IMMUNOLOGY - Roit A. - Mir 2000

Chapter 28. Autoimmune Processes and Autoimmune Diseases

TREATMENT

Symptoms of organ-specific autoimmune diseases can often be alleviated by metabolic correction. Hypothyroidism, for instance, is cured by administering thyroxine, and thyrotoxicosis by antithyroid drugs. In pernicious anemia, the patient's condition can be normalized through vitamin B₁₂ injections, while in myasthenia gravis, cholinesterase inhibitors are used. In cases where impaired function cannot be compensated for by hormone replacement, such as in lupus nephritis or chronic rheumatoid Arthritis, organ transplantation or mechanical prostheses may be effective. Tissue transplantation requires protection against the very immunological process that necessitated the transplant in the first place.

The Immune Response can be suppressed using conventional immunosuppressive therapy with antimitotic agents; however, given the associated hazards, such drugs are reserved exclusively for life-threatening conditions such as SLE and dermatomyositis. The potential of cyclosporine and similar agents has not yet been fully realized, but striking results have been reported in their application to type I Diabetes Mellitus. Anti-inflammatory drugs are naturally employed in treating rheumatoid arthritis patients, with low-dose Steroids yielding very encouraging results in the Cytology/cytology/16.html">Early stages of the disease (to correct a clear impairment in adrenal hormone production).

As our understanding of the pathophysiology of autoimmune diseases deepens and our ability to modulate the patient's immunological status expands, other currently less explored therapeutic approaches may also find application (Fig. 28.27). For example, in certain experimental autoimmune diseases, tolerance can be induced by oral administration of the antigen, inhalation of autoantigenic Peptides and their analogues, and 'vaccination' with peptides derived from antigen-specific receptors of autoreactive T Cells. These findings suggest that stimulating normal suppressive mechanisms, including the idiotype network, is a promising therapeutic strategy for autoimmune diseases.

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Fig. 28.27. Current Methods for blocking the pathological process in autoimmune diseases are listed against a blue Background, and potential future approaches against a green background. In severe cases of SLE or chronic active hepatitis, antimitotic agents are used, whereas anti-inflammatory drugs are widely applied in rheumatoid arthritis. In organ-specific diseases (such as primary Myxedema), replacement therapy (e.g., THYROID Hormones) can be utilized. When transplantation is necessary, immunosuppressive therapy can protect the grafted tissue from destruction.

Questions for Structure/133.html">Discussion

■ Why should DNA not be a Thymus-dependent autoantigen, and what mechanisms might render it such?

■ What evidence indicates the pathogenic role of autoantibodies in disease?

■ Mice were transgenic for 1) the lymphocytic choriomeningitis (LCM) virus glycoprotein under the control of the Insulin Gene promoter, and 2) the TCR of a T-Cell clone cytotoxic to LCM virus-infected cells. Diabetes developed only upon infection of the mice with LCM virus. What does this indicate?

■ How might specific MHC haplotypes determine predisposition to certain autoimmune diseases?

■ What insights into the genesis of autoimmune diseases have been gained from using OS strain chickens as a research model?

■ How would you attempt to target T cells for the Treatment of an autoimmune disease?

Introduction/47.html">Further Reading

Albani S., Keystone Е.С., Nelson J.L. et al. 1995. Positive Selection in autoimmunity: abnormal immune responses to bacterial dnaJ antigenic determinant in patients with early rheumatoid arthritis. Nat. Med. 1:448-52.

Bach J.-F. (ed). 1996. Symposium on autoimmunity. J. Autoimmun. 9: 205-304.

Brostoff J., Scadding G.K., Male D. et al. 1991. Clinical Immunology. London: Gower Medical Publishing.

Chapel H.M., Haeney M. 1992. Essentials of Clinical Immunology. 3rd edn. Oxford: Blackwell Scientific Publications.

Gelfand E.W. (ed.) 1996. Intravenous immune globulin: Mechanisms of action and model disease states. Clin. Exp. Immunol. 104 (Suppl 1): 1-97.

Kingsley G., Lanchbury J., Panayi G. 1996. Immunotherapy in rheumatic disease. Immunol. Today 17: 9-12.

Lanzavecchia A. 1993. identifying strategies for immune intervention. Science 260: 937.

Lokki M.-J., Colten H.R. 1995. Genetic deficiencies of Complement. Ann. Med. 27: 451-9.

Lichtenstein L.M., Fauci A.S. (eds.) 1996. Current Therapy in Allergy, Immunology and Rheumatology. St Louis, USA: Mosby.

Peter J.B., Shoenfeld Y. (eds.) Autoantibodies. Amsterdam: Elsevier.

Rademacher T., Williams P., Dwek R.A. 1994. Agalactosyl glycoforms of IgG autoantibodies are pathogenic. Proc. Natl. Acad. Sci. USA 91: 6123-7.

Rich R.R., Fleisher T.A., Schwartz B.D. et al. (eds). 1996. Clinical Immunology: Principles and Practice. Vols I & II. St Louis, USA: Mosby.

Vandenbark A.A., Chou Y.K., Whitham R. et al. 1996. Treatment of multiple sclerosis with T-cell receptor peptides. Nat. Med. 2: 1109-15.

Weiner H.L., Mayer L.F. eds. 1996. Oral tolerance: mechanisms and Applications. Ann. N. Y. Acad. Sci. 778 453.

Wicker L., Wekerle H. (eds). 1995. Autoimmunity. Curr. Opin. Immunol. 6: 783-852. (Several critical essays in each annual volume.)