PAX5 mutations are the cause of both the immunological and neurological problems
A collaborative effort led by dr. A. Badura and prof. Dr. Meinrad Busslinger, PAX5-specialized immunologists from the Research Institute of Molecular Pathology in Vienna highlighted the importance of the PAX5 gene. The team focused on a young patient, whose body produced too few antibodies, who had a mutation in both copies of the so-called PAX5 gene. One copy did not work at all and the other copy worked less well. PAX5 plays a role in the development of B cells, the cells that produce antibodies. This patient was also challenged with neurological problems: autism, a developmental delay and motor deficits. Autism had previously been linked to a single mutation in the PAX5 gene, but whether this was a causal link remained unclear. The main question in this case was: Are PAX5 mutations the cause of both the immunological and neurological problems?
In the article published last week in the Journal of Experimental Medicine the team of scientists and clinicians led by Fabian Kaiser, an immunologist and pediatrician in training at Erasmus MC set up to answer this question. By combining human and animal research the team found a link between the behavioral deficits and abnormal brain structure. Specifically, the mouse model showed abnormalities in the cerebellum and smaller deep brain structures called the substantia nigra and the ventral tegmental area were a lot smaller than normal. These abnormalities could also be seen on an MRI scan of the patient’s brain.
By combining the mouse model with the patient’s data, the scientists can now explain for the first time how a mutation in PAX5 leads to both autism and immune problems. For the individual patient, unfortunately, this does not immediately provide a different or new treatment. ‘That’s still years away. We are therefore extra grateful to him and his mother for being willing to cooperate with our research’, says dr. Badura.