Serum P55 and P75 Tumour Necrosis Factor Receptors As Markers of Disease Activity in Juvenile Chronic Arthritis

Overview

Journal Ann Rheum Dis

Specialty Rheumatology

Date 1996 Apr 1

PMID 8733441

Citations 10

Authors

M Gattorno

P Picco

A Buoncompagni

F Stalla

P Facchetti

M P Sormani

V Pistoia

Affiliations

Soon will be listed here.

Abstract

Objective: To determine the expression of tumour necrosis factor alpha (TNF alpha) and its soluble receptors (p55 and p75) in the sera and synovial fluid of patients with juvenile chronic arthritis (JCA), and their correlation with disease activity parameters.

Methods: Ninety eight sera from 45 patients with JCA (14 systemic, 12 polyarticular, 19 pauciarticular), 20 sera from age matched healthy controls, and five synovial fluids from five antinuclear antibody (ANA) positive pauciarticular JCA patients were tested for the presence of TNF alpha, soluble TNF receptors p55 and p75 (sTNFRp55, sTNFRp75), and interleukin-6 (IL-6) by an enzyme amplified sensitivity immunoassay. Physician global estimate of disease activity, weekly fever score and joint score, C reactive protein (CRP), erythrocyte sedimentation rate (ESR), and haemoglobin concentration were evaluated as parameters of disease activity. The expression of p55 and p75 on peripheral mononuclear cells (MNCs) from five patients with systemic JCA and synovial MNCs from five ANA positive patients with pauciarticular JCA was evaluated by flow cytometry.

Results: TNF alpha serum concentrations did not differ significantly between the patients with active JCA and the control group. No correlation was found between TNF alpha and parameters of disease activity, but both p55 and p75 showed a significant positive correlation with the physician global estimate of disease activity (p < 0.001), ESR (p < 0.001), CRP (p < 0.001), and serum concentrations of IL-6 (p < 0.001). Serum concentrations of haemoglobin correlated inversely with the concentrations of p55 and p75 (p < 0.001). Synovial lymphocytes selectively expressed the p75 surface receptor.

Conclusions: sTNFRp55 and sTNFRp75 each represent a sensitive marker of disease activity in JCA. Their increased expression in biological fluids may support the hypothesis that TNF alpha has a role in the pathogenesis of JCA.

Citing Articles

Inflammatory biomarkers predicting long-term remission and active disease in juvenile idiopathic arthritis: a population-based study of the Nordic JIA cohort.

Glerup M, Kessel C, Foell D, Berntson L, Fasth A, Myrup C RMD Open. 2024; 10(3).

PMID: 39242113 PMC: 11381635. DOI: 10.1136/rmdopen-2024-004317.

Soluble cytokine receptor levels in aqueous humour of patients with specific autoimmune uveitic entities: sCD30 is a biomarker of granulomatous uveitis.

Abu El-Asrar A, Berghmans N, Al-Obeidan S, Gikandi P, Opdenakker G, Van Damme J Eye (Lond). 2019; 34(9):1614-1623.

PMID: 31804623 PMC: 7608430. DOI: 10.1038/s41433-019-0693-7.

Characteristic elevation of soluble TNF receptor II : I ratio in macrophage activation syndrome with systemic juvenile idiopathic arthritis.

Shimizu M, Inoue N, Mizuta M, Nakagishi Y, Yachie A Clin Exp Immunol. 2017; 191(3):349-355.

PMID: 28815559 PMC: 5801501. DOI: 10.1111/cei.13026.

Comparison of drug and cell-based delivery: engineered adult mesenchymal stem cells expressing soluble tumor necrosis factor receptor II prevent arthritis in mouse and rat animal models.

Liu L, Wang G, Hendricks K, Lee K, Bohnlein E, Junker U Stem Cells Transl Med. 2013; 2(5):362-75.

PMID: 23592838 PMC: 3667563. DOI: 10.5966/sctm.2012-0135.

Tumor necrosis factor inhibitors in the management of juvenile idiopathic arthritis: an evidence-based review.

Shenoi S, Wallace C Paediatr Drugs. 2010; 12(6):367-77.

PMID: 21028916 DOI: 10.2165/11532610-000000000-00000.

