Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Systemic lupus erythematosus—2005 annus mirabilis?

Nature Clinical Practice Rheumatology volume 2, pages 145–152 (2006)Cite this article

Abstract

We are about to enter a new era in the treatment of patients with systemic lupus erythematosus (SLE). For the past 40 years hydroxychloroquine sulfate and corticosteroids, together with varying combinations of immunosuppressive drugs, have been the main treatments for SLE. Although effective for many patients, some patients fail to respond to these drugs and even more suffer from major side effects due to the generalized nature of the immunosuppression. In this article we review the remarkable confluence of new therapies ranging from newer immunosuppressive drugs with fewer side effects, such as mycophenolate mofetil, to the more targeted approaches offered by biological agents. These agents have been designed to block molecules such as CD20, CD22 and interleukin-10 that are thought to have an integral part in the development of SLE. This wolf might not yet be about to become extinct but its survival is increasingly under threat!

Key Points

  • The current treatments for of systemic lupus erythematosus (SLE) are unsatisfactory

  • Hydroxychloroquine sulfate still has a place in the management of SLE because of its low record of toxicity and its potential role in lowering cholesterol

  • Mycophenolate mofetil is equally effective and better tolerated than cyclophosphamide at inducing SLE remission and as good as azathioprine at maintaining remission

  • B-cell depletion using a combination of cyclophosphamide, steroids and rituximab looks promising for reducing clinical features of SLE, but these results need to be confirmed in double-blind controlled trials

  • Anticytokine therapies and antagonists of the B-lymphocyte stimulating protein have shown promise in early therapeutic studies

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Interactions between T cells and antigen-presenting cells.
Figure 2: Interactions between T cells and B cells.

Similar content being viewed by others

References

  1. Merrill M and Shulman LE (1955) Determination of prognosis in chronic disease, illustrated by systemic lupus erythematosus. J Chron Dis 1: 12–32

    Article  Google Scholar 

  2. Gladman DD and Urowitz MB (2001) Prognosis, mortality and morbidity in systemic lupus erythematosus. In Dubois Lupus Erythematosus, edn 6, 54–56. (Eds Wallace D, Hahn BH) Philadelphia: Lippincott, Williams, Wilkins

    Google Scholar 

  3. Johnson AE et al. (1995) The prevalence and incidence of systemic lupus erythematosus (SLE) in Birmingham UK related to ethnicity and county of birth. Arthritis Rheum 38: 551–558

    Article  CAS  Google Scholar 

  4. Ramsey-Goldman R and Isenberg DA (2003) Systemic lupus erythematosus measures. Arthritis Care Res 49: S225–S233

    Article  Google Scholar 

  5. Mullins JF et al. (1956) Plaquenil in the treatment of lupus erythematosus. JAMA 161: 879–881

    Article  CAS  Google Scholar 

  6. Hodis HN et al. (1993) The lipid, lipoprotein and apolipoprotein effects of hydroxychloroquine in patients with systemic lupus erythematosus. J Rheumatol 20: 661–665

    CAS  PubMed  Google Scholar 

  7. Manzi S et al. (1997) Age specific incidence rate of myocardial infarction and angina in women with systemic lupus erythematosus: comparison with the Framingham Study. Am J Epidemiol 145: 408–415

    Article  CAS  Google Scholar 

  8. Fessler BJ et al. (2005) Systemic lupus erythematosus in three ethnic groups: XVI. Association of hydroxychloroquine use with reduced risk of damage accrual. Arthritis Rheum 52: 1473–1480

    Article  Google Scholar 

  9. Fulton B and Markham A (1996) Mycophenolate mofetil. A review of its pharmacodynamic and pharmacokinetic properties and clinical efficacy in renal transplantation. Drugs 51: 278–298

    Article  CAS  Google Scholar 

  10. Chan TM et al. (2000) Efficacy of mycophenolate mofetil in patients with diffuse proliferative lupus nephritis. N Engl J Med 343: 1156–1162

    Article  CAS  Google Scholar 

  11. Contreras G et al. (2004) Sequential therapies for proliferative lupus nephritis. N Engl J Med 350: 971–978

    Article  CAS  Google Scholar 

  12. Chan TM et al. (2005) Long term study of mycophenolate mofetil as continuous induction and maintenance treatment for diffuse proliferative nephritis. J Am Soc Nephrol 16: 1076–1082

