Auto-immune disorders

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Any of a large group of diseases characterized by abnormal functioning of the immune system that causes the immune system to produce antibodies against the person’s own tissues.  (mayoclinic.com)

It seems likely that environmental factors acting with the genetic predisposition of the patient are responsible for triggering autoimmune disease. A few such triggers have been identified, including a number of drugs that are associated with some forms of lupus, thrombocytopenia, haemolytic anaemia and other autoimmune disorders. Infections can be followed by an autoimmune disease in a few instances such as rheumatic fever followed by a streptococcal infection and Guillain-Barre` syndrome caused by chlamydia.
A great deal of circumstantial evidence suggests that viruses may play a role in initiating some autoimmune diseases. A number of nutrients have been studied including iodine which contribute to the onset of autoimmune thyroid disease. In most cases, however, we do not have clear evidence of a particular environmental trigger of autoimmune disease.

Several mechanisms are thought to be operative in the pathogenesis of autoimmune diseases, against a backdrop of genetic predisposition and environmental modulation. It is beyond the scope of this article to discuss each of these mechanisms exhaustively, but a summary of some of the important mechanisms have been described:
• T-Cell Bypass – A normal immune system requires the activation of B-cells by T-cells before the former can produce antibodies in large quantities. This requirement of a T-cell can be bypassed in rare instances, such as infection by organisms producing super-antigens, which are capable of initiating polyclonal activation of B-cells, or even of T-cells, by directly binding to the β-subunit of T-cell receptors in a non-specific fashion.
• T-Cell-B-Cell discordance – A normal immune response is assumed to involve B and T cell responses to the same antigen, even if we know that B cells and T cells recognise very different things: conformations on the surface of a molecule for B cells and pre-processed peptide fragments of proteins for T cells. However, there is nothing as far as we know that requires this. All that is required is that a B cell recognising antigen X endocytoses and processes a protein Y (normally =X) and presents it to a T cell.
• Aberrant B cell receptor-mediated feedback – A feature of human autoimmune disease is that it is largely restricted to a small group of antigens, several of which have known signaling roles in the immune response (DNA, C1q, IgGFc, Ro, Con. A receptor, Peanut agglutinin receptor (PNAR)). This fact gave rise to the idea that spontaneous autoimmunity may result when the binding of antibody to certain antigens leads to aberrant signals being fed back to parent B cells through membrane bound ligands. These ligands include B cell receptor (for antigen), IgG Fc receptors, CD21, which binds complement C3d, Toll-like receptors 9 and 7 (which can bind DNA and nucleoproteins) and PNAR. More indirect aberrant activation of B cells can also be envisaged with autoantibodies to acetyl choline receptor (on thymic myoid cells) and hormone and hormone binding proteins. Together with the concept of T-cell-B-cell discordance this idea forms the basis of the hypothesis of self-perpetuating autoreactive B cells.
Autoreactive B cells in spontaneous autoimmunity are seen as surviving because of subversion both of the T cell help pathway and of the feedback signal through B cell receptor, thereby overcoming the negative signals responsible for B cell self-tolerance without necessarily requiring loss of T cell self-tolerance.

• Molecular Mimicry – An exogenous antigen may share structural similarities with certain host antigens; thus, any antibody produced against this antigen (which mimics the self-antigens) can also, in theory, bind to the host antigens, and amplify the immune response. The idea of molecular mimicry arose in the context of Rheumatic Fever, which follows infection with Group A beta-haemolytic streptococci. Although rheumatic fever has been attributed to molecular mimicry for half a century no antigen has been formally identified (if anything too many have been proposed). Moreover, the complex tissue distribution of the disease (heart, joint, skin, basal ganglia) argues against a cardiac specific antigen. It remains entirely possible that the disease is due to e.g. an unusual interaction between immune complexes, complement components and endothelium.
• Idiotype Cross-Reaction – Idiotypes are antigenic epitopes found in the antigen-binding portion (Fab) of the immunoglobulin molecule. In this case, the host-cell receptor is envisioned as an internal image of the virus, and the anti-idiotype antibodies can react with the host cells.
• Cytokine Dysregulation – Cytokines have been recently divided into two groups according to the population of cells whose functions they promote: Helper T-cells type 1 or type 2. The second category of cytokines, which include IL-4, IL-10 and TGF-β (to name a few), seem to have a role in prevention of exaggeration of pro-inflammatory immune responses.
Dendritic cell apoptosis – immune system cells called dendritic cells present antigens to active lymphocytes. Dendritic cells that are defective in apoptosis can lead to inappropriate systemic lymphocyte activation and consequent decline in self-tolerance.
Epitope spreading or epitope drift – when the immune reaction changes from targeting the primary epitope to also targeting other epitopes. In contrast to molecular mimicry, the other epitopes need not be structurally similar to the primary one.
The roles of specialized immunoregulatory cell types, such as regulatory T cells, NKT cells, γδ T-cells in the pathogenesis of autoimmune disease are under investigation.

There is no known prevention for most autoimmune disorders.

The goals of treatment are to:
• Reduce symptoms
• Control the autoimmune process
• Maintain the body’s ability to fight disease

Which treatments are used depends on the specific disease and the symptoms the patient presents with.
Some patients may need supplements to replace a hormone or vitamin that the body is lacking. Examples include thyroid supplements, vitamins such as B12, or insulin injections. If the autoimmune disorder affects the blood, the patient may need blood transfusions. People with autoimmune disorders that affect the bones, joints, or muscles may need help with movement or other functions.
Medicines are often prescribed to control or reduce the immune system’s response. They are often called immunosuppressive medicines. Such medicines may include corticosteroids (such as prednisone) and nonsteroid drugs such as azathioprine, cyclophosphamide, mycophenolate, sirolimus, or tacrolimus.
Outlook (Prognosis)
The outcome depends on the disease. Most autoimmune diseases are chronic, but many can be controlled with treatment.
Symptoms of autoimmune disorders can come and go. When symptoms get worse, it is called a flare-up.
Possible Complications
Complications depend on the disease. Side effects of medications used to suppress the immune system can be severe, such as infections that can be hard to control.

The health care provider will do a physical exam. Signs depend on the type of disease.
Tests that may be done to diagnose an autoimmune disorder may include:
• Antinuclear antibody tests
• Autoantibody tests
• CBC
• C-reactive protein (CRP)
• Erythrocyte sedimentation rate (ESR)