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Evaluation of soluble tumor necrosis factor (TNF) receptors and TNF receptor antibodies in patients with systemic lupus erythematodes, progressive systemic sclerosis, and mixed connective tissue disease

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Abstract

Two TNF binding proteins have been characterized as soluble fragments of TNF receptors. We measured the plasma concentrations of soluble type A (p75) and type B (p55) TNF receptors in patients with systemic lupus erythematodes (SLE), progressive systemic sclerosis (PSS), and mixed connective tissue disease (MCTD). In SLE and PSS patients plasma concentrations of both types of TNF receptors and in MCTD patients type A TNF receptors were significantly elevated compared to controls. Plasma concentrations of both soluble TNF receptors were highly correlated in SLE, PSS, and MCTD patients, indicating a possible coregulation of both TNF receptors. In contrast, soluble interleukin 2 receptor (sCD 25) plasma concentrations were not correlated and seem to be an independent parameter. The soluble forms of the TNF receptors neutralize TNF in cytotoxicity assays and are functionally active as TNF antagonists. In one patient with SLE, autoantibodies against type A TNF receptors were detected, TNFα, and TNFβ did not interfere with the autoantibody binding to the receptor.

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References

  1. Sherry B, Cerami A: Cachectin/tumor necrosis factor exerts endocrine, paraerine and autocrine control of inflammatory responses. J Cell Biol 107:1269–1275, 1988

    Google Scholar 

  2. Linker-Israeli M, Deans RJ, Wallace DJ, Prehn J, Ozeri-Chen T, Klinenberg JR: Elevated levels of endogenous IL-6 in systemic lupus erythematosus. A putative role in pathogenesis. J Immunol 147:117–123, 1991

    Google Scholar 

  3. Kahaleh MB: Soluble immunologic products in scleroderma sera. Clin Immunol Immunopathol 58:139–145, 1991

    Google Scholar 

  4. Miossec P: The role of interleukin 1 in the pathogenesis of rheumatoid arthritis. Clin Exp Rheumatol 5:305–308, 1987

    Google Scholar 

  5. Maury CP, Teppo AM: Tumor necrosis factor in the serum of patients with systemic lupus erythematosus. Arth Rheum 32:146–152, 1989

    Google Scholar 

  6. Yocum DE, Esparza L, Dubry S, Benjamin JB, Volz R, Scuderi P: Characteristics of tumor necrosis factor production in rheumatoid arthritis. Cell Immunol 122:131–145, 1989

    Google Scholar 

  7. Saxne T, Palladino MA, Heinegard D, Talal N, Wollheim FA: Detection of tumor necrosis factor α but not tumor necrosis factor β in rheumatoid arthritis synovial fluid and serum. Arth Rheum 31:1041–1045, 1988

    Google Scholar 

  8. Husby G, Williams RC: Synovial localization of tumor necrosis factor in patients with rheumatoid arthritis. J Autoimmun 1:363–371, 1988

    Google Scholar 

  9. Engelmann H, Aderka D, Rubinstein M, Rotman D, Wallach DA: Tumor necrosis factor-binding protein purified to homogeneity from human urine protects cells from tumor necrosis factor toxicity. J Biol Chem 264:11974–11980, 1989

    Google Scholar 

  10. Olson I, Lantz M, Nilsson E, Peetre C, Thysell H, Grubb A, Adolf G: Isolation and characterization of a tumor necrosis factor binding protein from urine. Eur J Haematol 42:270–275, 1989

    Google Scholar 

  11. Seckinger P, Isaaz S, Dayer JM: Purification and characterization of a specific tumor necrosis factor alpha inhibitor. J Biol Chem 264:11966–11973, 1989

    Google Scholar 

  12. Brockhaus M, Schoenfeld HJ, Schlaeger EJ, 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 USA 87:3127–3132, 1990

    Google Scholar 

  13. Hohmann HP, Remy R, Brockhaus M, van Loon AP: Two different cell types have different major receptors for human tumor necrosis factor (TNF alpha). J Biol Chem 264:14927–14933, 1989

    Google Scholar 

  14. Loetscher HR, Pan YE, Lahm HW, Gentz R, Brockhaus M, Tabuchi H, Lesslauer W: Molecular cloning and expression of the human 55 kD tumor necrosis factor receptor. Cell 61:351–357, 1990

    Google Scholar 

  15. Schall TJ, Lewis M, Koller KJ, Lee A, Rice GC, Wong W, Gatanaga T, Granger GA, Lentz R, Raab H, Kohr WJ, Goeddel DV: Molecular cloning and expression of a receptor for human tumor necrosis factor. Cell 61:361–367, 1990

    Google Scholar 

  16. Smith CA, Davis T, Anderson D, Solam L, Beckmann MP, Jerzy R, Dower SK, Cosman D, Goodwin RG: A receptor for tumor necrosis factor defines an unusual family of cellular and viral proteins. Science (Wash. DC) 248:1019–1023, 1990

    Google Scholar 

  17. Iton N, Yonehara S, Ishii A, Yonehara M, Mizushima S, Hase A, Seto Y, Nagata S: The polypeptide encoded by the cDNA for human cell surface antigen Fas can mediate apoptosis. Cell 155:233–239, 1991

    Google Scholar 

  18. Dembic Z, Loetscher H, Gubler U, Pan Y, Lahm H, Gentz R, Brockhaus M, Lesslauer W: Two human TNF receptors have similar extracellular, but distinct intracellular, domain sequences. Cytokine 2:231–237, 1990

