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. 1990 Jul;49(7):507–511. doi: 10.1136/ard.49.7.507

Analysis of impaired in vitro immunoglobulin synthesis in rheumatoid arthritis.

I Jokinen 1, K Poikonen 1, T Möttönen 1, P Hannonen 1, M Oka 1, J Ilonen 1, H M Surcel 1, R Karttunen 1, H Arvilommi 1
PMCID: PMC1004138  PMID: 2143370

Abstract

Decreased immunoglobulin production in pokeweed mitogen driven lymphocyte cultures has been reported in rheumatoid arthritis (RA). Here various activators and experimental designs have been used to determine the contribution of B cells, T cells, or monocytes to this low response. Sixty patients with RA and paired controls were studied at the onset of disease and again six months later. Concentrations of IgA, IgG, and IgM in cultures of RA peripheral blood mononuclear cells stimulated with thymus dependent activators were already decreased at the onset of the disease. Six months later RA mononuclear cells produced even lower concentrations of immunoglobulin. In contrast, stimulation with a T cell independent activator showed that RA B lymphocytes had retained normal potential to synthesise immunoglobulin. Poor helper function was indicated by costimulation experiments and cultures of mixed mononuclear cells from patients and controls. This notion was supported also by the fact that phytohaemagglutinin induced interleukin-2 production by RA mononuclear cells was less than half of the control values. Nonspecific suppressor activity was similar in RA and controls. Monocyte functions were normal when tested by addition of indomethacin or 2-mercaptoethanol to the mitogen activated cultures. The defect in mitogen stimulated immunoglobulin production in vitro of RA mononuclear cells thus was more pronounced with time and probably reflects impaired mediator associated help in the differentiation of B lymphocytes into immunoglobulin secreting cells.

