Tilbery, Charles P.; Felipe, Eduardo; Mota, Izabel Maria; Scheinberg, Morton A.

doi:10.1590/S0004-282X1994000200011

Resumos

Em 26 pacientes com diagnóstico definido de esclerose múltipla foram colhidas amostras de sangue e pesquisados os receptores solúveis de interleucina-2 (RsIL-2). Para tal os pacientes foram divididos em dois grupos: um constituído de 14 pacientes em surto da doença e o outro com 12 pacientes em remissão da moléstia. Além destes, procedeu-se a colheita de material para a mesma pesquisa em 8 pacientes com outras doenças neurológicas. Os resultados demonstraram aumento dos RsIL-2 em 50% dos casos do grupo de pacientes em surto da doença, fato não observado nos demais pacientes dos demais grupos. Estes resultados confirmam a hipótese da ativação de células Tem pacientes em surto de esclerose múltipla, corroborando a hipótese da existência de um desequilíbrio imunológico na doença.

esclerose múltipla; surto; interleucina-2 receptor solúvel

Serum samples were analysed for interleukin-2 receptors levels (sIL-2R) in 26 patients with definite multiple sclerosis as defined by Poser and col. Three groups of patients form the basis of this study: group I, with 14 patients with clinical evidence of active disease; group II, with 12 patients with clinically stable multiple sclerosis; and group III, with 8 patients with other neurological diseases. Blood was collected by venipuncture and centrifuged. All samples were stored at -20°C until testing. The assay used monoclonal antibodies against epitopes of interleukin-2 receptors. In the wells of a microtiter plate coated with anti-soluble interleukin-2 receptors (Immunotech SA) samples to be measured or standards are incubated in the presence of a second monoclonal antibody conjugated with alkaline phosphatase. The amount of bound enzyme-conjugate is measured by adding a chromogenic substrate. The intensity of the resulting colour is proportional to the sIL-2R concentration present in the sample. Increased serum levels of sIL-2R were found in 7 of 14 patients with active multiple sclerosis (50%), in only 1 of the 12 patients with clinically stable multiple sclerosis and in none of the patients with other neurological diseases.

multiple sclerosis; active disease; soluble interleukin-2 receptors

Aumento dos receptores solúveis da interleucina-2 na esclerose múltipla: estudo preliminar em 26 pacientes

Elevated levels of soluble interleukin-2 receptors in multiple sclerosis: preliminary report on 26 patients

Charles P. Tilbery^I; Eduardo Felipe^II; Izabel Maria Mota^III; Morton A. Scheinberg^IV

^IDisciplina de Neurologia da Faculdade de Ciências Médicas da Santa Casa de São Paulo e da Divisão de Imunologia do Instituto do Câncer Arnaldo Vieira de Carvalho e Instituto Brasileiro de Controle do Câncer: Professor Adjunto de Neurologia

^IIDisciplina de Neurologia da Faculdade de Ciências Médicas da Santa Casa de São Paulo e da Divisão de Imunologia do Instituto do Câncer Arnaldo Vieira de Carvalho e Instituto Brasileiro de Controle do Câncer: Professor Instrutor de Neurologia

^IIIDisciplina de Neurologia da Faculdade de Ciências Médicas da Santa Casa de São Paulo e da Divisão de Imunologia do Instituto do Câncer Arnaldo Vieira de Carvalho e Instituto Brasileiro de Controle do Câncer: Biomédica da Divisão de Imunologia

^IVDisciplina de Neurologia da Faculdade de Ciências Médicas da Santa Casa de São Paulo e da Divisão de Imunologia do Instituto do Câncer Arnaldo Vieira de Carvalho e Instituto Brasileiro de Controle do Câncer: Chefe da Divisão de Imunologia

RESUMO

Em 26 pacientes com diagnóstico definido de esclerose múltipla foram colhidas amostras de sangue e pesquisados os receptores solúveis de interleucina-2 (RsIL-2). Para tal os pacientes foram divididos em dois grupos: um constituído de 14 pacientes em surto da doença e o outro com 12 pacientes em remissão da moléstia. Além destes, procedeu-se a colheita de material para a mesma pesquisa em 8 pacientes com outras doenças neurológicas. Os resultados demonstraram aumento dos RsIL-2 em 50% dos casos do grupo de pacientes em surto da doença, fato não observado nos demais pacientes dos demais grupos. Estes resultados confirmam a hipótese da ativação de células Tem pacientes em surto de esclerose múltipla, corroborando a hipótese da existência de um desequilíbrio imunológico na doença.

