Journal of Clinical Immunology

, Volume 8, Issue 6, pp 447–452

Increased serum levels of soluble interleukin-2 receptor in patients with systemic lupus erythematosus and rheumatoid arthritis

  • G. Semenzato
  • L. M. Bambara
  • D. Biasi
  • A. Frigo
  • F. Vinante
  • B. Zuppini
  • L. Trentin
  • C. Feruglio
  • M. Chilosi
  • G. Pizzolo
Original Articles

Abstract

In this study we investigated the serum levels of a released soluble form of the interleukin-2 receptor (sIL-2R) in 42 patients with rheumatoid arthritis and in 12 cases of systemic lupus erythematosus. Data were evaluated in relationship to the clinical phase and compared with those observed in normal controls (N=56) and in osteoarthritis (N = 7). Increased levels were observed in both rheumatoid arthritis (mean ± SE, 604±49 U/ml) and systemic lupus erythematosus (1438±481 U/ml). These values were significantly higher than in control (256±15 U/ml;P<0.001) and in osteoarthritis (298±33 U/ml;P<0.001) groups. In addition, the highest values were associated with the active phases of both rheumatoid arthritis (active vs inactive, 771±78 vs 451±39 U/ml;P<0.001) and systemic lupus erythematosus (active vs inactive, 2108±489 vs 499±75 U/ml;P<0.001). Our findings suggest that the detection of sIL-2R in rheumatoid arthritis and in systemic lupus erythematosus may represent a good marker of disease activity, which indirectly indicates the ongoing activation and/or proliferation of immunoreactive cells which are involved in the pathogenetic events of these autoimmune conditions.

