Autoimmune conditions

The definition of an overlap syndrome dictates that the criteria for diagnosis of both disorders (in the present context, of PM/DM and of some other connective tissue disorder), are fulfilled. It is not unexpected that those syndromes which overlap with PM/DM are also either known autoimmune conditions or ones in which an autoimmune basis is strongly suspected. The association of these disorders with PM/DM syndromes may not materially alter the basic histopathological featmes expected in PM/DM but some differences may be identifiable. The disorders most frequently associated with an overlap syndrome are rheumatoid arthritis, systemic lupus erythematosis, scleroderma, and mixed connective tissue disease. 

Approximately 30% to 40% of currently licensed drugs are targeted at GPCRs and thus represent a highly significant source of income for many pharmaceutical companies (80). In the specific context of chemokine receptors, it is clear that they are involved in a number of prominent pathologies and thus represent an important therapeutic target (81). For example, chemokines and their receptors lie at the center of all immune and inflammatory disorders and are responsible for the aberrant accumulation of leukocytes at inflamed sites in autoimmune conditions. In addition, over the past 12 years, it has become clear... 

It has been estimated that 1-2 per cent of the US population suffer from autoimmune conditions, including rheumatoid arthritis, MS and some forms of diabetes. In many instances, an autoimmune response results from the inappropriate activation of a specific subset of B- and/or T-lymphocytes. The most common immunotherapeutic approach to potentially treat such diseases is to induce depletion of the individual s T- and B-cell populations. This could be achieved by administration of an antibody raised against a surface antigen present on such cells. Initial trials, for example, have shown that injection of an (unconjugated) anti-CD4 antibody (cell surface glycoprotein present on many T-lymphocytes) over 7 days significantly reduced the clinical symptoms of rheumatoid arthritis for several months. 

No pyrazinothiazine derivatives have been marketed to date. However, the adhesion molecule inhibitor ER-49890 151 is of interest for the treatment of autoimmune conditions <2004GPB675>. 

The anti-phospholipid syndrome refers to a range of autoimmune conditions which are characterised by venous or arterial thrombosis, recurrent strokes, pulmonary embolism, recurrent pregnancy loss or obstetric complications and the presence of circulating antibodies with specificity to a range of phospholipids including phosphatidylserine and cardiolipin. The syndrome is the leading cause of vascular thrombosis in children. It sometimes accompanies other autoimmune conditions such as systemic lupus erythematosus (SLE). 

Kifor et al. (2003) found autoantibodies to the CaR in four patients who had a clinical picture resembling that of FHH in the setting of other autoimmune conditions (e.g., Hashimoto s thyroiditis and sprue). The patients sera stimulated PTH secretion and inhibited high calcium-stimulated inositol phosphate accumulation and MAPK activation, presumably owing to antibody-mediated inhibition of the CaR. Further studies of a larger number of patients are required to determine the incidence of autoimmune, PTH-dependent hypocalciuric hypercalcemia in the presence of various types of autoimmunity. 

Clinical Use. Mycophenolate mofetil (CellCept) is primarily used to prevent or treat organ rejection following cardiac and renal transplantation. This drug is typically combined with other immunosuppressants (cyclosporine, glucocorticoids) to provide optimal immunosuppression in patients receiving these transplant types.39,40,70 Mycophenolate mofetil may also be useful in suppressing the immune response associated with autoimmune conditions such as systemic lupus erythematosus.2... 

Severe autoimmune conditions involving vital organs must be treated aggressively, and undertreatment is as dangerous as overtreatment. In order to minimize the deposition of immune complexes and the influx of leukocytes and macrophages, 1 mg/kg/d of prednisone in divided doses is required initially. This dose is maintained until the serious manifestations respond. The dose can then be gradually reduced. 

The use of Echinacea is not recommended for patients with autoimmune conditions, such as multiple sclerosis and AIDS, or those taking drugs to suppress immune response (e.g., corticosteroids) (Blumenthal, 1998 Gruenwald et al., 2000). However, these recommendations appear to be based on speculation more than rigorous, peer-reviewed research. Research is needed to further support or refute the claim that individuals with autoimmune conditions should not use Echinacea. 

Autoimmune urticaria. This seems to be an underlying basis of many cases of chronic idiopathic urticaria. About one third of patients with chronic urticaria spontaneously develop auto-antibodies directed at the receptor FceRI, located on skin mast cells. Chronic stimulation of this receptor leads to chronic hives. Patients often have other autoimmune conditions, such as autoimmune thyroiditis. 

Genetic susceptibility. This plays an important role in almost all autoimmune conditions. The most significant influence is that of the MHC. The linkage between particular MHC class II allotypes and specific diseases has in some cases been determined in almost all cases these diseases have a strong autoimmune component. 

Endocrine factors. Most autoimmune diseases occur with unequal frequency in males and females. For example. Graves and Hashimoto s are 4-5 times, and SLE 10 times, more common in females, while ankylosing spondylitis is 3-4 times more frequent in males. These differences are believed to be the result of hormonal influences. A second well-documented hormonal effect is the marked reduction in disease severity seen in many autoimmune conditions during pregnancy. Rheumatoid arthritis is perhaps the classic example of this effect. In some cases there is also a rapid exacerbation (rebound) after birth. 

Thalidomide is receiving new interest for use in some autoimmune conditions. What is the history and concern for its use ... 

How to assess a potential link between a vaccine and an autoimmune condition... 

Autoimmunity is much more complex than hypersensitivity. Animal models exist for many autoimmune conditions, and autoimmunity has been clearly demonstrated in humans, although it is a relatively infrequent occurrence. Therefore, the existence of autoimmune disease and the expected consequences cannot be denied. However, the ability of drugs and chemicals to exacerbate or trigger autoimmune disease in either animal models or humans is poorly understood. In fact, of all the possible consequences of immunotoxicity, autoimmunity is unquestionably the least understood. Primarily... 

Immune responses can be directed toward a new nonself antigen that has become nonspecifically absorbed to a cell membrane. This mechanism is essentially the description of the sensitizing potential of a hapten and is one of the reasons why there is some overlap between hypersensitivity reactions and autoimmune conditions. 

Powell JJ, Van de Water J, Gershwin ME. Evidence for the role of environmental agents in the initiation or progression of autoimmune conditions. Environ Health Perspect 1999 107 (Suppl 5) 667-72. 

Scleritis is of similar appearance to episcleritis but much more painful. It is often associated with autoimmune conditions such as rheumatoid arthritis. 

A particular aspect of the immune system is that it develops rather late in life. For example thymus development lasts at least until puberty. Over the last couple of years, the need to consider the special vulnerability of the developing immune system has been discussed [74-77], Developmental immunotoxicology might predispose children to those diseases that have been on the rise in recent decades (e.g., childhood asthma, allergic diseases, autoimmune conditions, childhood infections). Our knowledge, especially across species, is still minimal. There are certain possible critical windows of vulnerability of the developing immune system, such as ... 

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