Skip to main content
PMC home page
Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1993 Jul;93(1):39–44. doi: 10.1111/j.1365-2249.1993.tb06494.x

B cell activation in clinically quiescent systemic lupus erythematosus (SLE) is related to immunoglobulin levels, but not to levels of anti-dsDNA, nor to concurrent T cell activation.

P E Spronk 1, B T vd Gun 1, P C Limburg 1, C G Kallenberg 1
PMCID: PMC1554751  PMID: 8100746

Abstract

In clinically quiescent SLE hypergammaglobulinaemia, presence of autoantibodies, and increased soluble IL-2 receptors (sIL-2R) have been reported, suggesting persistent B as well as T cell activation. In contrast, the primary immune response to test antigens is markedly decreased. To analyse these phenomena at a cellular level, we undertook a cross-sectional study on 13 non-active SLE patients and 15 controls. We determined the composition of lymphocyte subsets with special attention to activation markers (CD25, HLA-DR, CD38) and the presence of naive T cells (CD45RO-), and related those findings to serological parameters. In non-active SLE patients the expression of activation markers on B cells and T cells was higher than in normal controls (P < or = 0.02), but was not interrelated. Percentages of activated B cells in SLE were related to levels of total IgG (P < 0.02) and IgM (P < 0.02) but not to anti-dsDNA, suggesting a disordered immune system also in clinically quiescent SLE. Numbers of CD4+ cells (P < 0.001) and CD4+CD45RO- cells (P < 0.05) were decreased. The latter finding might explain the anergy to primary test antigens in clinically quiescent SLE.

