2023-08-30 03:37:20
Research by specifying the house dust mite antigen, which accounts for about 70% of the prevalence of atopy
The IP-10 factor secreted by house dust mites activates the infiltrated lymphocytes in the affected area to aggravate the condition.
Discovery of new immune factors that can effectively control inflammation caused by house dust mites
Under development of new drug candidates that effectively control IP-10, are less toxic and have excellent skin penetration
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[바이오타임즈] A research team in Korea has found a clue to a new treatment for sensitive, severe chronic atopic dermatitis caused by house dust mites.
The National Research Foundation of Korea announced that a research team led by Professors Choi Young-ae, Jang Yong-hyun, and Kim Sang-hyun at Kyungpook National University School of Medicine discovered an important factor responsible for the malignant link of sensitive chronic atopic dermatitis caused by house dust mites. The results of this study were published online on August 7 in Allergy, the top international journal in the field of allergy.
Atopic dermatitis is a disease with a prevalence of 15 to 25% worldwide and has been continuously increasing for the past 20 years. The number of domestic patients who have been treated for atopic dermatitis, a chronic inflammatory skin disease, has also been found to be close to 1 million.
According to the National Health Insurance’s health insurance treatment data, by age, patients under the age of 9 accounted for 271,613 patients, accounting for 28.0% of the total. This was followed by 16.7% (161,771 people) in their 20s and 15.5% (150,837 people) in their teens. In particular, the prevalence of pediatric atopic dermatitis in Korea shows an increasing trend from 8.8% in 1995 to 12.7% in 2015.
It is a chronic inflammatory skin disease that begins in infancy and shows a natural course, with the highest prevalence in children and a gradual decrease with age. Most of them are alleviated after adolescence, but without proper treatment and management, they tend to progress to severe atopic dermatitis and continue into adulthood.
There are currently steroid ointments, antihistamines, biological agents, and JAK inhibitors for atopic dermatitis, and the development of compounds such as immunosuppressants or antibody therapeutics is currently making a breakthrough in treatment.
Representative biological agents include ‘Dupixent’ (ingredient name dupilumab) from Sanofi, France, which simultaneously inhibits interleukin-4 (IL-4) and interleukin-13 (IL-13), which cause symptoms of atopic dermatitis.
As an antibody treatment, ‘Adtralza’ (ingredient: tralokinumab) from Leo Pharma in Denmark, which inhibits interleukin (IL)-13, is emerging as a dark horse in the atopic dermatitis market.
JAK inhibitors that modulate multiple immune pathways are also emerging as new atopic dermatitis treatments. Representative drugs include US Pfizer’s ‘Civinco’ (ingredient name abrocitinib) and AbbVie’s ‘Rinvoq’ (ingredient name upadacitinib).
However, these drugs suffer from various side effects, high cost, and continuous recurrence. In particular, the treatment effect differs depending on the individual’s immune function, previous treatment experience, and aggravating factors.
Therefore, for the treatment of patients suffering from severe chronic atopic dermatitis, it is necessary to discover new treatment targets that can effectively control the inflammatory response caused by atopy.
Production of IP-10 and its mechanism of action in house dust mite-sensitive atopic dermatitis. Keratinocytes exposed to house dust mite antigens produce IP-10 and increase secretion. The secreted IP-10 diffuses into regional lymph nodes and induces the activation of transcription factors in undifferentiated Th0 cells, leading to their differentiation into Th2 cells. In addition, it stimulates inactive Th2 cells in the lesion area to activate Th2 cells that produce IL-4. Through this series of processes, an amplified Th2-response is induced.
◇Discovery of new immune factors that can effectively control inflammation caused by house dust mites
The cause of atopic dermatitis is too diverse, and the process is very complicated. The research team conducted a study by specifying atopic dermatitis caused by the house dust mite antigen, which accounts for about 70% of the prevalence of atopy, to ensure definitive research results.
House dust mites are known to be the most important causative antigen of atopic dermatitis, and children with atopic dermatitis have a high risk of being sensitized to inhaled allergens, and the Allergic March begins with more than 50% of asthma and more than 75% of rhinitis. do.
Although the positive rate of house dust mite in atopic patients reaches 68.8%, studies on specific mechanisms are lacking due to complex antigenicity.
In particular, keratinocytes secrete various inflammatory mediators and continuously interact with surrounding immune cells to induce aggravation or chronicity of the disease. Despite numerous studies, antigen-specific secretion from keratinocytes by house dust mites Discovery of the enemy factor and verification of its role in the immune activity of atopic dermatitis are very insufficient.
Accordingly, the research team confirmed that IP-10 (Interferon-γ-inducible protein-10, CXCL10) was secreted at the highest level among numerous factors secreted from keratinocytes stimulated with house dust mite antigens, and tried to verify its role.
As a result of the experiment, the expression level of IP-10 in atopic dermatitis lesions had a decisive effect on the representative clinical signs of atopy, such as skin thickening, erythema, and increased keratin accompanied by inflammation, and directly inhibited Th2-cell-mediated immunity, an important indicator of allergic diseases. It was confirmed that the adjustment of
◇Developing new drug candidates that effectively control IP-10, are less toxic and have excellent skin penetration
The key to this study is to identify the fact that IP-10 acts as an important malignant loop-inducing factor that exacerbates and makes atopic dermatitis chronic by activating lymphocytes infiltrating into the lesion area. Therefore, controlling the IP-10 factor makes it possible to develop a new concept of atopic dermatitis target treatment.
House dust mites activate several pathways at the same time due to the complexity of their antigens, so it is not easy to control the mechanism. Therefore, the results of this study clarify the importance of IP-10 as a factor that shows a specific response to house dust mites despite simultaneous antigen stimulation, and identify specific regulatory pathways and their roles, thereby providing an advanced solution for atopic treatment. It is an evaluation that suggested
Professor Sang-Hyun Kim said, “This research result is that we have found an immunoregulatory factor that regulates the interaction between skin epithelial cells and various immune cells that exacerbate or chronicate atopic dermatitis.” Nano-drug conjugates are being synthesized to improve the physical properties of drugs while developing new drug candidates with low skin penetration and excellent skin penetration. It is expected that it will be applicable to the treatment of patients with severe and intractable atopic dermatitis in the future.”
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