Skip to main content
Annals of the Rheumatic Diseases logoLink to Annals of the Rheumatic Diseases
. 1996 Apr;55(4):243–247. doi: 10.1136/ard.55.4.243

Serum p55 and p75 tumour necrosis factor receptors as markers of disease activity in juvenile chronic arthritis.

M Gattorno 1, P Picco 1, A Buoncompagni 1, F Stalla 1, P Facchetti 1, M P Sormani 1, V Pistoia 1
PMCID: PMC1010145  PMID: 8733441

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.

Full text

PDF
243

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Brennan F. M., Gibbons D. L., Mitchell T., Cope A. P., Maini R. N., 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 Jul;22(7):1907–1912. doi: 10.1002/eji.1830220734. [DOI] [PubMed] [Google Scholar]
  2. Brennan F. M., Maini R. N., Feldmann M. TNF alpha--a pivotal role in rheumatoid arthritis? Br J Rheumatol. 1992 May;31(5):293–298. doi: 10.1093/rheumatology/31.5.293. [DOI] [PubMed] [Google Scholar]
  3. Brockhaus M., Schoenfeld H. J., Schlaeger E. J., 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 Apr;87(8):3127–3131. doi: 10.1073/pnas.87.8.3127. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cope A. P., Aderka D., Doherty M., Engelmann H., Gibbons D., Jones A. C., Brennan F. M., Maini R. N., Wallach D., Feldmann M. Increased levels of soluble tumor necrosis factor receptors in the sera and synovial fluid of patients with rheumatic diseases. Arthritis Rheum. 1992 Oct;35(10):1160–1169. doi: 10.1002/art.1780351008. [DOI] [PubMed] [Google Scholar]
  5. Cope A. P., Aderka D., Wallach D., Kahan M., Chu N. R., Brennan F. M., Feldmann M. Soluble TNF receptor production by activated T lymphocytes: differential effects of acute and chronic exposure to TNF. Immunology. 1995 Jan;84(1):21–30. [PMC free article] [PubMed] [Google Scholar]
  6. Cope A. P., Maini R. N. Soluble tumor necrosis factor receptors in arthritis. J Rheumatol. 1995 Mar;22(3):382–384. [PubMed] [Google Scholar]
  7. Elliott M. J., Maini R. N., Feldmann M., Kalden J. R., Antoni C., Smolen J. S., Leeb B., Breedveld F. C., Macfarlane J. D., Bijl H. Randomised double-blind comparison of chimeric monoclonal antibody to tumour necrosis factor alpha (cA2) versus placebo in rheumatoid arthritis. Lancet. 1994 Oct 22;344(8930):1105–1110. doi: 10.1016/s0140-6736(94)90628-9. [DOI] [PubMed] [Google Scholar]
  8. Fiers W. Tumor necrosis factor. Characterization at the molecular, cellular and in vivo level. FEBS Lett. 1991 Jul 22;285(2):199–212. doi: 10.1016/0014-5793(91)80803-b. [DOI] [PubMed] [Google Scholar]
  9. Higuchi M., Aggarwal B. B. TNF induces internalization of the p60 receptor and shedding of the p80 receptor. J Immunol. 1994 Apr 1;152(7):3550–3558. [PubMed] [Google Scholar]
  10. Keffer J., Probert L., Cazlaris H., Georgopoulos S., Kaslaris E., Kioussis D., Kollias G. Transgenic mice expressing human tumour necrosis factor: a predictive genetic model of arthritis. EMBO J. 1991 Dec;10(13):4025–4031. doi: 10.1002/j.1460-2075.1991.tb04978.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. 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 Sep-Oct;12(5):561–565. [PubMed] [Google Scholar]
  12. Madson K. L., Moore T. L., Lawrence J. M., 3rd, Osborn T. G. Cytokine levels in serum and synovial fluid of patients with juvenile rheumatoid arthritis. J Rheumatol. 1994 Dec;21(12):2359–2363. [PubMed] [Google Scholar]
  13. Mangge H., Kenzian H., Gallistl S., Neuwirth G., Liebmann P., Kaulfersch W., Beaufort F., Muntean W., Schauenstein K. Serum cytokines in juvenile rheumatoid arthritis. Correlation with conventional inflammation parameters and clinical subtypes. Arthritis Rheum. 1995 Feb;38(2):211–220. doi: 10.1002/art.1780380209. [DOI] [PubMed] [Google Scholar]
  14. Prieur A. M., Kaufmann M. T., Griscelli C., Dayer J. M. Specific interleukin-1 inhibitor in serum and urine of children with systemic juvenile chronic arthritis. Lancet. 1987 Nov 28;2(8570):1240–1242. doi: 10.1016/s0140-6736(87)91854-x. [DOI] [PubMed] [Google Scholar]
  15. Roux-Lombard P., Punzi L., Hasler F., Bas S., Todesco S., Gallati H., Guerne P. A., Dayer J. M. Soluble tumor necrosis factor receptors in human inflammatory synovial fluids. Arthritis Rheum. 1993 Apr;36(4):485–489. doi: 10.1002/art.1780360408. [DOI] [PubMed] [Google Scholar]
  16. Williams R. O., Feldmann M., Maini R. N. Anti-tumor necrosis factor ameliorates joint disease in murine collagen-induced arthritis. Proc Natl Acad Sci U S A. 1992 Oct 15;89(20):9784–9788. doi: 10.1073/pnas.89.20.9784. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Woo P. Cytokines in childhood rheumatic diseases. Arch Dis Child. 1993 Nov;69(5):547–549. doi: 10.1136/adc.69.5.547. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Annals of the Rheumatic Diseases are provided here courtesy of BMJ Publishing Group

RESOURCES