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Selected References

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

  1. Boling E. P., Ohishi T., Wahl S. M., Misiti J., Wistar R., Jr, Wilder R. L. Humoral immune function in severe, active rheumatoid arthritis. Clin Immunol Immunopathol. 1987 May;43(2):185–194. doi: 10.1016/0090-1229(87)90126-7. [DOI] [PubMed] [Google Scholar]
  2. Ceuppens J. L., Goodwin J. S. Endogenous prostaglandin E2 enhances polyclonal immunoglobulin production by tonically inhibiting T suppressor cell activity. Cell Immunol. 1982 Jun;70(1):41–54. doi: 10.1016/0008-8749(82)90131-9. [DOI] [PubMed] [Google Scholar]
  3. Combe B., Pope R. M., 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. 1985 Mar;59(3):520–528. [PMC free article] [PubMed] [Google Scholar]
  4. Emery P., Gentry K. C., Mackay I. R., Muirden K. D., Rowley M. Deficiency of the suppressor inducer subset of T lymphocytes in rheumatoid arthritis. Arthritis Rheum. 1987 Aug;30(8):849–856. doi: 10.1002/art.1780300802. [DOI] [PubMed] [Google Scholar]
  5. Fauci A. S., Pratt K. R., Whalen G. Activation of human B lymphocytes. IV. Regulatory effects of corticosteroids on the triggering signal in the plaque-forming cell response of human peripheral blood B lymphocytes to polyclonal activation. J Immunol. 1977 Aug;119(2):598–603. [PubMed] [Google Scholar]
  6. Forsgren A., Svedjelund A., Wigzell H. Lymphocyte stimulation by protein A of Staphylococcus aureus. Eur J Immunol. 1976 Mar;6(3):207–213. doi: 10.1002/eji.1830060312. [DOI] [PubMed] [Google Scholar]
  7. Gillis S., Ferm M. M., Ou W., Smith K. A. T cell growth factor: parameters of production and a quantitative microassay for activity. J Immunol. 1978 Jun;120(6):2027–2032. [PubMed] [Google Scholar]
  8. Haynes B. F., Fauci A. S. Activation of human B lymphocytes. III. Concanavalin A-induced generation of suppressor cells of the plaque-forming cell response of normal human B lymphocytes. J Immunol. 1977 Jun;118(6):2281–2287. [PubMed] [Google Scholar]
  9. Haynes B. F., Fauci A. S. Mechanisms of corticosteroid action on lymphocyte subpopulations. IV. Effects of in vitro hydrocortisone on naturally occuring and mitogen-induced suppressor cells in man. Cell Immunol. 1979 Apr;44(1):157–168. doi: 10.1016/0008-8749(79)90036-4. [DOI] [PubMed] [Google Scholar]
  10. Heilmann C., Petersen J. Secretion of immunoglobulins and IgM rheumatoid factor by pokeweed mitogen-induced blood lymphocytes: an evaluation by plaque forming cell assays. Acta Pathol Microbiol Immunol Scand C. 1984 Dec;92(6):371–376. doi: 10.1111/j.1699-0463.1984.tb00102.x. [DOI] [PubMed] [Google Scholar]
  11. Jelinek D. F., Lipsky P. E. Regulation of human B lymphocyte activation, proliferation, and differentiation. Adv Immunol. 1987;40:1–59. doi: 10.1016/s0065-2776(08)60237-0. [DOI] [PubMed] [Google Scholar]
  12. Jones B. M. Clinical evaluation of B cell and T-regulator cell function using a protein A haemolytic plaque assay. Clin Exp Immunol. 1981 Oct;46(1):196–205. [PMC free article] [PubMed] [Google Scholar]
  13. Jones B. M., Teng C. S., Yeung R. T. Evaluation of B-cell, T-helper-cell, and T-suppressor-cell function in patients with Graves' disease before and after treatment with anti-thyroid drugs. Clin Immunol Immunopathol. 1982 Nov;25(2):232–242. doi: 10.1016/0090-1229(82)90186-6. [DOI] [PubMed] [Google Scholar]
  14. Karttunen R., Nurmi T., Ilonen J., Surcel H. M. Cell-mediated immunodeficiency in Down's syndrome: normal IL-2 production but inverted ratio of T cell subsets. Clin Exp Immunol. 1984 Feb;55(2):257–263. [PMC free article] [PubMed] [Google Scholar]
  15. Kitas G. D., Salmon M., Farr M., Gaston J. S., Bacon P. A. Deficient interleukin 2 production in rheumatoid arthritis: association with active disease and systemic complications. Clin Exp Immunol. 1988 Aug;73(2):242–249. [PMC free article] [PubMed] [Google Scholar]
  16. Lasky H. P., Bauer K., Pope R. M. Increased helper inducer and decreased suppressor inducer phenotypes in the rheumatoid joint. Arthritis Rheum. 1988 Jan;31(1):52–59. doi: 10.1002/art.1780310108. [DOI] [PubMed] [Google Scholar]