Key words

Soluble interleukin-2 receptor systemic lupus erythematosus rheumatoid arthritis 

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References

  1. 1.
    Shoenfeld Y, Schwartz RS: Immunologic and genetic factors in autoimmune diseases. N Engl J Med 311:1019–1029, 1984Google Scholar
  2. 2.
    Decker JL, Malone DG, Haraoui B, Wahl SM, Schrieber L, Klippel JH, Steinberg AD, Wilder RL: Rheumatoid arthritis: Evolving concepts of pathogenesis and treatment. Ann Intern Med 10:810–824, 1984Google Scholar
  3. 3.
    Zvaifler NJ: Immunopathology of inflammatory diseases. Rheumatoid arthritis as an example. Adv Inflamm Res 7:1–11, 1984Google Scholar
  4. 4.
    Theofilopoulus NA, Dixon FJ: Murine models of systemic lupus erythematosus. Adv Immunol 37:269–390, 1985Google Scholar
  5. 5.
    Janossy G, Duke O, Poulter LW, Panayi G, Boffil M, Goldstein G: Rheumatoid arthritis: A disease of T-lymphocyte/macrophage immunoregulation. Lancet 2:839–842, 1981Google Scholar
  6. 6.
    Alcocer-Varela J, Alarcon-Segovia D: Decreased production of and response to interleukin 2 by cultured lymphocytes from systemic lupus crythematosus. J Clin Invest 69:1388–1392, 1982Google Scholar
  7. 7.
    Miyasaka N, Nakamura T, Russel IJ, Talal N: Interleukin 2 deficiencies in rheumatoid arthritis and systemic lupus erythematosus. Clin Immunol Immunopathol 31:109–117, 1984Google Scholar
  8. 8.
    Murakava Y, Takada S, Ueda Y, Suzuki N, Hoshino T, Sakane T: Characterization of T lymphocyte subpopulations responsible for deficient interleukin 2 activity in patients with systemic lupus erythematosus. J Immunol 134:187–195, 1985Google Scholar
  9. 9.
    Combe B, Pope RM, Fischbach M, Darnell B, Baron S, Talal N: Interleukin 2 in rheumatoid arthritis: Production of and response to interleukin 2 in rheumatoid synovial fluid, synovial tissue and peripheral blood. Clin Exp Immunol 59:520–528, 1985Google Scholar
  10. 10.
    Dauphinee MJ, Kipper SB, Wofsy D, Talal N: Interleukin-2 deficiency is a common feature of autoimmune mice. J Immunol 127:2483–2487, 1981Google Scholar
  11. 11.
    Altman A, Theofilopoulos AN, Weiner R, Katz DH, Dixon FJ: Analysis of T cell function in autoimmune murine strains. Defects in production of and responsiveness to interleukin 2. J Exp Med 154:791–808, 1981Google Scholar
  12. 12.
    Cantrell DA, Smith K: The interleukin 2 T cell system. A new cell growth model. Science 224:1312–1316, 1984Google Scholar
  13. 13.
    Robb RJ, Greene WC, Rusk CM: Low and high affinity cellular receptor for interleukin 2. Implication for the level of Tac antigen. J Exp Med 160:1126–1146, 1985Google Scholar
  14. 14.
    Tsudo M, Uchiyama T, Uchino H: Expression of Tac antigen on activated normal human B cells. J Exp Med 160:612–617, 1984Google Scholar
  15. 15.
    Herrmann F, Cannistra M, Levine H, Griffin JD: Expression of interleukin 2 by gamma interferon-induced human leukemic and normal monocyte cells. J Exp Med 162:1111–1116, 1985Google Scholar
  16. 16.
    Greene WC, Leonard WJ, Depper JM, Nelson DL, Waldmann TA: The human interleukin-2 receptor: Normal and abnormal expression in T cells and in leukemias induced by the human T-lymphotropic retroviruses. Ann Intern Med 105:560–572, 1986Google Scholar
  17. 17.
    Smith KA: The bimolecular structure of the interleukin 2 receptor. Immunol Today 9:36–37, 1988Google Scholar
  18. 18.
    Rubin LA, Kurman CC, Fritz ME, Biddison WE, Boutin B, Yarchoan R, Nelson DL: Soluble interleukin 2 receptors are released from activated human lymphoid cells in vitro. J Immunol 135:3172–3177, 1985Google Scholar
  19. 19.
    Osawa H, Josimovic-Alasevic O, Diamatstein T: Interleukin 2 receptors are released by cells in vitro and in vivo. I. Detection of soluble IL2 receptors in cell culture supernatants and in the serum of mice by an immunoradiometric assay. Eur J Immunol 16:467–469, 1986Google Scholar
  20. 20.
    Rubin LA, Jay G, Nelson DL: The released interleukin-2 receptor binds interleukin-2 efficiently. J Immunol 137:3841–3844, 1986Google Scholar
  21. 21.
    Nelson DL, Rubin LA, Kurman CC, Fritz ME, Boutin B: An analysis of the cellular requirements for the production of soluble interleukin-2 receptors in vitro. J Clin Immunol 6:114–120, 1986Google Scholar
  22. 22.
    Pizzolo G, Chilosi M, Semenzato G: Annotation. The soluble interleukin-2 receptor in haematological disorders. Br J Haematol 67:377–380, 1987Google Scholar
  23. 23.
    Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ, Rothfield NF, Schaller JG, Talal N, Winchester RJ: The 1982 revised criteria for the classification of systemic lupus erythematosus. Arth Rheum 25:1271–1277, 1982Google Scholar
  24. 24.
    Ropes MV, Bennet GA, Cobb S, Jacox R, Jessar RA: 1958 revision of diagnostic criteria for rheumatoid arthritis. Bull Rheum Dis 9:175–176, 1958Google Scholar
  25. 25.
    Veyes EM, Hermanns P, Verbruggen G, Schindler J, Goldstein G: Evaluation of T cell subsets with monoclonal antibodies in synovial fluid in rheumatoid arthritis. J Rheumatol 9:821–826, 1982Google Scholar