Palavras-chave: esclerose múltipla, surto, interleucina-2 receptor solúvel.

SUMMARY

Serum samples were analysed for interleukin-2 receptors levels (sIL-2R) in 26 patients with definite multiple sclerosis as defined by Poser and col. Three groups of patients form the basis of this study: group I, with 14 patients with clinical evidence of active disease; group II, with 12 patients with clinically stable multiple sclerosis; and group III, with 8 patients with other neurological diseases. Blood was collected by venipuncture and centrifuged. All samples were stored at -20°C until testing. The assay used monoclonal antibodies against epitopes of interleukin-2 receptors. In the wells of a microtiter plate coated with anti-soluble interleukin-2 receptors (Immunotech SA) samples to be measured or standards are incubated in the presence of a second monoclonal antibody conjugated with alkaline phosphatase. The amount of bound enzyme-conjugate is measured by adding a chromogenic substrate. The intensity of the resulting colour is proportional to the sIL-2R concentration present in the sample. Increased serum levels of sIL-2R were found in 7 of 14 patients with active multiple sclerosis (50%), in only 1 of the 12 patients with clinically stable multiple sclerosis and in none of the patients with other neurological diseases.

Key words: multiple sclerosis, active disease, soluble interleukin-2 receptors.

Texto completo disponível apenas em PDF.

Full text available only in PDF format.

Aceite: 18-outubro-1993.

Estudo da Disciplina de Neurologia da Faculdade de Ciências Médicas da Santa Casa de São Paulo e da Divisão de Imunologia do Instituto do Câncer Arnaldo Vieira de Carvalho e Instituto Brasileiro de Controle do Câncer

Dr. Charles Peter Tilbery - Rua Sampaio Vidal 855 - 01443-001 São Paulo SP - Brasil.