  17. McKeown M. J., Hall N. D., Corvalan J. R. Defective monocyte accessory function due to surface sulphydryl (SH) oxidation in rheumatoid arthritis. Clin Exp Immunol. 1984 Jun;56(3):607–613. [PMC free article] [PubMed] [Google Scholar]
  18. Moretta A. Frequency and surface phenotype of human T lymphocytes producing interleukin 2. Analysis by limiting dilution and cell cloning. Eur J Immunol. 1985 Feb;15(2):148–155. doi: 10.1002/eji.1830150208. [DOI] [PubMed] [Google Scholar]
  19. Morimoto C., Letvin N. L., Boyd A. W., Hagan M., Brown H. M., Kornacki M. M., Schlossman S. F. The isolation and characterization of the human helper inducer T cell subset. J Immunol. 1985 Jun;134(6):3762–3769. [PubMed] [Google Scholar]
  20. Morimoto C., Letvin N. L., Distaso J. A., Aldrich W. R., Schlossman S. F. The isolation and characterization of the human suppressor inducer T cell subset. J Immunol. 1985 Mar;134(3):1508–1515. [PubMed] [Google Scholar]
  21. Paavonen T. Glucocorticoids enhance the in vitro Ig synthesis of pokeweed mitogen-stimulated human B cells by inhibiting the suppressive effect of T8+ T cells. Scand J Immunol. 1985 Jan;21(1):63–71. doi: 10.1111/j.1365-3083.1985.tb01404.x. [DOI] [PubMed] [Google Scholar]
  22. Panush R. S., Katz P., Longley S. In vitro immunoglobulin production by mononuclear cells in rheumatoid arthritis. Clin Immunol Immunopathol. 1983 Aug;28(2):252–264. doi: 10.1016/0090-1229(83)90159-9. [DOI] [PubMed] [Google Scholar]
  23. Pardo I., Carafa C., Dziarski R., Levinson A. I. Analysis of in vitro polyclonal B cell differentiation responses to bacterial peptidoglycan and pokeweed mitogen in rheumatoid arthritis. Clin Exp Immunol. 1984 May;56(2):253–262. [PMC free article] [PubMed] [Google Scholar]
  24. Poikonen K., Oka M., Möttönen T., Jokinen I., Arvilommi H. Synthesis of IgM, IgG and IgA in rheumatoid arthritis. Ann Rheum Dis. 1982 Dec;41(6):607–611. doi: 10.1136/ard.41.6.607. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Pryjma J., Muñoz J., Galbraith R. M., Fudenberg H. H., Virella G. Induction and suppression of immunoglobulin synthesis in cultures of human lymphocytes: effects of pokeweed mitogen and Staphylococcus aureus Cowan I. J Immunol. 1980 Feb;124(2):656–661. [PubMed] [Google Scholar]
  26. Pryjma J., Pituch-Noworolska A., Flad H. D., Ulmer A. J., Ernst M. Suppression of Staphylococcus aureus Cowan I-induced immunoglobulin synthesis in vitro: discrimination between the presence of suppressor T cell precursors and effectors. Clin Exp Immunol. 1986 Nov;66(2):348–357. [PMC free article] [PubMed] [Google Scholar]
  27. Rosenberg S. A., Lipsky P. E. Monocyte dependence of pokeweed mitogen-induced differentiation of immunoglobulin-secreting cells from human peripheral blood mononuclear cells. J Immunol. 1979 Mar;122(3):926–931. [PubMed] [Google Scholar]
  28. Salmon M., Kitas G. D., Gaston J. S., Bacon P. A. Interleukin-2 production and response by helper T-cell subsets in man. Immunology. 1988 Sep;65(1):81–85. [PMC free article] [PubMed] [Google Scholar]
  29. Segond P., Delfraissy J. F., Galanaud P., Wallon C., Massias P., Dormont J. Depressed primary in vitro antibody response in rheumatoid arthritis. Clin Exp Immunol. 1979 Aug;37(2):196–204. [PMC free article] [PubMed] [Google Scholar]
  30. Waalen K., Førre 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. 1987 Apr;25(4):367–373. doi: 10.1111/j.1365-3083.1987.tb02202.x. [DOI] [PubMed] [Google Scholar]
  31. Waldmann T. A., Broder S. Polyclonal B-cell activators in the study of the regulation of immunoglobulin synthesis in the human system. Adv Immunol. 1982;32:1–63. doi: 10.1016/s0065-2776(08)60720-8. [DOI] [PubMed] [Google Scholar]
  32. Warrington R. J. Interleukin-2 abnormalities in systemic lupus erythematosus and rheumatoid arthritis. A role for overproduction of interleukin-2 in human autoimmunity? J Rheumatol. 1988 Apr;15(4):616–620. [PubMed] [Google Scholar]
  33. Wolf R. E., Hall V. C. Interleukin-2 production and effect of thymosin fraction 5 on interleukin-2 production in rheumatoid arthritis. J Rheumatol. 1987 Oct;14(5):898–901. [PubMed] [Google Scholar]

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