Autoimmune rheumatoid arthritis

The first human kidney and bone marrow transplants using cyclosporine were reported in 1978. Oral or intravenous cyclosporine is an immunosuppressant for transplantation of these and other organs and investigations are underway for its possible use in a variety of autoimmune diseases including rheumatoid arthritis, severe psoriasis, and Crohn s disease. Dose-dependent nephrotoxicity (261—264) remains the primary limitation of the dmg and necessitates close monitoring of patients, including measurement of dmg levels in blood. Cyclosporine research has been reviewed (265—274). 

Inflammatory and immune diseases Autoimmune disease (A,I), asthma (A), osteoarthritis (I), rheumatoid arthritis (I), septic shock (A,I), infections (A,I), familial cold auto-inflammatory syndrome (I), Muckle Wells syndrome (I), chronic infantile neurological cutaneous and articular syndrome/neonatal onset multisystemic inflammatory disease (CINCA/NOMID) (I), Crohn s disease (I), gout (I), acute renal failure (A,l)... 

Immune defense mechanisms can become deleterious for an individual when they are not controlled properly. Then they can cause disease. In such situations therapy is aimed to dampen immune reactions. Important examples are sqttic shock, allergy, autoimmune diseases, and chronic inflammatory diseases such as rheumatoid arthritis. Also, the success of organ transplantation... 

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. 

IFN- 3 reduces the induction by inflammatory cytokines of adhesion molecules and of MHC class I and II complex on endothelial cells, a process preceding attachment and transendothelial migration of T-cells. These anti-inflammatory effects of IFN- 3 exemplify antagonistic actions of type I and type IIIFN. There is, indeed, much clinical evidence for the involvement of IFN-y in inflammatory processes - through activation of iNOS and subsequent secretion of NO - leading to the establishment of autoimmune diseases as for instance in rheumatoid arthritis. 

Rheumatoid arthritis (RA) is a chronic inflammatory disease of unknown aetiology with some autoimmune features. Current thinking favours the hypothesis that interplay between genetic factors, sex hormones, and possibly an infectious agent or another immune activating agent initiates an autoimmune pathogenic mechanism that culminates in a disease with inflammatory and destructive features. 

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. 

Feldmann M, Miani RN (2003) TNF defined as a therapeutic target for rheumatoid arthritis and other autoimmune diseases. Nat Med 9 1245-1250... 

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. 

CCR5 expression likely plays a role in T-cell recruitment and may be involved in the development of autoimmune diseases. There is a negative association between the CCR5A32 mutation and rheumatoid arthritis (Prahalad 2006). Furthermore, additional studies reviewed elsewhere suggest the involvement of CCR5 in multiple sclerosis, diabetes, and transplant rejection (Ribeiro and Horuk 2005). As such, it is likely that CCR5 antagonists developed for the treatment of HIV-1 infection can also be used for other diseases. 

Chronic autoimmune disorders or infections, such as human immunodeficiency virus (HIV) infection or rheumatoid arthritis (anemia of chronic disease)... 

Besides anemia associated with cancer and CKD, anemia of chronic disease can result from inflammatory processes and occurs commonly in autoimmune disorders such as rheumatoid arthritis and systemic lupus erythematosus. In treating these types of anemia of chronic disease, the most important principle is treating the underlying disease. These patients also may have iron deficiency and should be treated in the manner already discussed. Erythropoietin therapy such as epoetin-alfa therapy at a dose of 150 units/kg three times a week also may be used in these patients. 

Pettit AR, Thomas R. Dendritic cells the driving force behind autoimmunity in rheumatoid arthritis Immunol Cell Biol 1999 77(5) 420-427. 

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. 

Thiopurine methyltransferase (TPMT) catalyzes the S-methylation of thiopurine dmgs, such as 6-mercaptopurine (6-MP), 6-thioguanine and azathioprine, to inactive metabolites [29-32]. Thiopurines form part of the routine treatment for patients with acute lymphoblastic leukemia, rheumatoid arthritis, and autoimmune diseases such as SLE and Crohn s disease, and are used as an immunosuppressant following organ transplantation. 

Deficiency of thiopurine S-methyl transferase (TPMT) is another phenotype that exhibits inter-ethnic differences in frequency. TPMT is an enzyme that catalyzes methylation of therapeutic agents used in the treatment of acute lymphoblastic leukemia, rheumatoid arthritis, and autoimmune/inflammatory diseases, as well as in organ transplantation. Patients who have TPMT deficiency experience less efficient methylation and are at greater risk of fatal toxicity when treated with standard doses of fhiopurines. TPMT phenotype is defined by erythrocyte 6-mercapto-purine methylation. African American populations exhibit a 20% lower erythrocyte TPMT than Caucasian Americans, and persons of Chinese descent tend to exhibit greater activity than either of these other American subpopulations. 

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. 

The overall effect of Li+ on the hematopoietic system is of stimulation of the immune system. Not surprisingly then, Li+ is reported to exacerbate the activity of a number of autoimmune diseases, such as psoriasis [212] and rheumatoid arthritis [213], and to result in the production of autoantibodies in some patients [214]. However, there is no evidence that Li+ s stimulation of the immune system leads to any reduction in the occurrence of viral or bacterial infections in patients on Li+ therapy. 

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