(Press-News.org) WHAT:
A drug approved to treat certain autoimmune diseases and cancers successfully alleviated symptoms of a rare genetic syndrome called autoimmune polyendocrine syndrome type 1 (APS-1). Researchers identified the treatment based on their discovery that the syndrome is linked to elevated levels of interferon-gamma (IFN-gamma), a protein involved in immune system responses, providing new insights into the role of IFN-gamma in autoimmunity. The study, led by researchers at the National Institutes of Health’s National Institute of Allergy and Infectious Diseases, was published today in the New England Journal of Medicine.
In a three-stage study, conducted in mice and people, the researchers examined how APS-1 causes autoimmune disease. The syndrome is marked by dysfunction of multiple organs, usually beginning in childhood, and is fatal in more than 30% of cases. This inherited syndrome is caused by a deficiency in a gene that keeps the immune system’s T cells from attacking cells of the body, leading to autoimmunity; chronic yeast infections in the skin, nails, and mucous membranes; and insufficient production of hormones from endocrine organs, such as the adrenal glands. Symptoms include stomach irritation, liver inflammation, lung irritation, hair loss, loss of skin coloring, tissue damage, and organ failure.
In the first stage of this study, researchers led by scientists in NIAID’s Laboratory of Clinical Immunology and Microbiology examined the natural history of APS-1 in 110 adults and children. Blood and tissues were analyzed to compare gene and protein expression in people with and without APS-1. They found elevated IFN-gamma responses in the blood and tissues of people with APS-1, indicating that IFN-gamma may play an important role in the disease and providing a pathway to target for treatment.
In the second stage of the study, the scientists examined mice with the same gene deficiency that causes APS-1 in people, finding that the animals also experienced autoimmune tissue damage and elevated IFN-gamma levels. Mice also deficient in the gene for IFN-gamma did not have autoimmune tissue damage, which showed a direct link between IFN-gamma and APS-1 symptoms. With this understanding, the researchers looked for a drug that could be used to lower IFN-gamma activity in people. They selected ruxolitinib, a Janus kinase inhibitor, because it acts by shutting down the pathway driven by IFN-gamma. When ruxolitinib was administered to the mice with the gene deficiency that causes APS-1, IFN-gamma responses were normalized and T cells were prevented from infiltrating tissues and damaging organs. These results showed that ruxolitinib could alleviate effects of the gene deficiency, suggesting that it could be effective for treatment of APS-1 in people.
The researchers administered ruxolitinib, which was supplied by the NIH Clinical Center, to five people—two adults and three children—with APS-1 in the third stage of the study. The dosing and regimens were tailored to the individuals, and the treatments were continued for over a year. The drug was safe and tolerated well, and improvement in symptoms was seen in all study participants. Blood and tissue analyses revealed decreased production of IFN-gamma from T cells, as well as normalized levels of IFN-gamma in the blood. Many APS-1-related symptoms were reduced, including hair loss, oral yeast infections, stomach and bowel irritation, hives, and thyroid inflammation.
The results revealed that normalizing IFN-gamma levels using ruxolitinib could reduce the damaging effects of APS-1 in people. The scientists note that a study with a larger and more diverse group of patients is needed to determine whether ruxolitinib and similar drugs are suitable treatments for individuals with APS-1. They write that understanding the role of IFN-gamma in autoimmunity may lead to the development of treatments for related diseases. This research highlights the importance of finding the causes of and treatments for rare diseases.
Editorial note: APS-1 is also known as polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) in the literature.
REFERENCE:
V Oikonomou et al. The role of interferon-gamma in Autoimmune Polyendocrine Syndrome Type 1. New England Journal of Medicine DOI: 10.1056/NEJMoa2312665 (2024).
WHO:
Michail S. Lionakis, M.D., Sc.D., chief of NIAID’s Fungal Pathogenesis Section and deputy chief of NIAID’s Laboratory of Clinical Immunology and Microbiology, is available to discuss this research.
CONTACT:
To schedule interviews, please contact NIAID News & Science Writing Branch, 301-402-1663, niaidnews@niaid.nih.gov.
NIAID conducts and supports research—at NIH, throughout the United States, and worldwide—to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID website.
About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov/.
NIH...Turning Discovery Into Health®
END
INDIANAPOLIS -- Many adults with diabetes and the associated complication of peripheral neuropathy, which can be painful as well as harmful, are often prescribed drugs at doses and for durations that could impose an increased risk of cognitive impairment.
