ORCADES volunteers help understand sugar-coating of inflammation

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Genes influence our behaviour and characteristics. They are the DNA blueprints used to build proteins. These proteins are molecules which are essential for life. They perform many different functions in our body, including:

• Important structural roles (for example our hair is built from proteins called keratins)
• Defensive roles (e.g. antibodies that protect us from infections)
• Roles in transport (haemoglobin that carries oxygen in our blood cells)
• Roles in chemical reactions (for example enzymes that help us digest our food).

Glycans are sugars attached to the surface of a protein which can affect the function of the protein and how it attaches to other molecules. Immunoglobulins are specialised proteins that play the role of bodyguards in our immune system. Immunoglobulin G is the most plentiful of these antibodies.

When foreign substances (such as bacteria or viruses) enter our body, immunoglobulin G signals to the immune system that it should remove these. Based on the type of glycan attached to Immunoglobulin G, this signal can either increase or reduce inflammation response. Researchers used ORCADES volunteer data to search for genes that affect the addition of glycans to Immunoglobulin G (IgG).

Studying proteins without considering their glycosylation can be like trying to interpret colour from a black and white painting. This study helps reveal how altered glycosylation could affect inflammatory response in multiple diseases. Carrying a DNA variant that increases levels of pro-inflammatory IgG glycans could increase the chance of inflammation in these diseases

Lucija Klaric

The amounts of the glycan sugars attached to Immunoglobulin G were measured in more than 8000 people. Altogether, thirty-three different regions of DNA were found to be influencing the number of glycans on Immunoglobulin G. Using this information, the researchers showed new mechanisms regulating Immunoglobulin G glycosylation. They also showed that there are genetic variants influencing both Immunoglobulin G glycosylation and risk for inflammatory bowel disease, rheumatoid arthritis, asthma and Parkinson’s disease. 

Knowing which genes are involved in Immunoglobulin G glycosylation improves understanding of how the process affects disease risk. It was already known that glycans can be altered in various diseases, but it remains unclear exactly why this is.

This study, published in Science Advances, helps to shed light on the different molecules involved in these complex processes. This information can help in the development of new targets for drug treatments.