In a couple of animal studies, it was determined that the immune system can be trained to onslaught itself to reverse a disturbing autoimmune disease. American researchers treated Pemphigus vulgaris in mice by setting off a “civil war” within the immune system. They are very confident that the same approach could work with humans.
Pemphigus vulgaris is an uncommon autoimmune disorder that involves sores and blistering of the skin and the mucus membrane. It usually affects middle-aged or older individuals. With this particular condition, the immune system makes antibodies that fight specific proteins in the mucus membranes and skin. These types of antibodies damage the bonds between skin cells and leads to blister formation. Until today, the exact cause of Pemphigus vulgaris is still unknown.
At times, this disorder is caused by some medications, although this is uncommon. Medications that might cause this disorder include ACE inhibitors (blood pressure medications) and penicillamine (a drug that removes some materials from the blood).
More or less half of the individuals suffering from this condition initially develop sores and blisters in their mouth, followed by skin blisters. Sores may reappear anytime. The skin sores may be characterized as oozing, draining, crusting, and peeling. These are located in the mouth, trunk, scalp and other areas of the skin.
Several experts have mentioned that the treatment that the Journal Science published was both creative and successful. This treatment reengineers “chimeric antigen receptor T cells” to target autoimmune disease.
In an ideal world, the remedy for autoimmune diseases must eradicate pathogenic autoimmune cells, while protecting the immunity, however, possible strategies for such approach have been intangible. The American researchers show that in the pemphigus vulgaris (PV), the chimeric immunoreceptors can control T cells to destroy autoreactive B lymphocytes through the B cell receptor or BCR.
The US researchers engineered human T cells to express a CAAR or chimeric autoantibody receptor. CAAR-T cells might offer an effective and general strategy for “specific targeting of autoreactive B cells in antibody-mediated autoimmune disease.”
Autoimmune disorders resulted from the defenses of the body turning rascal and attacking healthy tissue. In some cases, this condition can be deadly.
Pemphigus vulgaris can be treated by using medicines to relax the entire immune system, but that kind of treatment can leave a person more susceptible to infection.
Using a patient’s immune system as a weapon to battle against the disease is already providing outstanding results in cancer.
One recent approach is to re-engineer T-cells, which usually specializes in tearing down infected cells, to instead attack the cancerous cells.
Using these modified T-cells have helped 90% of terminally ill leukemia patients to go into remission.
Also known as T lymphocyte, T-cell is a type of white blood cell or leukocyte that plays a crucial role in the immune system. These cells are one of the two major types of lymphocytes; the other one is called B-cells. These cells identify the specificity of “immune response to foreign substances or antigens in the body.
The acronym “T” means thymus. These cells begin in the bone marrow and fully develop in the thymus. In this area, they reproduce and separate into regulatory, helper, or cytotoxic T-cells or develop into memory T-cells. The Regulatory T-cells manipulate the immune reactions, while the helper secretes cytokines (chemical messengers). On the other hand, the cytotoxic T-cells are activated by numerous cytokines and kill cancer and infected cells.
The human body contains millions of B and T cells, most of them carry unique receptors. Because of these, they can react with practically any antigen.
Every single successful immune response includes T-cell activation; however, they are essential in cell-mediated immunity, which is the protection against tumor cells and pathogenic organisms in the body cells.
The University of Pennsylvania researchers refined the strategy to alter the targeting mechanism on T-cells so they fight only the fraction of the immune system that causes Pemphigus vulgaris.
The mice experiments showed the characteristic blistering could be interrupted, without leaving any effect on the rest of the immune system.
Michael Milone, an assistant professor and one of the researchers thinks that the experiment was an “incredibly exciting time.” They were equipped with tools to control immunity that they have never before.
He added that immunotherapy is actually changing treatment for cancer, and they were just at the foundation for autoimmunity.
Milone believes that the line of attack could also work in similar diseases where there is an evident antibody causing the issue like in the case of Myasthenia gravis.
Nevertheless, other autoimmune disorders like type-1 diabetes, multiple sclerosis, and lupus have very complex causes that are difficult to treat.
According to Aimee Payne, an associate professor, the therapy could work in patients, but she wished to do more animal research first. Currently, they have shown similar data as her cancer colleagues did. However, there was concern about causing danger when the disease is not at its terminal stage. Their goal is to treat it in dogs, and if that succeeds, then it is highly possible to overcome barriers to patients.
Every T-cell has a targeting system that can distinguish enemies in the body.
The US research team modified the T-cells by combining a new targeting mechanism onto them to produce CAR-T cells (chimaeric antigen receptor T-cells).
In the case of Pemphigus vulgaris, the body mistakenly creates antibodies to attack desmoglein (a protein), which is usually the bond that holds the skin cells together.
The researchers used desmoglein to direct their CAR-T cells to only the white blood cells making the antibodies.
According to Prof Danny Altmann, from the British Society of Immunology, the “CAR-T cell technology has been a wonderful innovation.”
He loves what the US researchers have done, which was very creative, and relatively successful. This is not just a mouse paper in the field of Science, it is a little leap to “being transplantable” to a medical trial.
Furthermore, any treatment that produces similar results is expected to be very expensive.
At the end, the research provides a new milestone and gives more hope to those lives affected with Pemphigus vulgaris and other autoimmune diseases.