New gene defect discovery helps to unlock the mystery of severe infectious mononucleosis

Almost all Finns suffer from symptomatic or asymptomatic “kissing disease”, or infectious mononucleosis (IM), at a young age, which is an infection caused by the Epstein-Barr virus (EBV). A small part of the patients requires hospital care. 

About 95 per cent of Finns are infected with the Epstein-Barr virus, which spreads through saliva. Most are exposed to the virus as a child, either without symptoms or with infectious mononucleosis as the only symptom. The symptoms of severe infectious mononucleosis are usually fever and severely swollen lymph nodes and spleen. Symptoms requiring hospital care include severe inflammatory symptoms, severe lymphatic tissue hyperplasia (overgrowth), decline in general condition and rupture of the spleen. 

New Finnish gene defect discovered

A new gene defect was discovered in the Finnish population, which, if inherited from both parents, may cause severe infectious mononucleosis but also help you cope with it. 

"This is a new hereditary disease in Finland, and around 300 Finns have it. One of its manifestations is severe infectious mononucleosis, which eventually heals on its own", says Chief Physician Mikko Seppänen from HUS Children and Adolescents and the University of Helsinki. 

The study published in the prestigious science journal Nature was carried out in international cooperation, which also included one of the principal researchers of the FinnGen project, Mark Daly from the University of Helsinki. 

Hope for new treatments for serious diseases

Some people with severe infectious mononucleosis are later diagnosed with other diseases associated with the Epstein-Barr virus, such as lymphatic tissue hyperplasia, which may lead to lymph node cancers or severe lymph node inflammation. 

Everyone infected with the EBV carry the virus for the rest of their life. The study revealed that the gene defect prevented the gene from functioning, making it unable to communicate in its communication pathway. This led to a sudden inflammation with more symptoms than usual. At the same time, the gene defect surprisingly appeared to protect against uncontrolled general inflammation and life-threatening lymphatic tissue growth leading to tumor diseases. These can appear quickly in many hereditary immune deficiencies, or even decades later in drug-induced immune deficiencies. In other words, a functional gene was required for the uncontrolled overgrowth of lymphatic tissue.

"In the future, we are interested in whether the progression of lymphatic hyperplasia could be prevented by a treatment that silences the communication pathway found. If it works, we might be able to stop the progression of many of the most difficult blood cancers and lymph node tumors," Mikko Seppänen says.

The study monitored the patients for only a few years, so preparations for a new study have already begun. The aim is to find out whether Finnish biobanks and the children treated for infectious mononucleosis at the New Children's Hospital have this genetic defect. 

"Biobank research can quickly determine whether these children should be prepared for the risk of an immune disease later in life. At the same time, we will find out the whole spectrum of the disease," says Seppänen.

Finnish biobanks and FinnGen project played a key role in the discovery

The study was launched at the Institute Imagine and Université Paris Cité, which specialize in genetic diseases in France, where three French children with severe infectious mononucleosis were examined for rare genetic defects. Severe mononucleosis infections are very rare in Central and Southern Europe.

Through HUS, the French contacted the FinnGen project, which covers the whole of Finland and contains genome and health register data for more than 540,000 Finns. An analysis carried out by FinnGen confirmed that the gene defect may cause severe infectious mononucleosis. 

Kymenlaakso, Helsinki region and Savo have the highest number of carriers of the Finnish gene defect. The gene defect is approximately 50 times more common in Finns than in other populations. 

Link to research article: 
Role of IL-27 in Epstein–Barr virus infection revealed by IL-27RA deficiency