Full text

PDF
42

Selected References

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

  1. Bombardier C., Gladman D. D., Urowitz M. B., Caron D., Chang C. H. Derivation of the SLEDAI. A disease activity index for lupus patients. The Committee on Prognosis Studies in SLE. Arthritis Rheum. 1992 Jun;35(6):630–640. doi: 10.1002/art.1780350606. [DOI] [PubMed] [Google Scholar]
  2. Brozek C. M., Hoffman C. L., Savage S. M., Searles R. P. Systemic lupus erythematosus sera inhibit antigen presentation by macrophages to T cells. Clin Immunol Immunopathol. 1988 Feb;46(2):299–313. doi: 10.1016/0090-1229(88)90192-4. [DOI] [PubMed] [Google Scholar]
  3. Donati D., Degiannis D., Homer L., Gastaldi L., Raskova J., Raska K., Jr Immune deficiency in uremia: interleukin-2 production and responsiveness and interleukin-2 receptor expression and release. Nephron. 1991;58(3):268–275. doi: 10.1159/000186435. [DOI] [PubMed] [Google Scholar]
  4. Eisenberg R. A., Dyer K., Craven S. Y., Fuller C. R., Yount W. J. Subclass restriction and polyclonality of the systemic lupus erythematosus marker antibody anti-Sm. J Clin Invest. 1985 Apr;75(4):1270–1277. doi: 10.1172/JCI111826. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Gorla R., Airò P., Franceschini F., Stefani E., Braga S., Tincani A., Cattaneo R. Decreased number of peripheral blood CD4 + CD29+ lymphocytes and increased in vitro spontaneous production of anti-DNA antibodies in patients with active systemic lupus erythematosus. J Rheumatol. 1990 Aug;17(8):1048–1053. [PubMed] [Google Scholar]
  6. Kallenberg C. G., Limburg P. C., Van Slochteren C., Van der Woude F. J., The T. H. B cell activity in systemic lupus erythematosus: depressed in vivo humoral immune response to a primary antigen (haemocyanin) and increased in vitro spontaneous immunoglobulin synthesis. Clin Exp Immunol. 1983 Aug;53(2):371–383. [PMC free article] [PubMed] [Google Scholar]
  7. Kallenberg C. G., van Dissel-Emiliani F., Huitema M. G., Limburg P. C., The T. H. B-cell proliferation and differentiation in systemic lupus erythematosus and mixed connective tissue disease. J Clin Lab Immunol. 1988 Jun;26(2):55–61. [PubMed] [Google Scholar]
  8. Kimura M., Gleichmann E. Depressed antibody responses to exogenous antigens in mice with lupus-like graft-versus-host disease. Clin Immunol Immunopathol. 1987 Apr;43(1):97–109. doi: 10.1016/0090-1229(87)90161-9. [DOI] [PubMed] [Google Scholar]
  9. Linker-Israeli M., Quismorio F. P., Jr, Horwitz D. A. CD8+ lymphocytes from patients with systemic lupus erythematosus sustain, rather than suppress, spontaneous polyclonal IgG production and synergize with CD4+ cells to support autoantibody synthesis. Arthritis Rheum. 1990 Aug;33(8):1216–1225. doi: 10.1002/art.1780330823. [DOI] [PubMed] [Google Scholar]
  10. Lévi F. A., Canon C., Touitou Y., Sulon J., Mechkouri M., Ponsart E. D., Touboul J. P., Vannetzel J. M., Mowzowicz I., Reinberg A. Circadian rhythms in circulating T lymphocyte subtypes and plasma testosterone, total and free cortisol in five healthy men. Clin Exp Immunol. 1988 Feb;71(2):329–335. [PMC free article] [PubMed] [Google Scholar]
  11. McInerney M. F., Clough J. D., Senitzer D., Cathcart M. K. Two distinct subsets of patients with systemic lupus erythematosus. Clin Immunol Immunopathol. 1988 Oct;49(1):116–132. doi: 10.1016/0090-1229(88)90101-8. [DOI] [PubMed] [Google Scholar]
  12. Merkenschlager M., Terry L., Edwards R., Beverley P. C. Limiting dilution analysis of proliferative responses in human lymphocyte populations defined by the monoclonal antibody UCHL1: implications for differential CD45 expression in T cell memory formation. Eur J Immunol. 1988 Nov;18(11):1653–1661. doi: 10.1002/eji.1830181102. [DOI] [PubMed] [Google Scholar]
  13. Mimura T., Fernsten P., Jarjour W., Winfield J. B. Autoantibodies specific for different isoforms of CD45 in systemic lupus erythematosus. J Exp Med. 1990 Aug 1;172(2):653–656. doi: 10.1084/jem.172.2.653. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Morimoto C., Steinberg A. D., Letvin N. L., Hagan M., Takeuchi T., Daley J., Levine H., Schlossman S. F. A defect of immunoregulatory T cell subsets in systemic lupus erythematosus patients demonstrated with anti-2H4 antibody. J Clin Invest. 1987 Mar;79(3):762–768. doi: 10.1172/JCI112882. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Munves E. F., Schur P. H. Antibodies to Sm and RNP. Prognosticators of disease involvement. Arthritis Rheum. 1983 Jul;26(7):848–853. doi: 10.1002/art.1780260705. [DOI] [PubMed] [Google Scholar]
  16. Murakami M., Kumagai S., Sugita M., Iwai K., Imura H. In vitro induction of IgG anti-DNA antibody from high density B cells of systemic lupus erythematosus patients by an HLA DR-restricted T cell clone. Clin Exp Immunol. 1992 Nov;90(2):245–250. doi: 10.1111/j.1365-2249.1992.tb07936.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Rubin L. A., Kurman C. C., Fritz M. E., Biddison W. E., Boutin B., Yarchoan R., Nelson D. L. Soluble interleukin 2 receptors are released from activated human lymphoid cells in vitro. J Immunol. 1985 Nov;135(5):3172–3177. [PubMed] [Google Scholar]
  18. Sato K., Miyasaka N., Yamaoka K., Okuda M., Yata J., Nishioka K. Quantitative defect of CD4+2H4+ cells in systemic lupus erythematosus and Sjögren's syndrome. Arthritis Rheum. 1987 Dec;30(12):1407–1411. doi: 10.1002/art.1780301212. [DOI] [PubMed] [Google Scholar]
  19. Sawada S., Sugai S., Iijima S., Takei M., Paredes E., Hayama T., Nishinarita S., Hosokawa Y., Horie T., Obara T. Increased soluble CD4 and decreased soluble CD8 molecules in patients with Sjögren's syndrome. Am J Med. 1992 Feb;92(2):134–140. doi: 10.1016/0002-9343(92)90103-i. [DOI] [PubMed] [Google Scholar]
  20. Spronk P. E., ter Borg E. J., Limburg P. C., Kallenberg C. G. Plasma concentration of IL-6 in systemic lupus erythematosus; an indicator of disease activity? Clin Exp Immunol. 1992 Oct;90(1):106–110. doi: 10.1111/j.1365-2249.1992.tb05840.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Tan E. M. Antinuclear antibodies: diagnostic markers for autoimmune diseases and probes for cell biology. Adv Immunol. 1989;44:93–151. doi: 10.1016/s0065-2776(08)60641-0. [DOI] [PubMed] [Google Scholar]
  22. Tan E. M., Cohen A. S., Fries J. F., Masi A. T., McShane D. J., Rothfield N. F., Schaller J. G., Talal N., Winchester R. J. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1982 Nov;25(11):1271–1277. doi: 10.1002/art.1780251101. [DOI] [PubMed] [Google Scholar]
  23. Tanaka S., Matsuyama T., Steinberg A. D., Schlossman S. F., Morimoto C. Antilymphocyte antibodies against CD4+2H4+ cell populations in patients with systemic lupus erythematosus. Arthritis Rheum. 1989 Apr;32(4):398–405. doi: 10.1002/anr.1780320408. [DOI] [PubMed] [Google Scholar]
  24. Ting C. K., Hsieh K. H. A long-term immunological study of childhood onset systemic lupus erythematosus. Ann Rheum Dis. 1992 Jan;51(1):45–51. doi: 10.1136/ard.51.1.45. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Tomkinson B. E., Brown M. C., Ip S. H., Carrabis S., Sullivan J. L. Soluble CD8 during T cell activation. J Immunol. 1989 Apr 1;142(7):2230–2236. [PubMed] [Google Scholar]
  26. Winfield J. B., Shaw M., Yamada A., Minota S. Subset specificity of antilymhocyte antibodies in systemic lupus erythematosus. II. Preferential reactivity with T4 + cells is associated with relative depletion of autologous T4 + cells. Arthritis Rheum. 1987 Feb;30(2):162–168. doi: 10.1002/art.1780300206. [DOI] [PubMed] [Google Scholar]
  27. ter Borg E. J., Horst G., Hummel E., Limburg P. C., Kallenberg C. G. Rises in anti-double stranded DNA antibody levels prior to exacerbations of systemic lupus erythematosus are not merely due to polyclonal B cell activation. Clin Immunol Immunopathol. 1991 Apr;59(1):117–128. doi: 10.1016/0090-1229(91)90086-p. [DOI] [PubMed] [Google Scholar]

Articles from Clinical and Experimental Immunology are provided here courtesy of British Society for Immunology

RESOURCES