm T , et al. Acute phase reactants add little to composite disease activity indices for rheumatoid arthritis: validation of a clinical activity score[J]. Arthritis Res Ther, 2005,7(4):R796-R806.
doi: 10.1186/ar1740 pmid: 1175030
[32] Stojan G, Fang H, Magder L , et al. Erythrocyte sedimentation rate is a predictor of renal and overall SLE disease activity[J]. Lupus, 2013,22(8):827-834.
doi: 10.1177/0961203313492578
[33] Orr C K, Najm A, Young F , et al. The utility and limitations of CRP, ESR and DAS28-CRP in appraising disease activity in rheumatoid arthritis[J]. Front Med (Lausanne), 2018,5:185.
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