Four new target molecules of potential significance for future personalized treatment of multiple sclerosis (MS) have been identified by researchers at the Karolinska Institute in Sweden.

“MS is an inflammatory disease of the central nervous system (CNS), in which pathological T cells, likely autoimmune, play a key role,” the researchers wrote in the journal Science Advances.

“Despite its central importance, the autoantigen repertoire remains largely uncharacterized. Using a novel in vitro antigen delivery method combined with the Human Protein Atlas library, we screened for T cell autoreactivity against 63 CNS-expressed proteins.”

“Existing MS treatments are quite indiscriminate in their effect on the immune system, which risks eventually causing complications, such as infections,” said Mattias Bronge, a PhD student in the research group of Hans Grönlund, PhD, in the department of clinical neuroscience, Karolinska Institutet. “Guiding future treatments more accurately towards the immune cells driving the disease can therefore lead to greater efficacy and fewer side effects.”

The novel method was developed to identify the T cells that react to certain target molecules, called autoantigens. The present study describes four new autoantigens that can be added to the handful of ones previously identified in MS.

“Our method makes it possible to present these autoantigens in a way that enables us to identify and subsequently disable the T cells that react to them,” said Grönlund.

“Once a patient’s individual autoantigen profile is identified, a treatment can be adapted accordingly,” explained Grönlund. “Most autoimmune diseases are driven by T cells and, if we can find a way to target them in diseases like MS, we can pave the way for more precise treatments with fewer side effects for other autoimmune diseases. Thanks to our long-standing collaboration with Professor Roland Martin at the University of Zürich, our method will be included in a Phase II clinical study that aims to ‘switch off’ the aggressive T cells which drive MS development and progression.”

“This represents one of the largest systematic efforts to date in the search for MS autoantigens, demonstrates the heterogeneity of autoreactive profiles, and highlights promising targets for future diagnostic tools and immunomodulatory therapies in MS,” concluded the researchers.