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Protective properties: immune cells will help to cleanse the skin with psoriasis
Scientists have presented new data that brings medicine closer to personalized treatment of psoriasis. Researchers have identified immune cells that can be used to evaluate the effectiveness of therapy and predict the duration of remission. In addition, doctors have tested modern drugs that have made it possible to achieve 90% skin cleansing even in patients with severe forms of the disease. About modern approaches to therapy and new ways of returning patients to a full life, which experts presented for the World Psoriasis Day, in the Izvestia article.
What triggers psoriasis?
Scientists at Sechenov University have obtained new data on psoriasis, which made it possible to better understand the mechanisms of the disease's development and, in the future, select targeted treatment taking into account the characteristics of a particular patient. Researchers have proved for the first time that psoriasis-affected skin has tens and hundreds of times more unique sequences of T-cell receptors than healthy skin.
T-cell receptors are a kind of "eyes" of effector T-lymphocytes, that is, immune cells attacking "enemies". It is these receptors that help the immune system recognize targets. They probably react to certain skin proteins that have yet to be identified, the scientists told Izvestia.
Psoriasis affects the skin, nails, and even joints. In the latter case, it is psoriatic arthritis, which causes stiffness and severe pain in the joints and often leads to disability. It is believed that genetics plays a major role in the development of the disease, but it accounts for only 60-70% of the factors. A trigger mechanism is also needed. These can include, for example, stress, infections, taking certain medications, mechanical damage to the skin, vaccination, disruption of the microbiome, and other factors. All of them can provoke or worsen the development of psoriasis.
The data obtained will allow doctors to evaluate the effectiveness of treatment at the molecular level — by whether the number of pathogenic T cells in the skin is reduced.
— In the future, the data obtained will allow us to create a therapy that will block these T cells. For example, it can be antibodies to their receptors, as well as vaccines or immunotherapy methods that "retrain" the immune system not to attack the skin. All this is the next level of personalized medicine," Olga Olisova, director of the V.A. Rakhmanov Clinic for Skin and Venereal Diseases at Sechenov University, Corresponding Member of the Russian Academy of Sciences, told Izvestia.
Another study by university scientists has shown that there are not enough other cells in the blood of patients that, on the contrary, perform a protective function — regulatory T cells (Tregs). Normally, they work as follows: effector T cells attack, for example, an infectious agent, and regulatory T cells stop this reaction when the enemy is "defeated." In psoriasis, the Treg level is lower — 2.84% versus 4.02% in healthy people. The "defenders" cannot cope with the pressure of the attacking cells, which causes the inflammation to increase and the plaques to grow.
— Perhaps in the future, this discovery will become the basis for a new method of cell therapy: it will be possible to specifically grow and introduce regulatory cells into the human body. Our colleagues conducted an experiment on mice. The cells grown in the laboratory were able to suppress the autoimmune process, despite the fact that the body was simultaneously attacked by aggressive T cells," said Ekaterina Grekova, associate professor at the V.A. Rakhmanov Department of Skin and Venereal Diseases at Sechenov University.
Light therapy and genetically engineered drugs
The clinic's doctors have found a way to increase the level of T-reg using a proven method — phototherapy, that is, exposure to the skin with ultraviolet light. After the course of treatment, the proportion of regulatory cells increased from an average of 2.11% to 3.44%. At the same time, the increase in their number directly correlated with the duration of remission. The results showed that after a course of phototherapy, 60% of the 80 patients who participated in the study had completely disappeared plaques.
In severe cases of psoriasis, more intensive therapy is used. And new approaches are emerging here. New genetically engineered drugs are replacing standard anti-inflammatory and immunosuppressive drugs that can cause side effects. Scientists have tested several such targeted drugs.
Monoclonal antibodies— proteins synthesized in the laboratory, bind to one of the key cytokines, interleukin-17A, and block its action. The drugs neutralize the cytokine before it transmits a signal to the cells that trigger inflammation. One of the studied drugs made it possible to achieve complete skin cleansing in 31% of cases, and in 69% of patients, skin lesions were reduced by at least 90%. The itching almost completely disappeared in all the study participants.
The second drug has shown particular effectiveness in the treatment of psoriasis in areas that are difficult to treat — in the groin, armpits, palms, soles and nails. For example, on the palms and soles, the skin was completely cleansed in 80% of patients, while the remaining 20% showed almost one hundred percent cleansing.
With the help of genetically engineered drugs, it was possible to save a patient whose life was under serious threat, Olga Olisova said. He developed a severe and rare form of psoriasis, generalized pustular psoriasis Tsumbusha, which arose against the background of improper treatment.
— Multiple pustular pustules appeared in place of the dry plaques, the temperature rose sharply, and tests revealed a pronounced inflammatory process. Before contacting us, the doctors at the place of residence tried many drugs, but none helped. We prescribed targeted therapy to the patient, which allowed us to interrupt the cascade of inflammation. The cytokine storm was stopped, and after the third injection, the pustules completely disappeared," she added.
Promising approaches to the treatment of psoriasis
The research of colleagues from Sechenov University is promising and corresponds to the main trend of modern dermatology — personalized treatment, taking into account the characteristics of the immune response of a particular patient, Ekaterina Suvorova, dermatologist at the biotech studio Scanderm, market expert at NTI Helsnet, told Izvestia.
— If the relationship between the level of regulatory T cells and treatment outcomes is confirmed in larger studies, this indicator may become one of the tools for assessing the response to therapy. Data on T-cell receptors will help determine more precisely which immune cells support the disease, and in the future, find ways to target them. This is important because even after the disappearance of plaques in the skin, cells of immunological memory remain, which are associated with relapses.: rashes often appear in the same areas," the expert explained.
Cell therapy using grown regulatory T cells is still an experimental approach. Her results obtained in animal studies have yet to be confirmed in humans, Ekaterina Suvorova emphasized.
The main change in the understanding of psoriasis in recent years is that it is considered not just as a skin disease, but as a systemic autoimmune inflammation, said molecular biologist Arina Kholkina. According to her, scientists have identified two key mechanisms for the development of the disease. Firstly, psoriatic plaques contain dozens of times more unique T-cell receptors. This indicates the diversity of immune cells involved in inflammation, and allows us to evaluate the response to treatment at the molecular level. Secondly, patients have a deficiency of regulatory T cells, which normally should restrain the immune attack. The lower their level, the more aggressive the disease can be and the shorter the remission after treatment.
— Studies show that phototherapy, already used in clinical practice, increases the level of regulatory T cells and helps prolong remission, and genetically engineered drugs specifically block cytokines involved in inflammation. Together, this reflects the principle of personalized medicine: to treat not only skin manifestations, but also a specific link of immune failure in a particular patient," said Arina Kholkina.
Experts also stressed the importance of prevention. Even with a genetic predisposition, the risk of exacerbations may depend on lifestyle. Thus, highly processed products, including fast food, can negatively affect the microbiome, and excess animal fats can disrupt lipid metabolism. Both factors can affect the state of the immune system and the skin. Another way to reduce the impact of provoking factors is to learn how to manage stress, experts noted.
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