Promising drug for rare immunodeficiency syndrome


For the first time, there is now an opportunity to develop a broad treatment for patients with the rare and serious syndrome APS1. In a small pilot study, drugs that block the inflammatory signal have shown to work well for the patient group.

APS1 (autoimmune polyendocrine syndrome type 1) is a very rare and severe syndrome caused by mutations in a single gene, namely the AIRE (Autoimmune Regulator) gene. The protein coded by AIRE is crucial for ensuring that the immune system does not react against the body's own structures. Patients with APS1 develop a large number of autoimmune diseases simultaneously, which until now have been treated individually. 

This study presents a treatment that could potentially be effective for several of these diseases. The results, published in the New England Journal of Medicine, come from an international research collaboration in which researchers at the University of Gothenburg contributed with patients for the study, including one who participated in the pilot study for the drug. The group in Gothenburg also conducted some experimental analyses of patient material. 

Vanja Lundberg, postdoctoral researcher at the Institute of Medicine, and Olov Ekwall, professor of pediatric immunology at the Institute of Clinical Sciences.

Elegant study

Olov Ekwall, professor of pediatric immunology at the Institute of Clinical Sciences and senior physician at Sahlgrenska University Hospital, considers the study an elegant example of translational research: 

"Starting from a major clinical problem, studies were first conducted on patients, followed by mechanistic studies in a mouse model, and finally, the results were brought back to the patients again as a treatment study with very good results," says Olov Ekwall. 

Vanja Lundberg, a postdoctoral researcher in the group at the University of Gothenburg and resident physician at Queen Silvia's Children's Hospital, is also one of the co-authors of the study: 

"The primary benefit for patients is that it provides the opportunity to effectively treat several manifestations of the disease simultaneously with a drug that targets a common mechanism. In the study, we have seen good effects on nine different sub-diseases. Additionally, it is a drug that is already available," says Vanja Lundberg. 

Large cohort 

Thanks to the international collaboration, the researchers have managed to gather a large number of patients with this very rare congenital disease. The studies include thorough clinical characterization and experimental studies in patients, which enabled the identification of the signal molecule interferon gamma (IFNγ) as a key player in the inflammation in several of the affected organs. This mechanism has been verified in a mouse model of the disease (Aire knock-out mice), where the researchers also tested treating the mice by blocking the inflammatory signal with the drug ruxolitinib (a so-called JAK inhibitor) with good results. In a pilot study, ruxolitinib was also tested as a treatment for five patients, which yielded very good results on a large number of the inflammatory diseases and several of the affected organs. 

"Already, the treatment study has been expanded to more than 30 patients, and we continue to see very good treatment results," says Olov Ekwall. 

Article: The Role of Interferon-γ in Autoimmune Polyendocrine Syndrome Type 1;