New ways of diagnosing rare diseases

Congenital defects may damage the immune system. Without the right treatment the consequences may be fatal. The aim of Yenan Bryceson’s research is to find mutations that cause these rare diseases. He has developed a blood test that can be used to screen newborn infants.

Yenan Bryceson


Wallenberg Academy Fellow 2014

Karolinska Institutet

Research field:
Mapping the effect of genetic mutations on the function of two types of white blood cells: cytotoxic T-cells and natural killer cells (NK-cells).

Each year two or three children in Sweden are born with the rare
disease HLH – hemophagocytic lymphohistiocytosis. Symptoms are normally fever, enlargement of the liver and spleen, and a decline in the number of red blood cells. Untreated, HLH is usually fatal.

“Serious congenital diseases of this kind can often be treated, but it is essential they be diagnosed as early as possible,” Yenan says. He is researching into primary immune deficiencies.

His research concerns genetic defects – mutations – in a class of white blood cells in the immune system that are capable of killing other cells. The aim is to learn more about how these mutations affect immune system cells, and cause disease. Yenan and his team have also developed a new blood test that can be used to screen newborn infants for HLH.

“In 2012, thanks to a combination of our knowledge of immunology and close collaboration with geneticists, we found mutations to explain HLH, and were then able to develop the test. It is enormously satisfying to see such tangible benefits from research.”

The plan is to soon include the test in the PKU (phenylketonuria) test, in which a blood sample is taken from all newborn babies in Sweden to find congenital diseases for which early treatment is essential.

Samples from the whole world

The immune system cells that Yenan is studying – natural killer cells and cytotoxic T-cells – normally play a key role in regulating infected cells and fighting cancer. They also regulate the activity of other cells in the immune system.

“Serious immune deficiencies may be caused by defects in various parts of the immune system. We are researching into a cause of immune deficiency,” Yenan explains.

“The support given by the Foundation will enable us to carry out the most ambitious elements of our research. We will be able to commit to riskier projects. The grant really does improve our prospects of keeping up with the rapid international developments in this field.”

In the laboratory at the Center for Infectious Medicine at Karolinska Institutet in Huddinge, south of Stockholm, Yenan and his team are studying a number of unusual diseases. Using advanced techniques, including flow cytometry, they are examining the immune cells in blood from patients, their siblings and parents. They are collaborating with departments and clinics at Astrid Lindgren Children’s Hospital and many other hospitals throughout the world.

“Most samples are delivered by express mail, but entire families sometimes travel to Huddinge so that blood samples can be taken on the spot.”

It is essential to examine cells in good condition that have not had too far to travel. The research team has also developed a new cellular technique for diagnosing rare diseases for use at clinics around the world.

“This is no routine test; it is advanced immune diagnostics: taking blood samples, cleaning out cells, and checking their function,” he explains.

Much to be understood

Yenan has always been fascinated by cells. He grew up in East Africa and Norway, and studied molecular biology at Oslo University. His doctoral studies were mostly conducted in the U.S. at the National Institute of Health, and also at the Center for Infectious Medicine, where he is now building up his research team. He is also adjunct professor at Bergen University in Norway.

“Immunology is a very exciting field. In the U.S. I began studying lymphocytes, i.e. white blood cells, and human immunology, and realized there is still a great deal we do not understand about the human immune system.”

Thanks to funding from the Knut and Alice Wallenberg Foundation, Yenan has now begun to study in detail how cytotoxic T-cells and natural killer cells work. He wants to better understand the structure of the cell nuclei, and the part of our DNA that is important in infections.

He hopes that greater knowledge of the inner workings of these cells will enable the team to find even more mutations that can be linked to disease.

“In many children who are very sick indeed we do not find any mutation. This makes diagnosis and treatment more difficult. Mutation may be absent because much of our DNA is made up not of genes, but of regulatory sequences that we do not yet fully understand. We want to know more about what governs these processes.”

New cancer treatment

Yenan points out that although the research team is mainly studying individuals with mutations in specific genes, their work is shedding new light on the immune system, which may also aid our understanding of other diseases.

“We are finding new cell types that also play a central role in cancer treatment. We are working with cancer researchers to understand how these cells can be used to treat cancer.”

The pace of development in the field of gene technology is incredibly rapid – something Yenan appreciates.

“Otherwise it would be boring. We are living in an age when genetics will change diagnostics and the treatment of many diseases, and we want to be at the forefront of developments.”

Text Susanne Rosén
Translation Maxwell Arding
Photo Magnus Bergström