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Susceptibility to rheumatism unravelled

Researchers at the Leiden University Medical Centre (LUMC) have clarified the mechanism behind the susceptibility to rheumatism. The study explains why some people are at an increased risk and, to the contrary, why others are protected against it.

 

Rheumatoid arthritis is a chronic inflammation of the mucous membrane in the joints. Not everybody is equally susceptible to the development of rheumatism. The study at the LUMC explains this.

In many viruses and bacteria, for example the flu virus, a protein occurs that is very similar to a piece of the human protein vinculin. This protein also occurs in the joints. When the immune system wants to attack the pathogen, the vinculin in the joints can also be attacked, resulting in an inflammation. This is called a cross reaction. However, this reaction does not occur in everyone.

It has been known for some time that people with certain variants of HLA antigens have an increased risk of rheumatoid arthritis. Other variants protect the carrier of this.

HLA antigens present pieces of protein to the outside of the cell, so that immune cells can start an immune response. The HLA antigens of people who are protected against rheumatism contain pieces of protein that occur in both vinculin and in the pathogens. According to the study, this resemblance is responsible for no immune cells being produced against vinculin and therefore rheumatoid arthritis occurring in the joints.

However, the question remains why rheumatoid arthritis is usually doesn’t cause problems throughout the entire body until a later stage, because vinculin also occurs in other places in the body.

“It may be the case that cells in joints break down earlier due to friction. Vinculin is then released in large amounts and when you then have immune cells against this protein, your joints can be attacked”, said the researchers. This hypothesis will be investigated further in the future.

Sources

  1.       Heemst J. van et al., Crossreactivity to vinculin and microbes provides a molecular basis for HLA-based protection against rheumatoid arthritis, Nat Commun. 2015 May 5;6:6681
  2.       https://www.lumc.nl/over-het-lumc/nieuws/2015/mei/Mechanisme-achter-gevoeligheid-voor-reuma-ontrafeld/
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