References

Prieur A, KAUFMANN M, Griscelli C, Dayer J . Specific interleukin-1 inhibitor in serum and urine of children with systemic juvenile chronic arthritis. Lancet. 1987; 2(8570):1240-2. DOI: 10.1016/s0140-6736(87)91854-x. View

Cope A, Maini R . Soluble tumor necrosis factor receptors in arthritis. J Rheumatol. 1995; 22(3):382-4. View

Fiers W . Tumor necrosis factor. Characterization at the molecular, cellular and in vivo level. FEBS Lett. 1991; 285(2):199-212. DOI: 10.1016/0014-5793(91)80803-b. View

Keffer J, Probert L, Cazlaris H, Georgopoulos S, KASLARIS E, Kioussis D . Transgenic mice expressing human tumour necrosis factor: a predictive genetic model of arthritis. EMBO J. 1991; 10(13):4025-31. PMC: 453150. DOI: 10.1002/j.1460-2075.1991.tb04978.x. View

Brennan F, Maini R, Feldmann M . TNF alpha--a pivotal role in rheumatoid arthritis?. Br J Rheumatol. 1992; 31(5):293-8. DOI: 10.1093/rheumatology/31.5.293. View

Brennan F, Gibbons D, Mitchell T, Cope A, Maini R, Feldmann M . Enhanced expression of tumor necrosis factor receptor mRNA and protein in mononuclear cells isolated from rheumatoid arthritis synovial joints. Eur J Immunol. 1992; 22(7):1907-12. DOI: 10.1002/eji.1830220734. View

Williams R, Feldmann M, Maini R . Anti-tumor necrosis factor ameliorates joint disease in murine collagen-induced arthritis. Proc Natl Acad Sci U S A. 1992; 89(20):9784-8. PMC: 50217. DOI: 10.1073/pnas.89.20.9784. View

Cope A, Aderka D, Doherty M, Engelmann H, Gibbons D, Jones A . Increased levels of soluble tumor necrosis factor receptors in the sera and synovial fluid of patients with rheumatic diseases. Arthritis Rheum. 1992; 35(10):1160-9. DOI: 10.1002/art.1780351008. View

Roux-Lombard P, Punzi L, Hasler F, Bas S, Todesco S, Gallati H . Soluble tumor necrosis factor receptors in human inflammatory synovial fluids. Arthritis Rheum. 1993; 36(4):485-9. DOI: 10.1002/art.1780360408. View

10.

Woo P . Cytokines in childhood rheumatic diseases. Arch Dis Child. 1993; 69(5):547-9. PMC: 1029615. DOI: 10.1136/adc.69.5.547. View

11.

Higuchi M, Aggarwal B . TNF induces internalization of the p60 receptor and shedding of the p80 receptor. J Immunol. 1994; 152(7):3550-8. View

12.

Elliott M, Maini R, Feldmann M, Kalden J, Antoni C, Smolen J . Randomised double-blind comparison of chimeric monoclonal antibody to tumour necrosis factor alpha (cA2) versus placebo in rheumatoid arthritis. Lancet. 1994; 344(8930):1105-10. DOI: 10.1016/s0140-6736(94)90628-9. View

13.

Lepore L, Pennesi M, Saletta S, Perticarari S, Presani G, Prodan M . Study of IL-2, IL-6, TNF alpha, IFN gamma and beta in the serum and synovial fluid of patients with juvenile chronic arthritis. Clin Exp Rheumatol. 1994; 12(5):561-5. View

14.

Mangge H, Kenzian H, Gallistl S, Neuwirth G, Liebmann P, Kaulfersch W . Serum cytokines in juvenile rheumatoid arthritis. Correlation with conventional inflammation parameters and clinical subtypes. Arthritis Rheum. 1995; 38(2):211-20. DOI: 10.1002/art.1780380209. View

15.

Cope A, Aderka D, Wallach D, Kahan M, Chu N, Brennan F . Soluble TNF receptor production by activated T lymphocytes: differential effects of acute and chronic exposure to TNF. Immunology. 1995; 84(1):21-30. PMC: 1415193. View

16.

Madson K, Moore T, Lawrence 3rd J, Osborn T . Cytokine levels in serum and synovial fluid of patients with juvenile rheumatoid arthritis. J Rheumatol. 1994; 21(12):2359-63. View

17.

Brockhaus M, Schoenfeld H, Schlaeger E, Hunziker W, LESSLAUER W, Loetscher H . Identification of two types of tumor necrosis factor receptors on human cell lines by monoclonal antibodies. Proc Natl Acad Sci U S A. 1990; 87(8):3127-31. PMC: 53847. DOI: 10.1073/pnas.87.8.3127. View