“Children of mothers with lupus have a higher incidence of autism and learning disabilities, and therefore we investigate the impact of paragenetic inheritance on the neuropsychiatric fitness of the offspring.”
Can the maternal immune state ‘imprint’ on a fetus from the very beginning and influence the offspring throughout its lifetime? That is an urgent question for associate professor, PhD Søren Degn, born 1981, whose research group explores autoimmunity and tolerance.
Organized around Søren Degn’s Lundbeckfonden Fellowship, their studies in mice indicate that genetically normal offspring of autoimmune mothers have an abnormally activated immune system – unlike genetically normal offspring of autoimmune fathers. This ‘paragenetic inheritance’ suggests that maternal immune factors, whether they be antibodies, cytokines or cells, significantly influence the developing fetus.
“Children of mothers with lupus have a higher incidence of autism and learning disabilities, and therefore we investigate the impact of paragenetic inheritance on the neuropsychiatric fitness of the offspring,” Søren Degn says.
He believes this is an entirely new mode of inheritance, based in the immune system’s ability to learn and remember. Basically, Søren Degn suggests that acquired or trained lymphocyte repertoires represent a novel mode of transfer of heritable information.
Søren Degn has already achieved remarkable results. For example, he elucidated the molecular underpinnings of a process called epitope spreading, whereby an autoimmune reaction spreads in the body - like ripples in water. By showing precisely what happens at a cellular level, Søren Degn hopes to help develop targeted medicine to curb this negative immune spiral.
“Years before an autoimmune patient presents in the doctor’s office, her body has produced antibodies to a few defined autoantigens - components of her own cells. The process expands, and over time, the patient reacts to a breadth of autoantigens. Cut to the chase, this is what drives disease development and causes worsening of symptoms,” Søren Degn explains.
Søren Degn’s work can definitely be categorized as basic research. Nonetheless the overarching theme of tolerance vs. autoimmunity relates directly to the most pressing challenges to human health on a global scale.
“Children of mothers with lupus have a higher incidence of autism and learning disabilities, and therefore we investigate the impact of paragenetic inheritance on the neuropsychiatric fitness of the offspring.”