1. Adachi K, Kumamoto T, Araki S. Interlucin-2 receptor levels indicating relapse in multiple sclerosis. Lancet 1989, 1:559-560.
2. Adachi K, Kumamoto T, Araki S. Elevated soluble interleukin-2 levels in patients with active multiple sclerosis. Ann Neurol 1990, 28:687-691.
3. Antel JP, Arnason BGW, Medof ME. Suppressor cell function in multiple sclerosis. Ann Neurol 1979, 5:338-342.
4. Bellamy AS, Calder VL, Feldman M, Davidson AN. The distribution of interleukin-2 receptor bearing lymphocytes in multiple sclerosis: evidence for a key role of activated lymphocytes. Clin Exp Immunol 1985, 61:248-256.
5. Capra R, Mattiolo F, Marciano N et al. Significantly higher levels of soluble interleukin-2 in patients with relapsing remitting multiple sclerosis compared with healthy subjects. Arch Neurol 1990, 47:254-259.
6. Gallo P, Piccino MG, Pagni S et al. Immune activation in multiple sclerosis: study of IL-2, sIL-2R and gama-IFN levels in serum and cerebrospinal fluid. J Neurol Sci 1989, 92:9-15.
7. Greenberg SJ, Marcon L, Hurwitz BJ, Nelson DL. Elevated levels of soluble interleukin-2 receptors in multiple sclerosis. N Engl J Med 1988,319:1019-1020.
8. Hafler DA, Weiner HL. In vivo labelling of blood T cells: rapid traffic into cerebrospinal fluid in multiple sclerosis. Ann Neurol 1987, 22:89-93.
9. Hartung HP, Hughes RA, Taylor et al. T cell activation in Guillain Barre syndrome and in MS: elevated serum levels of soluble IL-2 receptors. Neurology 1990, 40:215-218.
10. Hofman FM, von Hanwehr RI, Dinarello CA el al. Immunoregulatory molecules and IL-2 receptor identified in multiple sclerosis brain. J Immunol 1986, 136:3239-3245.
11. Manoussakis MN, Papadopoulos GK, Drosos A, Moutsopoulos HM. Soluble interleukin-2 receptor molecules in the serum of patients with autoimmune diseases. Clin Immunol Immunopath 1989, 50:321-332.
12. Merril JE, Mohlstrom C, Uittenboagaart C et al. Response to and production of interleukin-2 by peripheral blood and cerebrospinal fluid lymphocytes of patients with multiple sclerosis. J Immunol 1984, 133:1931-1937.
13. Morimoto C, Hafler DA, Weiner HL. Selective loss of the suppressor inducer T cell subset in progressive multiple sclerosis: analysis with anti-2 H4 monoclonal antibody. N Engl J Med 1987, 316:67-72.
14. Poser CM, Patty DW, Scheimberg L et al. New diagnostic criteria for multiple sclerosis: guidelines for research protocols. Ann Neurol 1983, 13:227-231.
15. Robb BR. Low and high affinity cellular receptors for interleukin-2: implications for the level of Tac antigen. J Exp Med 1987, 160:1126-1130.
16. Rubin LA. Soluble interleukin-2 receptores are realeased from activated human lymphoid cells in vitro. J Immunol 1985, 135:3172-3175.
17. Rudick RA, Barna BP. Serum interleukin-2 and soluble interleukin-2 receptor in patients with multiple sclerosis who are experiencing severe fatigue. Arch Neurol 1990, 47:254-255.
18. Scheimberg MA, Ikejiri M, Silva M, Mota M. Interleukin-2 receptor membrane bound and in soluble form in the acute untreated uveitis. J Rheumatol 1992, 19:1362-1363.
19. Tilbery CP, Camargo Lima JG, Scheimberg MA, Santos LMB, Yamada FT. Comportamento dos linfócitos T auxiliador e T supressor na esclerose múltipla: estudo preliminar. Rev Paul Med 1984, 102:181 -183.
20. Tilbery CP, Camargo Lima JG, Scheimberg MA. Aspectos imulogógicos na esclerose múltipla: subpopulacoes de linfócitos e anticorpos anti-linfocitários. Rev Paul Med 1987, 105:134-140.
21. Trotter JL, Clifford DB, Mclnnis JE et al. Correlation of immunological studies and disease progression in chronic progressive multiple sclerosis. Ann Neurol 1989, 25:172-178.
22. Vaisberg M, Scheimberg MA. Simultaneous evaluation of membrane bound and soluble interleukin receptor expression in the blood and synovial fluid of patients with rheumatoid arthritis. Clin Exp Rheumatol 1990, 8:579-584.

Datas de Publicação

Publicação nesta coleção
19 Jan 2011
Data do Fascículo
Jun 1994

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

[1] 1. Adachi K, Kumamoto T, Araki S. Interlucin-2 receptor levels indicating relapse in multiple sclerosis. Lancet 1989, 1:559-560.

[2] 2. Adachi K, Kumamoto T, Araki S. Elevated soluble interleukin-2 levels in patients with active multiple sclerosis. Ann Neurol 1990, 28:687-691.

[3] 3. Antel JP, Arnason BGW, Medof ME. Suppressor cell function in multiple sclerosis. Ann Neurol 1979, 5:338-342.

[4] 4. Bellamy AS, Calder VL, Feldman M, Davidson AN. The distribution of interleukin-2 receptor bearing lymphocytes in multiple sclerosis: evidence for a key role of activated lymphocytes. Clin Exp Immunol 1985, 61:248-256.