    Article  CAS  Google Scholar 

  13. Boumpas DT et al. (1999) A pilot study of low dose fludarabine in membrane nephrotherapy to therapy. Clin Nephrol 52: 67–75

    CAS  PubMed  Google Scholar 

  14. Davis JC Jr et al. (1993) A pilot study of 2-chloro-2' deoxyadenosine in the treatment of glomerulonephritis in patients with systemic lupus erythematosus. Arthritis Rheum 41: 335–343

    Article  Google Scholar 

  15. Tahir H and Isenberg DA (2005) Novel therapies in lupus nephritis. Lupus 14: 77–82

    Article  CAS  Google Scholar 

  16. Mason LJ and Isenberg DA (2005) The pathogenesis of systemic lupus erythematosus, edn 3. In Oxford Textbook of Clinical Nephrology, 809–824 (Eds Davison AM et al.) Oxford: Oxford University Press

    Google Scholar 

  17. Edwards JC and Cambridge G (2001) Sustained improvement in rheumatoid arthritis following a protocol designed to deplete B lymphocytes. Rheumatology 40: 205–211

    Article  CAS  Google Scholar 

  18. Edwards JC et al. (2004) Efficacy of B cell targeted therapy with rituximab in patients with rheumatoid arthritis. N Engl J Med 350: 2572–2581

    Article  CAS  Google Scholar 

  19. Leandro MJ et al. (2002) An open study of B lymphocyte depletion in systemic lupus erythematosus. Arthritis Rheum 46: 2673–2677

    Article  Google Scholar 

  20. Leandro MJ et al. (2005) B-cell depletion in the treatment of patients with systemic lupus erythematosus: a longitudinal analysis of 24 patients. Rheumatology 44: 1542–1545

    Article  CAS  Google Scholar 

  21. Looney RJ et al. (2004) B lymphocytes in systemic lupus erythematosus; lessons from therapy targeting B cells. Lupus 13: 381–390

    Article  CAS  Google Scholar 

  22. Sfikakis PP et al. (2005) Remission of proliferative lupus nephritis following B cell depletion therapy is preceded by down-regulation of the T cell costimulatory molecule CD40 ligand: an open-label trial. Arthritis Rheum 52: 501–513

    Article  CAS  Google Scholar 

  23. Alarcon-Segovia D et al. (2003) LJP 394 for the prevention of renal flare in patients with systemic lupus erythematosus: results from a randomised double-blind placebo-controlled study. Arthritis Rheum 48: 442–454

    Article  CAS  Google Scholar 

  24. Weisman MH et al. (1997) Reduction in circulating dsDNA antibody titer after administration of LJP 394. J Rheumatol 24: 314–318

    CAS  PubMed  Google Scholar 

  25. Linnik MD et al. (2005) Relationship between anti-double stranded DNA antibodies and exacerbation of renal disease in patients with systemic lupus erythematosus. Arthritis Rheum 52: 1129–1137

    Article  CAS  Google Scholar 

  26. Lu L et al. (1999) Major peptide auto-epitopes for nucleosome specific T cells of human lupus. J Clin Invest 104: 345–355

    Article  CAS  Google Scholar 

  27. Wallace DJ (2002) Management of lupus erythematosus: recent insights. Curr Op in Rheumatol 14: 212–219

    Article  CAS  Google Scholar 

  28. Davidson A et al. (2005) Block and tackle: CTLA4Ig takes on lupus. Lupus 14: 197–203

    Article  CAS  Google Scholar 

  29. Finck BK et al. (1994) Treatment of murine lupus with CTLA4Ig. Science 265: 1225–1227

    Article  CAS  Google Scholar 

  30. Llorente L et al. (2000) Clinical and biologic effects of anti-interleukin 10 monoclonal antibody administration in systemic lupus erythematosus. Arthritis Rheum 43: 1790–1800

