Glomerulonephritis, autoimmune

Hematologic diseases autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura, pernicous anemia Kidney disease Goodpasture syndrom, lipoid nephroses, minimal change glomerulonephritis Diseases of the gastrointestinal tract autoimmune chronic active hepatitis, autoimmune atrophic gastritis, Crohn s disease, ulcerative colitis... 

In the pathogenesis of many chronic inflammatory diseases (e.g., rheumatoid arthritis, glomerulonephritis, colitis ulcerosa, Morbus Crohn, atopic dermatitis, psoriasis) autoimmune processes play an important role, too. Although first of all nonsteroidal antiinflammatory agents or glucocorticoids should be applied, immunosuppressive agents may also be indicated. 

Penicillamine onset may be seen in 1 to 3 months, and most responses occur within 6 months. Early adverse effects include skin rash, metallic taste, hypogeusia, stomatitis, anorexia, nausea, vomiting, and dyspepsia. Glomerulonephritis may occur, which manifests as proteinuria and hematuria. Penicillamine is usually reserved for patients who are resistant to other therapies because of the rare but potentially serious induction of autoimmune diseases (e.g., Goodpasture s syndrome, myasthenia gravis). 

Nassberger, L. et al., Antibodies to neutrophil granulocyte myeloperoxidase and elastase Autoimmune responses in glomerulonephritis due to hydralazine treatment, J. Intern. Med., 229, 261, 1991. 

Brown Norway rat HgCl2 AU-salts D-Penicillamine Nevirapine HCB IC-glomerulonephritis Skin pathology, dermatitis Polyclonal IgE AutoAb (Type IV-collagen, ANA, 1 anti-ACh, thyroglobulin) Systemic inflamatory response with autoimmune symptoms... 

Nitrofurantion D-Penicillamine Peripheral neuritis Autoimmunity drug-induced SLE, myasthenia gravis, pemphigus, glomerulonephritis, Goodpasture s disease... 

Kidney Amyloisosis Glomerulonephritis (immune complex) Autoimmunity... 

The main clinical uses of immunosuppressive drugs are suppression of organ and tissue rejection after transplant surgery and the treatment of diseases with an autoimmune component. Thses include renal diseases, e.g. glomerulonephritis, some nephrotic syndromes, connective tissue diseases, such as systemic lupus erythematosus rheumatoid arthritis, and systemic vasculitis. 

Azathioprine and mercaptopurine appear to be of definite benefit in maintaining renal allografts and may be of value in transplantation of other tissues. These antimetabolites have been used with some success in the management of acute glomerulonephritis and in the renal component of systemic lupus erythematosus. They have also proved useful in some cases of rheumatoid arthritis, Crohn s disease, and multiple sclerosis. The drugs have been of occasional use in prednisone-resistant antibody-mediated idiopathic thrombocytopenic purpura and autoimmune hemolytic anemias. 

The effectiveness of immunosuppressive drugs in autoimmune disorders varies widely. Nonetheless, with immunosuppressive therapy, remissions can be obtained in many instances of autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura, type 1 diabetes, Hashimoto s thyroiditis, and temporal arteritis. Improvement is also often seen in patients with systemic lupus erythematosus, acute glomerulonephritis, acquired factor VIII inhibitors (antibodies), rheumatoid arthritis, inflammatory myopathy, scleroderma, and certain other autoimmune states. 

Type III Reactions These reactions involve the presence of antigen-antibody complexes, particularly those formed as a result of the production of autoantibodies. These complexes deposit in various tissues and involve inflammatory cells as well as complement, resulting in tissue damage due to the production of proteolytic enzymes by polymorphonuclear leukocytes and macrophages. A number of autoimmune diseases result from these reactions. Some clinical examples include systemic lupus erythematosus, rheumatoid arthritis, immune complex glomerulonephritis, Arthus reaction and serum sickness. 

Naked pDNA delivery of cytokines has also been evaluated in a number of mouse models of autoimmune disease. Naked pDNA delivery of TGF/3 to a murine model of systemic lupus erythematosus (SLE) led to lower serum IgG levels, decreased glomerulonephritis and increased survival (Raz et al., 1995). The pDNA (100 gg) was injected i.m. at 6, 10, 14, 18 and 22 weeks. Administration of IL-2 encoding pDNA had the opposite effect, resulting in increased semm IgG, increased glomerulonephritis, and decreased survival, demonstrating that a disease course could be significantly modulated by naked pDNA therapy. The pDNA (100 gg) was injected once in every two weeks for a total of five injections. Circulating semm levels of either IL-2 or TGF 0 w ere detected up to two weeks after the final pDNA injection into the muscle. 

Azathioprine is an effective agent in suppressing the immune system in patients undergoing renal transplantation and in patients suffering from acute glomerulonephritis, the renal component of systemic lupus erythematosus, prednisone-resistant idiopathic thrombocytopenic purpura, and functioning autoimmune hemolytic anemia. Azathioprine depresses bone marrow functioning, which is its chief side effect. 

Guery JC, Druet E, Glotz D, Hirsch F, Mandet C, De Heer E,and Druet P. Specificity and cross-reactive idiotypes of anti-glomerular basement membrane autoantibodies in HgCl2-induced autoimmune glomerulonephritis. European Journal of Immunology 20 93-100,1990. 

Over the past decade there has, as result of experimental studies, been a growing appreciation that mercury may exert an effect on the immune system. As summarized by Silbergeld and Devine [72], mercury has at least two types of effects on the immune system. First, mercury induces autoimmunity to renal basement membrane proteins, causing mercury-induced glomerulonephritis in certain strains of mice and rats. Secondly, mercury exposure impairs cell-mediated and humoral immunity by affecting Thl and Th2 responses, which in turn impairs the body s ability to effectively... 

Hua J, Pelletier L, Berlin M, Druet P. Autoimmune glomerulonephritis induced by mercury vapour exposure in the Brown Norway rat.Toxicology 1993 79 119-29. 

Hirszel P, Michaelson JH, Dodge K, et al. 1985. Mercury-induced autoimmune glomerulonephritis in inbred rats—part II. Immunohistopathology, histopathology and effects of prostaglandin administration. Surv Synth Pathol Res 4 412-422. 

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