Autoimmune diseases/disorders

Autoimmune diseases. Disorders that are characterized by (i) the production of autoantibodies or immune effector cells that are autoreactive to self-peptides and (ii) pathological changes (e.g. tissue infiltration, damage, and/or dysfunction) that resulted from these immune responses against self-antigens ( - autoantigens). 

TNF is a pleiotropic cytokine exerting a wide range of cellular responses, that affect biological processes such as lipid metabolism, coagulation, and insulin resistance and the function of endothelial cells. As a major proinflammatory cytokine TNF is also involved in progression of diseases like cancer, Alzheimer, Diabetes type II, cardiovascular, pulmonary or neurological disorders, and many autoimmune diseases. Blocking the action of TNF clearly reduces its inflammatory potential on various autoimmune disorders like Crohn s disease, rheumatoid arthritis (RA), and psoriasis. 

It is important to use these drag with caution in patients with a history of gastrointestinal disorders, renal disease, or liver impairment. The neuromuscular blocking action of die lincosamides poses a danger to patients widi myasthenia gravis (an autoimmune disease manifested by extreme weakness and exhaustion of die muscles). 

Muscle dysfunction may also present as part of multisystem disease, often involving vascular insufficiency or autoimmune disease. By far the most important of the multisystem and autoimmune diseases are seen as subclasses of the inflammatory disorders. 

If you look in the medical literature, you will often see the term placebo defined as a non-specific treatment. What does it mean to say that a treatment is not specific It could mean that the treatment is effective for many different disorders, rather than for only one particular condition. In this sense, placebos are indeed non-specific. Besides depression, placebos have been shown to affect anxiety, pain, ulcers, irritable bowel syndrome, Parkinson s disease, angina, autoimmune diseases, Alzheimer s disease, rheumatoid arthritis, asthma, gastric function, sexual dysfunction and skin conditions. We know this from the thousands of studies in which placebos have been used as control conditions, against which the effects of medication have been evaluated, and from studies that were specifically designed to assess the placebo effect. 

Some xenobiotics may have divergent mechanisms of autoimmune responses. For example, hydralazine demonstrates adduct reactivity as well as inhibition of DNA methylation [68,73], while procainamide inhibits DNA methylation, forms immunogenic NPA, and disrupts clonal selection in the thymus [68, 72, 74], It is this complicated pattern of effects that makes assessment of autoimmune potential in the laboratory for new xenobiotics almost impossible. Animal models can sometimes be recreated to resemble human disease [74], and thus may be useful for therapy considerations, but are difficult to utilize for screening chemicals for hazard potential due to the diverse nature of autoimmunity mechanisms and physiological presentation. While evidence supports many different mechanisms for xenobiotic-induced autoimmune reactions, none have conclusively demonstrated the critical events necessary to lead to the development of autoimmune disease. Therefore, it is difficult to predict or identify xenobiotics that might possess the potential to elicit autoimmune disorders. 

Many mysteries remain to be solved in the immunopathogenesis of autoimmune diseases. Clearly, this group of disorders constitutes an important threat to human health and well-being. They, moreover, represent a fascinating problem for the investigator at the interface of immunology and toxicology. 

Wandl, U.B. et al., Lupus-like autoimmune disease induced by interferon therapy for myeloproliferative disorders, Clin. Immunol. Immunopathol., 65, 70, 1992. 

Antimetabolites. This class of drugs includes purine, pyrimidine, and folic acid analogs that have been successfully used to treat various carcinomas, autoimmune diseases, and dermatological disorders such as psoriasis. Because of their structural similarities to normal components of DNA and RNA synthesis, they are capable of competing with the normal macromolecules and alkylating biological nucleophiles. 

In general, immunosuppression, expansion of regulatory cells, costimulatory blockade, or promotion of a Th2 cytokine milieu is considered to be supportive of disease control in T-cell regulatory disorders such as autoimmune disease and graft-versus-host disease (GvHD) [2]. In contrast, killer cells, a Thl cytokine milieu, or activated lymphocyte infusions support control of malignancy and infections. Maintaining a balance between the two... 

Polyneuritis is a disorder of the peripheral nerves. It involves damage to the myelin sheath. The condition is due to inflammation of the axonal membrane caused by viral or bacterial attack, i.e. an antoimmnne disease. Guillain-Barre syndrome is one form of polynenritis and is an example of an autoimmune disease caused by immune mimicry in response to a bacterial or viral antigen. It is discnssed in Chapter 17. 

Psoriasis is an autoimmune disease that affects the skin as well as the joints. As is the case with many autoimmune disorders, the exact causes of psoriasis are unclear however, it is presumed that an accumulation of toxins in the body may be the root cause. 

Soft tissue rheumatism can be one of the many manifestations of an underlying specific autoimmune disease. Secondary fibromyalgia and enthesitis are the consequences of long-term inadequately treated autoimmune diseases. When no specific underlying causes can be detected, the disorder is called nonspecific soft tissue rheumatism. The major manifestations of soft tissue rheumatism are non-specific... 

Extra-articular manifestations of autoimmune inflammatory disorders indicate severe disease. These manifestations may occur in the eye, neurocerebral and cardiovascular system, kidney, hematopoietic system and hepato-gastrointestinal organs. The systemic extra-articular progression of autoimmune inflammation shortens a patient s life in SLE, SpA, and RA. 

Interferons are contraindicated in individuals with autoimmune hepatitis or other autoimmune disease, uncontrolled thyroid disease, severe cardiac disease, severe renal or hepatic impairment, seizure disorders, and CNS dysfunction. Immunosuppressed transplant recipients should not receive interferons. Interferons should be used with caution in persons who have myelosuppression or who are taking myelosuppressive drugs. Preparations containing benzyl alcohol are associated with neurotoxicity, organ failure, and death in neonates and infants and therefore are contraindicated in this population. Interferons should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. 

Cyclosporine appears to have promise in the treatment of autoimmune diseases. It has a beneficial effect on the course of rheumatoid arthritis, uveitis, insulin-dependent diabetes, systemic lupus erythematosus, and psoriatic arthropathies in some patients. Toxicity is more of a problem in these conditions than during use in transplantation, since higher doses of cyclosporine are often required to suppress autoimmune disorders. 

Although corticosteroids possess immunosuppressive properties, their real value is in controlling the inflammation that can accompany transplantation and autoimmune disorders. Virtually all phases of the inflammatory process are affected by these drugs. Corticosteroid therapy alone is successful in only a limited number of autoimmune diseases, such as idiopathic thrombocytopenia, hemolytic anemia, and polymyalgia rheumatica. 

Worldwide, the most common thyroid disorder is hypothyroidism resulting from dietary iodine deficiency. In iodine-replete areas of the world, most thyroid disorders are the result of autoimmune disease. The symptoms manifested in hypothyroid and hyperthyroid states are largely independent of any underlying disorder of the thyroid gland itself they are a function of the degree of hormone deficiency or excess. 

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