  26. 26.
    Chilosi M, Semenzato G, Cetto G, Ambrosetti A, Fiore-Donati L, Perona G, Berton G, Lestani M, Scarpa A, Agostini C, Trentin L, Zambello R, Masciarelli M, Dazzi F, Caligaris-Cappio F, Pizzolo G: Soluble interleukin-2 receptors in the sera of patients with hairy cell leukemia: Relationship with the effect of recombinant alpha-interferon therapy on clinical parameters and natural killer in vitro activity. Blood 70:1530–1535, 1987Google Scholar
  27. 27.
    Balderas RS, Josimovic-Alasevic O, Diamatstein T, Dixon FJ. Theofilopoulos AN: Elevated titers of cell-free interleukin 2 receptor in serum of lupus mice. J Immunol 139:1496–1500, 1987Google Scholar
  28. 28.
    Katz P, Zaytonu A, Lee JA, Pannush RS, Longley S: Abnormal natural killer cell activity in systemic lupus erythematous: An intrinsic defect in the lytic event. J Immunol 129:1966–1971, 1982Google Scholar
  29. 29.
    Emery P, Panayi GS, Nouri AM: Interleukin-2 reverses deficient cell-mediated immune responses in rheumatoid arthritis. Clin Exp Immunol 57:123–129, 1984Google Scholar
  30. 30.
    Tsokos GC, Smith PL, Christian CB, Lipnick RL, Balow JE, Djeu JY: Interleukin-2 restores the depressed allogenic cell mediated lympholysis and natural killer cell activity in patients with systemic lupus erythematosus. Clin Immunol Immunopathol 34:379–386, 1985Google Scholar
  31. 31.
    Pizzolo G, Chilosi M, Vinante F, Dazzi F, Lestani M, Perona G, Benedetti F, Todeschini G, Vincenzi C, Trentin L, Semenzato G: Soluble interleukin-2 receptors in the serum of patients with Hodgkin's disease. Br J Cancer 55:427–428, 1987Google Scholar
  32. 32.
    Semenzato G, Foà R, Agostini C, Zambello R, Trentin L, Vinante F, Benedetti F, Chilosi M, Pizzolo G: High levels of soluble interleukin-2 receptor in patients with B chronic lymphocytic leukemia. Blood 70:396–400, 1987Google Scholar
  33. 33.
    Lawrence EC, Berger MB, Brousseau KP, Rodriquez TM, Siegel SJ, Kurman CC, Nelson DL: Elevated serum levels of soluble interleukin-2 receptors in active pulmonary sarcoidosis: Relative specificity and association with hypercalcemia. Sarcoidosis 4:87–93, 1987Google Scholar
  34. 34.
    Colvin RB, Fuller TC, MacKeen L, Kung PC, Ip SH, Cosimi AB: Plasma interleukin 2 receptor levels in renal allograft recipients. Clin Immunol Immunopathol 43:273–276, 1987Google Scholar
  35. 35.
    Alberti A, Chemello L, Fattovich G, Semenzato G, Vinante F, Pizzolo G: Soluble interleukin 2 receptors in serum of patients with acute and chronic viral hepatitis (submitted for publication).Google Scholar
  36. 36.
    Burmester GR, Jahn B, Gramatzki M, Zacker J, Kalden JR: Activated T cells in vivo and in vitro: Divergence in expression of Tac and Ia antigens in the nonblastoid small T cells of inflammation and normal T cells activated in vitro. J Immunol 133:1230–1234, 1984Google Scholar
  37. 37.
    Waalen K, Foore O, Linker-Israeli M, Thoen J: Evidence of an activated T-cell system with augmented turnover of interleukin 2 in rheumatoid arthritis. Stimulation of human T lymphocytes by dendritic cells as a model for rheumatoid T cell activation. Scand J Immunol 25:367–373, 1987Google Scholar
  38. 38.
    Damle NK, Childs AL, Doyle LV: Immunoregulatory T lymphocytes in man. Soluble antigen-specific suppressor-inducer T lymphocytes are derived from the CD4+CD45R-p80+ subpopulation. J Immunol 139:1501–1508, 1987Google Scholar
  39. 39.
    Goto M, Miyamoto T, Nishioka K, Uchida S: T cytotoxic and helper cells are markedly increased, and T suppressor and inducer cells are markedly decreased, in rheumatoid synovial fluids. Arthr Rheum 30:737–743, 1987Google Scholar
  40. 40.
    Pitzalis C, Kingsley G, Murphy J, Panayi G: Abnormal distribution of the helper-inducer T-lymphocyte subsets in the rheumatoid joints. Clin Immunol Immunopathol 45:252–258, 1987Google Scholar
  41. 41.
    Cupps TR, Fauci AS: Corticosteroid-mediated immunoregulation in man. Immunol Rev 65:133–155, 1982Google Scholar
  42. 42.
    Arya SK, Wong-Staal F, Gallo RC: Dexamethasone-mediated inhibition of human T cell growth factor and y-interferon messenger RNA. J Immunol 133:273–276, 1984Google Scholar

Copyright information

© Plenum Publishing Corporation 1988

Authors and Affiliations

  • G. Semenzato
    • 1
    • 2
  • L. M. Bambara
    • 1
    • 2
  • D. Biasi
    • 1
    • 2
  • A. Frigo
    • 1
    • 2
  • F. Vinante
    • 1
    • 2
  • B. Zuppini
    • 1
    • 2
  • L. Trentin
    • 1
    • 2
  • C. Feruglio
    • 1
    • 2
  • M. Chilosi
    • 1
    • 2
  • G. Pizzolo
    • 1
    • 2
  1. 1.Department of Clinical Medicine, First Medical Clinic and Clinical Immunology BranchPadua University School of MedicinePaduaItaly
  2. 2.Departments of Medical Pathology, Hematology, and PathologyVerona University School of MedicineVeronaItaly
  3. 3.Istituto di Medicina Clinica/Clinica Medica 1PadovaItaly

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