    Google Scholar 

  19. Porteu F, Nathan C: Shedding of tumor necrosis factor receptors by activated human neutrophils. J Exp Med 172:599–607, 1990

    Google Scholar 

  20. Porteu F, Brockhaus M, Wallach D, Engelmann H, Nathan CF: Human neutrophil elastase releases a ligand binding fragment from the 75 kD tumor necrosis factor receptor. Comparison with proteolytic activity responsible for shedding of TNF receptors from stimulated neutrophils. J Biol Chem 266:18846–18852, 1991

    Google Scholar 

  21. Digel W, Porzsolt F, Schmid M, Herrmann F, Lesslauer W, Brockhaus M: High levels of circulating soluble receptors for tumor necrosis factor in B-cell malignancies. J Clin Invest (in press), 1992

  22. Heilig B, Wermann M, Gallati H, Brockhaus M, Berke B, Egen O, Pezzutto A, Hunstein W: Elevated TNF receptors plasma concentrations in patients with rheumatoid arthritis. Clin Invest 70:22–28, 1992

    Google Scholar 

  23. Aderka D, Engelmann H, Hornik V, Skornick Y, Levo Y, Wallach D, Kushtai G: Increased serum levels of soluble receptors for tumor necrosis factor in cancer patients. Cancer Res 51:5602–5607, 1991

    Google Scholar 

  24. Lantz M, Gullbverg U, Nilsson E, Olsson I: Characterization in vitro of a human tumor necrosis factor-binding protein. J Clin Invest 86:1396–1402, 1990

    Google Scholar 

  25. Adolf GR, Apfler I: A monoclonal antibody-based enzyme immuno assay for quantitation of human tumor necrosis factor binding protein I, a soluble fragment of the 60 kDa TNF receptor, in biological fluids. J Immunol Methods 143:127–136, 1991

    Google Scholar 

  26. Symons JA, Wood NC, Giovine FS, Duff GW: Soluble II-2 receptor in rheumatoid arthritis. J Immunol 141:2612–2619, 1988

    Google Scholar 

  27. Semenzato G, Bambara LM, Biasi A, Frigo A, Vinante F, Zuppini B, Trentin L, Feruglio C, Chilosi M, Pizzolo G: Increased serum levels of soluble interleukin-2 receptor in patients with systemic lupus erythematosus and rheumatoid arthritis. J Clin Immunol 8:447–453, 1988

    Google Scholar 

  28. Degiannis D, Seibold JR, Czarnecki M, Raskova J, Raska KJ Jr: Soluble interleukin-2 receptors in patients with systemic sclerosis: Clinical and laboratory correlations. Arth Rheum 33:375–380, 1990

    Google Scholar 

  29. Rubin LA: The soluble interleukin-2 receptor in rheumatic disease. Arth Rheum 33:1145–1146, 1990

    Google Scholar 

  30. Urban JL, Shepard HM, Rothstein JL, Sugarman BJ, Schreiber H: Tumor necrosis factor: A potent effector molecule for tumor cell killing by activated macrophages. Proc Natl Acad Sci USA 83:5233–5238, 1986

    Google Scholar 

  31. Mosman T: Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxic assays. J Immunol Methods 65:55–60, 1983

    Google Scholar 

  32. Jacob CO, Zdenka F, Lewis GD, Koo M, Hansen JA, McDevitt HO: Heritable major histocompatibility complex class II-associated differences in production of tumor necrosis factor α: Relevance to genetic predisposition to systemic lupus erythematosus. Proc Natl Acad Sci USA 87:1233–1238, 1990

    Google Scholar 

  33. Jacob CO, McDevitt HO: Tumour necrosis factor-α in murine autoimmune “lupus” nephritis. Nature 331:356–359, 1988

    Google Scholar 

  34. Miyagi J, Minato N, Sumiya M, Kasahara T, Kano S: Two types of antibodies inhibiting interleukin 2 production by normal lymphocytes in patients with systemic lupus erythematosus. Arth Rheum 32:1356–1362, 1989

    Google Scholar 

  35. Espevik T, Brockhaus M, Loetscher H, Nonstad U, Shalaby R: Characterization of binding and biological effects of monoclonal antibodies against a human tumor necrosis factor receptor. J Exp Med 171:415–422, 1990

    Google Scholar 

  36. Engelmann H, Holtmann H, Brakebusch C, Avni YS, Sarov I, Nophar Y, Hadas E, Leitner O, Wallach D: Antibodies to a soluble form of tumor necrosis factor have TNF-like activity. J Biol Chem 265:14497–14504

  37. Shalaby MR, Sundan A, Loetscher H, Brockhaus M, Lesslauer W, Espevik T: Binding and regulation of cellular functions by monoclonal antibodies against human tumor necrosis factor receptors. J Exp Med 172:1517–1520, 1990

    Google Scholar 

  38. Bendtzen K, Svenson M, Jonsson V, Hippe E: Autoantibodies to cytokines-friends or foes? Immunol Today 11:167–169, 1990

    Google Scholar 

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Heilig, B., Fiehn, C., Brockhaus, M. et al. Evaluation of soluble tumor necrosis factor (TNF) receptors and TNF receptor antibodies in patients with systemic lupus erythematodes, progressive systemic sclerosis, and mixed connective tissue disease. J Clin Immunol 13, 321–328 (1993). https://doi.org/10.1007/BF00920240

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