) Researchers found that the syndrome is connected to high levels of interferon-gamma (IFN-gamma), a protein involved in immune system responses. This discovery offers new understanding of the role of IFN-gamma in autoimmunity.Researchers have found a new treatment for a syndrome that is connected to high levels of interferon-gamma (IFN-gamma), a protein that plays a role in the immune system. This discovery provides new understanding about how IFN-gamma is involved in autoimmune diseases. The study, led by researchers at the National Institute of Allergy and Infectious Diseases, was published in the New England Journal of Medicine.
The researchers conducted a three-stage study in mice and humans to understand how APS-1 causes autoimmune disease. This syndrome is characterized by the malfunction of multiple organs.The inherited syndrome, which often starts in childhood and is deadly in over 30% of cases, affects various organs. It is caused by a gene deficiency that prevents the immune system’s T cells from attacking the body’s cells, leading to autoimmunity. This results in chronic yeast infections in the skin, nails, and mucous membranes, as well as inadequate production of hormones from endocrine organs like the adrenal glands. Symptoms of the syndrome include stomach irritation, liver inflammation, lung irritation, hair loss, loss of skin coloring, tissue damage, and organ failure.
The natural history of APS-1 was studied in 110 adults and children by Immunology and Microbiology experts. The study involved analyzing blood and tissues to compare gene and protein expression in individuals with APS-1 and those without. The results showed elevated IFN-gamma responses in the blood and tissues of people with APS-1, indicating the potential importance of IFN-gamma in the disease and suggesting a possible target for treatment.
In the second part of the study, researchers examined mice with the same gene deficiency that causes APS-1 in humans. The mice also showed autoimmune tissue damage and increased levels of IFN-gamma. Additionally, mice deficient in The gene for IFN-gamma was found to be linked to APS-1 symptoms, as mice with the gene deficiency did not experience autoimmune tissue damage. With this knowledge, researchers set out to find a drug that could reduce IFN-gamma activity in humans. They chose ruxolitinib, a Janus kinase inhibitor, because it can shut down the pathway driven by IFN-gamma. When ruxolitinib was given to the mice with the gene deficiency, it normalized IFN-gamma responses and prevented T cells from infiltrating tissues and causing organ damage. These findings suggested that ruxolitinib could help alleviate the effects of the gene deficiency.The study suggests that ruxolitinib could be an effective treatment for APS-1 in individuals. During the third stage of the study, researchers provided ruxolitinib from the NIH Clinical Center to five participants – two adults and three children. The dosages and schedules were customized for each person, and the treatments lasted for over a year. The drug was well-tolerated and safe, and all participants showed improvement in their symptoms. Analysis of blood and tissue revealed a decrease in the production of IFN-gamma from T cells, and normalized levels of IFN-gamma in the blood. Many symptoms associated with APS-1 were reduced., such as hair loss, oral yeast infections, stomach and bowel irritation, hives, and thyroid inflammation.
The study found that by normalizing IFN-gamma levels with ruxolitinib, the damaging effects of APS-1 could potentially be reduced in individuals. The researchers emphasize the need for a larger and more diverse patient population to determine the effectiveness of ruxolitinib and similar drugs as treatments for APS-1. They suggest that understanding the role of IFN-gamma in autoimmunity could lead to the development of treatments for related diseases. This research underscores the significance of identifying the causes and potential treatments for APS-1 and other related conditions.for rare diseases.
