Pathogenic particles in the blood identified with a new technique

By on January 11, 2022 0

They take a blood sample and soon after, researchers can find signs that indicate whether a person is about to develop lupus disease – or is already sick. The revolutionary technique can be an important tool in diagnosing more autoimmune diseases.

Autoimmune diseases – that is, diseases where our own immune system damages the body – do develop, but we know little about what triggers them.

Researchers are now one step closer to finding an explanation. Using a new technique, researchers from Aarhus University have successfully identified the particles in the blood that determine the development of autoimmune diseases. They found that patients with the autoimmune disease of systemic lupus erythematosus (also called SLE or lupus) form a previously unknown type of protein particle in the blood, and this particle is so large that it enters the blood. the vascular wall where it causes damage. . The disease is potentially fatal and can cause blood clots and inflammation of joints and organs, for example.

Particles measured in nanometers

“We can see that the patients have a high proportion of large particles in their blood. Due to their size, they are distributed right at the edge of the blood vessel, where they can potentially end up in the vessel wall and create inflammation, ”says postdoctoral fellow Kristian Juul-Madsen of the University of Biomedicine Department. Aarhus.

He is the lead author of a recently published study that describes how researchers were able to use a new technique that allowed them to track specific protein particles in a patient’s blood sample and measure their size in nanometers. In doing so, it becomes clear that the scope and structure of the particles are crucial for the development of the disease.

Thomas Vorup Jensen and Kristian Juul Madsen

“We can follow the process on a screen and this led us to discover that patients with lupus have a much higher concentration of very large particles in their blood,” says post.doc Kristian Juul-Madsen (right) . Credit: Simon Byrial Fischel

“We connect the protein particles with small metal particles, which emit a strong fluorescence when illuminated by a laser. We can follow the process on a screen and this led us to discover that patients with lupus have a much higher concentration of very large particles, ”says Kristian Juul-Madsen.

“The technique identifies something rare but absolutely crucial for the development of the disease in patients with lupus. We imagine that there is a critical level below which you have to stay to avoid disease, ”he says.

Early diagnosis of the disease is important because treatment can reduce symptoms and prevent organ damage. Therefore, it is also extremely interesting in a clinical context for researchers to be able to take a blood sample and already have five minutes later an answer as to whether the patient is on the way to developing lupus or is already ill. .

Blood samples already taken

The study of lupus patients was established in collaboration with the Rheumatology Department at Aarhus University Hospital, where Principal Registrar Anne Margrethe Troldborg, who is also Assistant Professor in the Department of Biomedicine, brought together one of the largest lupus cohorts in Denmark. . His work with lupus patients gave researchers a head start, as blood samples from patients and control groups had already been collected – work that would otherwise take several years.

The new technique is expected to be available as a diagnostic tool in the clinic at Aarhus University Hospital within 5 to 10 years.

Patented technology

The discovery of pathogenic particles provides a better understanding of why the disease occurs. In the longer term, this will hopefully help prevent the development of lupus and improve researchers’ knowledge of hereditary and other factors. Together with Professor Thomas Vorup-Jensen, Kristian Juul Madsen patented the technology, which they call NIP-Q (Nanoscale Immunoactive Protein Quantification).

Initially, the patent only applies to analyzes of the protein that occur in patients with lupus, but the research team expects the technique can also be used to detect other inflammatory diseases. such as rheumatoid arthritis.

“In the research community, the focus is on how inflammatory diseases lead to the release of DNA in the blood, and that the process can activate the immune system to some extent. But we got a whole new idea by producing an analysis of the size of blood components. It’s deeply fascinating to see how we can use the new technique to find a correlation between particle size and immune response, ”says Thomas Vorup-Jensen.

He explains that it is often difficult for doctors to make an accurate diagnosis and follow the course of an autoimmune disease. This can make it difficult to make decisions about drugs and how to measure their effects.

“Nonetheless, the costs of autoimmune diseases continue to rise, both because of their increasing incidence and in parallel with the development of expensive new drugs. Better measurement methods are therefore necessary in order to be able to regulate treatments in a responsible manner both in terms of health and health economics ”, explains Thomas Vorup-Jensen.

Reference: “Characterization of DNA-protein complexes by monitoring analysis of nanoparticles and their association with systemic lupus erythematosus” by Kristian Juul-Madsen, Anne Troldborg, Thomas R. Wittenborn, Mads G. Axelsen, Huaying Zhao, Lasse H. Klausen , Stefanie Luecke, Søren R. Paludan, Kristian Stengaard-Pedersen, Mingdong Dong, Holger J. Møller, Steffen Thiel, Henrik Jensen, Peter Schuck, Duncan S. Sutherland, Søren E. Degn and Thomas Vorup-Jensen, July 27, 2021, Proceedings of the National Academy of Sciences.
DOI: 10.1073 / pnas.2106647118

Research results – more information:

  • The study is an experimental analysis of the structure of proteins, both in pure form and in comparison with blood samples taken from patients with lupus. Based on the experimental values ​​of protein size (hydrodynamic radius), theoretical calculations were made on the distribution of protein particles in blood according to known vessel diameters and blood pressure. The study also includes experiments on mice.
  • The study was conducted in collaboration between researchers from Aarhus University, Aarhus University Hospital, University of Copenhagen and National Institutes of Health, Maryland, USA.
  • The study is supported by the Aarhus University Research Foundation, the Novo Nordisk Foundation and the Lundbeck Foundation.
  • The research group has applied for a patent for the invention with Aarhus University as the owner.