Major step towards personalised medicine against hereditary autoimmune deficiency

August 14, 2014

Researchers at Karolinska Institutet in Sweden have found a method to repair the gene mutation causing agammaglobulinemia, an autoimmune deficiency disease that almost exclusively affects boys and in which the body lacks the ability to produce immunoglobulins (gamma globulin). The disease is characterised by recurring bacterial infections, mainly in the respiratory system, and persons who suffer from the illness currently need life-long gamma globulin treatment.

"Although there is a lot of research left to be done, the findings indicate that we may be able to treat some patients in the future," says Edvard Smith, Professor at the Department of Laboratory Medicine at Karolinska Institutet and one of the researchers behind the study that is presented in the Journal of Clinical Investigation.

Agammaglobulinemia is a rare, hereditary disease that is caused by a mutation which results in a lack of the enzyme BTK. BTK plays an important role in the signalling of white blood cells and thus in developing and maintaining an effective autoimmune system. In the new study, the researchers show that it is possible to repair faulty RNA and recreate BTK in lymphocytes, . The new study emanates from the same research group at Karolinska Institutet that previously identified the predisposition for sex-linked agammaglobulinemia (XLA).

It is previously known that synthetic building blocks in our genetic make-up (known as oligonucleotides) can modify the RNA and recreate truncated forms of the protein that is missing in severe muscular dystrophy. The new study shows that it is possible to experimentally correct the defect and recreate an intact BTZ enzyme for a Swedish family with XLA. The therapy has been customised for this particular mutation and is thereby a genuine example of "personalised medicine". The researchers utilised molecular biological methods and created a mouse which carries the gene in question. The mice also lacked enzymes of their own, as their genes were inactivated.

"We have been able to show how synthetic oligonucleotides can correct RNA both in patient cells in a test tube, and in living animals," says Edvard Smith.

The number of new cases of agammaglobulinemia is estimated at 6 in one million births, which means that there is roughly one boy born with the disease in Sweden every other year. BTK has received renewed attention as it has been discovered that the protein also plays an important role in various types of blood cancer that have their origin in immune cells. A new medicine that blocks the function of the BTK enzyme was recently approved for the treatment of leukaemia and lymphoma in the USA.

The study has been financed using funds from the Swedish Cancer Society, the Swedish Research Council and Stockholm County Council (ALF), among others.

Explore further: Scientists discover 'switch' to boost anti-viral response to fight infectious diseases

More information: 'Splice-correcting oligonucleotides restore BTK function in X-linked agammaglobulinemia model' Burcu Bestas, Pedro M.D. Moreno, K. Emelie M. Blomberg, Dara K. Mohammad, Amer F. Saleh, Tolga Sutlu, Joel Z. Nordin, Peter Guterstam, Manuela O. Gustafsson, Shabnam Kharazi, Barbara Piatosa, Thomas C. Roberts, Mark A. Behlke, Matthew J.A. Wood, Michael J. Gait, Karin E. Lundin, Samir EL Andaloussi, Robert Månsson, Anna Berglöf, Jesper Wengel, och C.I. Edvard Smith, Journal of Clinical Investigation, 8 August 2014, DOI: 10.1172/JCI76175

Related Stories

Study confirms target of potent chronic leukemia drug

December 19, 2013

A new study led by researchers at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James) helps confirm that a molecule targeted ...

Recommended for you

Snapshot turns T cell immunology on its head

October 6, 2015

Challenging a universally accepted, longstanding consensus in the field of immunity requires hard evidence. New research from the Australian Research Council Centre of excellence in advanced Molecular imaging has shown the ...

Four gut bacteria decrease asthma risk in infants

September 30, 2015

New research by scientists at UBC and BC Children's Hospital finds that infants can be protected from getting asthma if they acquire four types of gut bacteria by three months of age. More than 300 families from across Canada ...

Flu infection reveals many paths to immune response

September 28, 2015

A new study of influenza infection in an animal model broadens understanding of how the immune system responds to flu virus, showing that the process is more dynamic than usually described, engaging a broader array of biological ...

Immune cells may help fight against obesity

September 15, 2015

While a healthy lifestyle and "good genes" are known to help prevent obesity, new research published on September 15 in Immunity indicates that certain aspects of the immune system may also play an important role. In the ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.