Autoimmune diseases (AID) occur when the body's immune system recognize itself as non-self and acts against it as foreign particle or pathogen. It reacts against some of its own cells and tissue(s) by producing antibodies against it known as autoantibodies. Examples of autoimmune diseases include rheumatoid arthritis, systemic lupus erythematosus, myasthenia gravis, multiple sclerosis, psoriasis juvenile diabetes, antiphospholipid syndrome, alopecia, Crohn's disease, cardiomyopathy, Guillain-Barre syndrome, Sjogren's syndrome, and Graves' disease. Autoimmune diseases are broadly categorized into organ-specific and systemic autoimmune diseases. Five to seven percent of the world population is affected by autoimmune diseases, mostly causing chronic debilitating ailments. It is expected that the treatment for autoimmune diseases should be aimed at reducing particularly the autoimmune response without causing any untoward effects to the rest of the immune system. Unfortunately, this target has not been achieved till date and we have been depending on the palliatives modes of treatment aimed at relieving the pain or symptoms; at least to enhance the quality of life. Here, we are going to discuss some treatment procedures of autoimmune diseases with their advantages and limitations.
Immunosuppressive drugs: One of the most obvious treatments of autoimmune diseases includes the immunosuppressive medications that inhibit or prevent activity of the immune system. In turn, these treatments cause nonspecific suppression of immunity and thus are not able to distinguish between a protective and a pathologic immune response but in general, these can reduce the severity of autoimmune symptoms. Immunosuppressive drugs such as corticosteroids, cyclophosphamide, azathioprine, etc., are basically given to slow down the proliferation of lymphocytes. As a consequence of this immunosuppression, greater risk for infection or the development of cancer may be faced by the patients. Drugs such as cyclosporin A or FK506 provide somewhat more selective approach to treat autoimmunity by blocking T-cell receptor mediated signal transduction inhibiting antigen-activated T cells only, unaffecting the nonactivated T-cells. Another therapeutic approach that has produced positive results in some cases of myasthenia gravis is removal of the thymus. Because patients with this disease often have thymic abnormalities (e.g., thymic hyperplasia or thymomas), but adult thymectomy often increases the likelihood of remission of symptoms moreover there are so many dangerous after effects of this surgery.
Plasmapheresis is a procedure which has given short-term benefits to patients with rheumatoid arthritis, systemic lupus erythematosus, Graves' disease or myasthenia gravis. Autoimmune diseases involving antigen-antibody complexes are of special emphasis for plasmapheresis, because of the removal of the complexes resulting in a short-term reduction in symptoms.
T-cell vaccination as a therapy for some autoimmune diseases has been quite successful in the experimental animals of experimental allergic encephalomyelitis (EAE) but has not been successful in humans yet.
MHC blockade: Synthetic peptides mimicking myelin basic protein, differing by only one amino acid have been shown to bind to the corresponding major histocompatibility complex molecules resulting in their blockade, hence contribute to the suppression of the clinical development of EAE in mice. Here also, the therapeutic development is still in its infancy.
Monoclonal Antibody treatments: Monoclonal antibodies have been posed to be a promising effort towards the treatment of autoimmunity and have been used successfully to treat several autoimmune diseases. Regardless of their specificity, monoclonal antibodies can threaten the overall immune responsiveness of the patient. One remedy for this disadvantage is to block antigen activated TH cells only, since these cells are involved in the autoimmune state.
Reduction of T cells: Monoclonal anti-T-cell antibodies injections have also proven to be effective in some animal models. However, in human application, it has been challenging, which may include the murine monoclonal immunogenicity, the deleterious and unexpected effects of generalized T-cell activation, and T-cell elimination.
Co-Stimulatory Signal Blockade: Co-stimulatory signals are important components for T-cell activation. Induction of energy by disrupting co-stimulatory interactions was believed to fetch hopeful results but has been limited to animal models only and that too with variable results.
Induction of tolerance: Based on the encouraging results obtained from animal studies, oral tolerization has also come up as a significant approach. EAE mice were administered with oral doses of myelin proteins and arthritic rats with collagen type II. In addition, oral tolerization is devoid of side effects. On the contrary, the data from humans is not so beneficial. However, the human clinical trials are in the early stages, so we can expect the promising results of this approach as beneficiary for humans also in the coming years. Some of the other approaches to treat autoimmune diseases are injection of a normal pool of immunoglobulin (IVIG) and use of immunotoxins. These approaches also not have met with great success.
In conclusion, immunologists have been studying the mechanisms of tolerance and autoimmunity since last two decades, but our knowledge is still in its infancy, as reflected. There has been much left to study for the better therapy of autoimmune diseases for the cure in safer ways.
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Written by Debasis Sahu and Shikha