    Article  CAS  Google Scholar 

  31. Ehrenstein MR and Isenberg DA. Systemic lupus erythematosus—clinical features and aetiopathogenesis. In Oxford Textbook of Rheumatology ed 3, 819–842 (Eds Isenberg DA et al.) Oxford: Oxford University Press

  32. Breedveld FC and Keystone EC (2004) Immunosuppressive and other drugs–monotherapy versus combination therapy. In Oxford Textbook of Rheumatology 3rd edn, 458–465 9 (Eds Isenberg DA et al.). Oxford: Oxford University Press

    Google Scholar 

  33. Charles PJ et al. (2000) Assessment of antibodies to double-stranded DNA induced in rheumatoid arthritis patients following treatment with infliximab, a monoclonal antibody to tumor necrosis factor alpha: findings in open-label and randomised placebo controlled trials. Arthritis Rheum 43: 2383–2390

    Article  CAS  Google Scholar 

  34. Aringer M et al. (2004) Safety and efficacy of tumour necrosis factor alpha blockade in systemic lupus erythematosus: an open label study. Arthritis Rheum 50: 3161–3169

    Article  CAS  Google Scholar 

  35. Ronnblom L and Alm GV (2003) Systemic lupus erythematosus and the Type I interferon system. Arthritis Res Ther 5: 68–75

    Article  Google Scholar 

  36. Santiago-Raber ML et al. (2003) Type I interferon receptor deficiency reduces lupus like disease in NZB mice. J Exp Med 197: 777–788

    Article  CAS  Google Scholar 

  37. Merrill J (2005) BLyS antagonists and peptide tolerance induction. Lupus 14: 204–209

    Article  CAS  Google Scholar 

  38. Baker KP et al. (2003) Generation and characterization of LymphoStat-B, a human monoclonal antibody that antagonizes the bioactivities of B lymphocyte stimulator. Arthritis Rheum 48: 3253–3265

    Article  CAS  Google Scholar 

  39. Stohl W (2004) A therapeutic role for BLyS antagonists. Lupus 13: 317–322

    Article  CAS  Google Scholar 

  40. Schur P and Klickstein L (2002) Complement and systemic lupus erythematosus. In Dubois Lupus Erythematosus, edn 6, 243–259 (Eds Wallace DJ and Hahn BH) Philadelphia: Lippincott Williams & Wilkins

    Google Scholar 

  41. Davies KA et al. (1994) Complement deficiency and immune complex disease. Springer Semin Immunopathol 15: 397–416

    Article  CAS  Google Scholar 

  42. Rother RP et al. (2004) Inhibition of terminal complement: a novel therapeutic approach for the treatment of systemic lupus erythematosus. Lupus 13: 328–334

    Article  CAS  Google Scholar 

  43. Van Vollenhoven RF (2002) Dehydroepiandrosterone for the treatment of systemic lupus erythematosus. Expert Opin Pharmacother 3: 23–31

    Article  CAS  Google Scholar 

  44. Traynor AE et al. (2002) Hematopoietic stem cell transplantation for severe refractory lupus. Analysis after five years and fifteen patients. Arthritis Rheum 46: 2917–2923

    Article  Google Scholar 

  45. Jayne D et al. (2004) Autologous stem cell transplantation for systemic lupus erythematosus. Lupus 13: 168–176

    Article  Google Scholar 

  46. Kalsi JK et al. (2004) Peptides from antibodies to DNA elicit cytokine release from peripheral blood mononuclear cells of patients with systemic lupus erythematosus: relation of cytokine pattern to disease duration. Lupus 13: 490–500

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Center for Rheumatology and a Professor of Rheumatology,

    David Isenberg & Anisur Rahman

  2. University College London Hospitals, London, UK

    David Isenberg & Anisur Rahman

Authors
  1. David Isenberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Anisur Rahman
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to David Isenberg.

Ethics declarations

Competing interests

Professor Isenberg has consulted for Amgen, Roche, Teva,Immunomedics, Aspreva and Celltech. He does not accept any personal fee; an equivalent sum is donated to an arthritis charity.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Isenberg, D., Rahman, A. Systemic lupus erythematosus—2005 annus mirabilis?. Nat Rev Rheumatol 2, 145–152 (2006). https://doi.org/10.1038/ncprheum0116

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ncprheum0116

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing