ERC grant for Maartje Huijbers to investigate role of unique antibody in autoimmune diseases

And so she did; with the reward now of receiving a prestigious grant (ERC Starting Grant) from the European Union to study the origins of IgG4. Her ultimate goal is to develop new treatments for IgG4-dominated autoimmune diseases.

The role of antibodies

Our immune system has multiple ways of attacking and clearing pathogens. One is the production of antibodies. Humans have five types of antibodies in their blood, the best known of which is IgG. IgG, in turn, has four subtypes: IgG1, IgG2, IgG3 and IgG4. In the case of an autoimmune disease, antibodies attack parts of one's own body.

A peculiar antibody

IgG4 is a very peculiar antibody. It is actually not very capable of putting the immune system to work. As a result, it was long considered an anti-inflammatory, benign antibody. More recently, it has been shown that IgG4 can have both good and bad affects, depending on the situation. For example, it can be a useful antibody in allergic patients because it inhibits the allergic response there.

On or off

But IgG4 can also be very pathogenic, according to studies by Huijbers and others. For example, in MuSK myasthenia gravis, a disease characterized by severe muscle weakness. Or in pemphigus, a disease characterized by blistering of the skin. Currently, 29 different autoimmune diseases are known in which IgG4 appears to play a role.

Huijbers: “However, we currently do not know why an IgG4 response occurs in one situation and not in another. So in this ERC project, I want to find out the 'recipe' for IgG4 responses and use this knowledge to specifically 'turn on' or 'turn off' IgG4 in different diseases.”

Developing new therapies

The study hopefully will lead to new therapies for these autoimmune diseases. It may also provide insights into the role of IgG4 in allergic responses, vaccination and in certain cancers, among others. Huijbers expects the first results to figure out the “recipe” in the next five years.