Preventing tissue damage by inhibiting neutrophils in autoimmunity
Neutrophils are abundant cells of the immune system. Their main function is to destroy invading pathogens. However, excess activation can cause tissue damage and chronic inflammation. The main research question was therefore: ‘Are neutrophils a suitable target to reduce tissue damage in chronic inflammation and autoimmunity’? The van Egmond lab of the VUmc has great expertise with studying neutrophil activation. Bioceros has expressed its interest in this research question, because it can open up ample opportunities for future development of therapeutics. Both parties have joined forces to investigate whether targeting neutrophils will resolve existing inflammation and decrease disease.
Neutrophils are found in many chronic inflammatory or autoimmune diseases like rheumatoid arthritis, inflammatory bowel disease (IBD), and asthma, but their potential detrimental role is mostly overlooked. Many of these diseases are prevalent in Western society, and incidence is increasing due to our modern life style. These diseases generally manifest at early age, and have a great negative impact on patients, their social network, employers and the society. Cure is not yet possible and the disease last a life time.
They hypothesized that neutrophils induce severe tissue damage in the abovementioned diseases, hereby seriously aggravating illness. In this project they investigated neutrophil contribution in preclinical skin blistering and arthritis models, and tested new anti-FcRI monoclonal antibodies to inhibit neutrophils as proof of principle. Finding new ways to prevent tissue damage may improve health and well-being of many patients suffering from the abovementioned autoimmune diseases.
In this project they established that neutrophils are responsible for serious damage in blistering diseases if IgA autoantibodies are present. Similarly, FcαRI transgenic mice developed symptoms of joint inflammation in a collagen induced arthritis (CIA) model, supporting that IgA-FcαRI interactions play a role in disease activity. Moreover, this project demonstrated that the new anti-CD89 mAbs developed and produced by Polpharma inhibited IgA-induced neutrophil activation, like phagocytosis, NET-release and migration. Importantly, the lead anti-CD89 mAb clone 10E7 reduced anti-autoantigen IgA-induced neutrophil influx in the in vivo LABD blistering model. They are currently investigating whether this also holds true for the CIA model. The lead clone 10E7 will be further developed for clinical application.