A new study, led by Regenstrief Institute and Purdue University College of Pharmacy Research Scientist Noll Campbell, PharmD, M.S., is one of the first explorations of prescribing patterns of tricyclic antidepressants for treatment of diabetic peripheral neuropathy at healthcare facilities predominantly serving diverse populations of low socioeconomic status.
With a study population of adults 18 years and older that ...
New materials for producing oxygen may challenge traditional production methods. This is exciting news, because pure oxygen is in demand from many areas in industry and medicine.
“We have identified materials that can store and release pure oxygen much faster and at much lower temperatures than known materials currently used for this purpose,” says Professor Sverre Magnus Selbach at the Norwegian University of Science and Technology (NTNU’s) Department of Materials Science and Engineering.
Oxygen is an element, so it ...
While threats and violence against pre-K to 12th-grade teachers and other school personnel in the United States declined during the pandemic, after the restrictions were lifted, incidents rebounded to levels equal to or exceeding those prior to the pandemic, according to research published by the American Psychological Association.
As a result, the percentage of teachers expressing intentions to resign or transfer rose from 49% during the pandemic to 57% afterward, the researchers found.
“Aggression and violence against educators and school personnel are major concerns that affect the well-being of school personnel and the ...
DARIEN, IL – A new study to be presented at the SLEEP 2024 annual meeting found a distinct relationship between sleep duration, social media usage, and brain activation across brain regions that are key for executive control and reward processing.
Results show a correlation between shorter sleep duration and greater social media usage in teens. The analysis points to involvement of areas within the frontolimbic brain regions, such as the inferior and middle frontal gyri, in these relationships. ...
DARIEN, IL – A new study to be presented at the SLEEP 2024 annual meeting found that better sleep health was associated with lower levels of loneliness, and this association was stronger among younger adults.
Results indicate that better sleep health was associated with significantly lower total loneliness, emotional loneliness and social loneliness. While better sleep health was associated with lower total and emotional loneliness across ages, this association was stronger for younger adults. However, age did not moderate the association ...
WHAT:
Using a combination of cutting-edge immunologic technologies, researchers have successfully stimulated animals’ immune systems to induce rare precursor B cells of a class of HIV broadly neutralizing antibodies (bNAbs). The findings, published today in Nature Immunology, are an encouraging, incremental step in developing a preventive HIV vaccine.
HIV is genetically diverse making the virus difficult to target with a vaccine, but bNAbs may overcome that hurdle because they bind to parts of the virus that remain constant even when it mutates. ...
DARIEN, IL – A new study to be presented at the SLEEP 2024 annual meeting demonstrates that when individuals with obstructive sleep apnea use their positive airway pressure machine more regularly, it benefits their relationship with their partner.
Results show that greater adherence to PAP therapy was associated with higher levels of relationship satisfaction and lower levels of relationship conflict. Higher sleep efficiency among patients also was associated with higher levels of relationship satisfaction as reported by both the patient and their partner.
“Recognizing that sleep ...
New research from the University of Lausanne reveals that both the excess and the deficiency of a single protein can lead to severe intellectual deficiencies. The discovery offers critical insights for early diagnosis of a rare developmental disorder.
A team of scientists led by Alexandre Reymond, an expert in human genetics at the Center for Integrative Genomics (CIG) and professor at the Faculty of Biology and Medicine (FBM) of the University of Lausanne (UNIL), presents a major step forward in the detection of a rare genetic disease. For ...
Boston – Four teams of Dana-Farber Cancer Institute investigators have found that people experience discrimination and bias in different ways and in more realms of cancer care than previously understood. The findings, in different studies, suggest that oncology professionals and the systems they work in have more work to do to adapt to the realities of increasing diversity and inclusion, not only in the patient population but also in the oncology workforce. The research teams will present their findings at the 2024 Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago. ASCO is the world’s largest clinical cancer ...
ROCHESTER, Minnesota — Early detection improves treatment outcomes for endometrial and ovarian cancers, yet far too often women are diagnosed in advanced stages of these diseases. Unlike many other cancers, there are no standard screenings for early detection of endometrial and ovarian cancers. The incidence rate for endometrial cancer is expected to rise, driven by environmental factors, obesity and diabetes.
Marina Walther-Antonio, Ph.D., and colleagues at Mayo Clinic's Center for Individualized Medicine are on a mission to catch these cancers early.
Their research dives deep into the microbiome, a community of ...