[5] 5. Capra R, Mattiolo F, Marciano N et al. Significantly higher levels of soluble interleukin-2 in patients with relapsing remitting multiple sclerosis compared with healthy subjects. Arch Neurol 1990, 47:254-259.

[6] 6. Gallo P, Piccino MG, Pagni S et al. Immune activation in multiple sclerosis: study of IL-2, sIL-2R and gama-IFN levels in serum and cerebrospinal fluid. J Neurol Sci 1989, 92:9-15.

[7] 7. Greenberg SJ, Marcon L, Hurwitz BJ, Nelson DL. Elevated levels of soluble interleukin-2 receptors in multiple sclerosis. N Engl J Med 1988,319:1019-1020.

[8] 8. Hafler DA, Weiner HL. In vivo labelling of blood T cells: rapid traffic into cerebrospinal fluid in multiple sclerosis. Ann Neurol 1987, 22:89-93.

[9] 9. Hartung HP, Hughes RA, Taylor et al. T cell activation in Guillain Barre syndrome and in MS: elevated serum levels of soluble IL-2 receptors. Neurology 1990, 40:215-218.

[10] 10. Hofman FM, von Hanwehr RI, Dinarello CA el al. Immunoregulatory molecules and IL-2 receptor identified in multiple sclerosis brain. J Immunol 1986, 136:3239-3245.

[11] 11. Manoussakis MN, Papadopoulos GK, Drosos A, Moutsopoulos HM. Soluble interleukin-2 receptor molecules in the serum of patients with autoimmune diseases. Clin Immunol Immunopath 1989, 50:321-332.

[12] 12. Merril JE, Mohlstrom C, Uittenboagaart C et al. Response to and production of interleukin-2 by peripheral blood and cerebrospinal fluid lymphocytes of patients with multiple sclerosis. J Immunol 1984, 133:1931-1937.

[13] 13. Morimoto C, Hafler DA, Weiner HL. Selective loss of the suppressor inducer T cell subset in progressive multiple sclerosis: analysis with anti-2 H4 monoclonal antibody. N Engl J Med 1987, 316:67-72.

[14] 14. Poser CM, Patty DW, Scheimberg L et al. New diagnostic criteria for multiple sclerosis: guidelines for research protocols. Ann Neurol 1983, 13:227-231.

[15] 15. Robb BR. Low and high affinity cellular receptors for interleukin-2: implications for the level of Tac antigen. J Exp Med 1987, 160:1126-1130.

[16] 16. Rubin LA. Soluble interleukin-2 receptores are realeased from activated human lymphoid cells in vitro. J Immunol 1985, 135:3172-3175.

[17] 17. Rudick RA, Barna BP. Serum interleukin-2 and soluble interleukin-2 receptor in patients with multiple sclerosis who are experiencing severe fatigue. Arch Neurol 1990, 47:254-255.

[18] 18. Scheimberg MA, Ikejiri M, Silva M, Mota M. Interleukin-2 receptor membrane bound and in soluble form in the acute untreated uveitis. J Rheumatol 1992, 19:1362-1363.

[19] 19. Tilbery CP, Camargo Lima JG, Scheimberg MA, Santos LMB, Yamada FT. Comportamento dos linfócitos T auxiliador e T supressor na esclerose múltipla: estudo preliminar. Rev Paul Med 1984, 102:181 -183.

[20] 20. Tilbery CP, Camargo Lima JG, Scheimberg MA. Aspectos imulogógicos na esclerose múltipla: subpopulacoes de linfócitos e anticorpos anti-linfocitários. Rev Paul Med 1987, 105:134-140.

[21] 21. Trotter JL, Clifford DB, Mclnnis JE et al. Correlation of immunological studies and disease progression in chronic progressive multiple sclerosis. Ann Neurol 1989, 25:172-178.

[22] 22. Vaisberg M, Scheimberg MA. Simultaneous evaluation of membrane bound and soluble interleukin receptor expression in the blood and synovial fluid of patients with rheumatoid arthritis. Clin Exp Rheumatol 1990, 8:579-584.