Autoimmune Disease: Treatment

Abstract

In recent years, substantial progress has been made in understanding the mechanisms of inflammation and autoimmunity, providing new targets for the development of new treatment principles. Tumour necrosis factor α (TNFα) antagonists have been proven as a major progress in the treatment of different rheumatic and chronic inflammatory bowel diseases. The interleukin 1 (IL‐1) receptor antagonist has considerably improved our medication for the systemic juvenile arthritis and periodic fever syndromes, an anti‐IL‐6 receptor monoclonal antibody might be of value as well as abatacept, a cytotoxity lymphocyte‐associated antigen 4Ig (CTLA‐4Ig) fusion protein for the treatment of patients with rheumatic diseases who do not respond to TNF antagonists. The same is true for rituximab, a chimeric anti‐CD20 antibody.

Key concepts

  • Mode of action and indications for the treatment with traditional and new (cyclooxygenase II, COX‐II, inhibitors), Nonsteroidal anti‐inflammatory drugs (NSAIDs).

  • Mode of action and indications of steroids for the treatment of autoimmune and chronic inflammatory diseases.

  • Disease modifying and immunosuppressive drugs, there are different modes of action.

  • The limitation of surgical approaches in the treatment of autoimmune and chronic inflammatory diseases such as thymectomy, splenectomy and synovectomy.

  • The limitation of radiotherapy and total lymphoid irradiation for the treatment of autoimmune diseases.

  • The limitation of plasmapheresis and leucapheresis as treatment principles for autoimmune diseases.

  • Cellular and juvenile targets for immune intervention in autoimmune and chronic inflammatory diseases.

  • Biologics for the treatment of autoimmune and chronic inflammatory diseases, modes of actions.

  • Monoclonal antibodies and fusion proteins for targeting T cells, B cells, cytokines and adhesion molecules.

  • Mechanisms that could help to reestablish self‐tolerance as well as the ultimate therapeutic goal in autoimmune diseases.

Keywords: immunomodulatory therapy; autoimmune disease; monoclonal antibody therapy; cytokine antagonism; tolerance induction; modulation of T cells

Figure 1.

Potential therapeutic effects of monoclonal antibodies directed to proteins expressed on the cell surface of T cells: (1) induction of cytotoxic effects upon interaction of the Fc part of the antibody with Fc receptors on phagocytes; (2) activation of the complement cascade leading to the formation of the cytolytic membrane attack complex and to chemoattraction of phagocytes; (3) interference with T‐cell activation by blocking of T‐cell receptor costimulation; (4) modulation of the T‐cell response by alteration of the costimulatory signals. The modulated costimulation may give rise to a shift of cytokine release from a TH1‐dominated profile (IFNγ, IL‐12) towards a TH2 pattern (IL‐4, IL‐10).

Figure 2.

Immunomodulatory strategies targeting pro‐inflammatory cytokines: (1) blocking of the respective cytokine by the application of neutralizing monoclonal antibodies; (2) administration of a recombinant receptor antagonist that can bind to the receptor molecule but will not trigger the signalling cascade that is usually activated by the cytokine; (3) neutralization of the cytokine by recombinant soluble cytokine‐receptor constructs. All the strategies prevent the cytokine (e.g. IL‐1 or TNFα) from engaging with its respective cell surface receptor.

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Kalden, Joachim R, and Burkhardt, Harald(Mar 2009) Autoimmune Disease: Treatment. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0001437.pub2]