Autoimmunity defined

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

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. 

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. 

Vernino, S. and Lennon, V. A. Ion channel and striational antibodies define a continuum of autoimmune neuromuscular hyperexcitability. Muscle Nerve 28 702-707, 2002. 

Kretschmer K, Apostolou I, Jaeckel E, Khazaie K, von Boehmer H Making regulatory T cells with defined antigen specificity role in autoimmunity and cancer. Immunol Rev 2006 212 163-169. 

Based on the kno vledge of the processes of T cell sensitization by chemicals and the importance of T cells in induction of autoimmune diseases a number of key indicators of autoimmunogenic compounds can be defined. These include the possibility to be subject of metabolic conversion (either intra- or extra-hepatically), the capacity to activate dendritic cells, to induce cytokine production (in any cell type), or the potency to cause cell stress or cell death. Most of these processes can be studied in vitro, but none of the available methods have been tested for this purpose and often chemicals may behave completely different in vitro than in vivo. However, much can be learned from initiatives to design alternative methods for contact allergens, as many of these basic processes that lead to T cell sensitization are similar for allergenic and autoimmunogenic chemicals. 

Rheumatic disease is defined as disease of connective tissue and medical disorders of the musculoskeletal system . The medical discipline concerned with these diseases is referred to as rheumatology. The majority of rheumatic diseases are soft tissue rheumatism and nonspecific low back pain (LBP), autoimmune inflammatory rheumatic diseases, osteoarthritis (OA), osteoporosis, crystal-deposition disease and infectious arthritis. 

With the advent of biological-DMARD combinations with Methotrexate (MTX) a new era of therapy in autoimmune disease is introduced. DMARD-refractory autoimmune diseases are treated with combinations of a biological with MTX with achievement of improvements of ACR 20 and ASAS 20 in the majority of patients. A small minority of around 20% obtains improvements of ACR 70 and ASAS 70. ACR responses are American College of Rheumatology response criteria and ASAS stands for Assessment in Ankylosing Spondylitis. ACR and ASAS 20, 50 or 70 scores are exactly defined improvements of respectively 20%, 50% or 70%. 

Pathophysiologically, there is little difficulty in recognizing disseminated intravascular coagulation and then treating this on merit. Much more frequent are immunologically mediated mechanisms that may be secondary to underlying collagen-vascular diseases such as systemic lupus erythematosus or where the defect exists in isolation and the process is defined as primary, idiopathic or autoimmune. 

Until the role of echinacea in immune modulation is better defined, this agent should be avoided in patients with immune deficiency disorders (eg, AIDS, cancer), autoimmune disorders (eg, multiple sclerosis, rheumatoid arthritis), and patients with tuberculosis. While there are no reported drug interactions for echinacea, some preparations have a high alcohol content and should not be used with medications known to cause a disulfiram-like reaction. In theory, echinacea should also be avoided in persons taking immunosuppressant medications (eg, organ transplant recipients). 

Slow viruses are becoming increasingly suspect in the instances of much more common diseases, particularly the autoimmune diseases. An autoimmune disease may be defined as a disease wheiein the immune system of the body does not direct its attack on an invading foreign substance, but instead at the body s own tissue. Many authorities consider rheumatoid arthritis and multiple sclerosis as autoimmune diseases. The precise causes of these diseases have remained obscure. Multiple sclerosis is a demyelinating disease and has variously been described as an autoimmune disease, a viral disease, or an autoimmune disease provoked by a virus. Epidemiological studies indicate that from 3 to 23 years may elapse between the time of exposure to the virus and the onset of symptoms. Further evidence points to involvement of a myxovirus. Measles virus is of this kind. 

The most frequent adverse reactions associated with the administration of proleukin include fever, chills, fatigue, malaise, nausea and vomiting. It has also been associated with capillary leak syndrome (CLS). CLS is defined as a loss of vascular tone and effusion of plasma proteins and fluids into the extravascular space. This leads to hypotension and decreased organ perfusion, which may cause sudden death. Other side effects include anaphylaxis, injection site necrosis and possible autoimmune and inflammatory disorders. 

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