New genetic clues could reveal why some people get meningitis

Scientists have uncovered genetic differences that could show who is most at risk of a potentially life-threatening infection.

The international research team identified gene variants that make people more susceptible to meningococcal disease – a serious bacterial infection that can be fatal.

The discovery has been published in The Journal of Allergy and Clinical Immunology.

Dr Evangelos Bellos from the University of Southampton is first author the paper.

The research lays the groundwork for new advances in the NIHR Southampton Biomedical Research Centre’s data, health and society theme. The researchers aim to move the insights toward improved treatments and outcomes for patients with the disease.

Understanding who gets the disease

Invasive meningococcal disease is a serious bacterial infection caused by Neisseria meningitidis. It can be life-threatening, particularly in babies, young children and teenagers.

The disease is spread by coughing and sneezing. It is the most common cause of bacterial meningitis, where the lining of the brain and spinal cord becomes infected and inflamed. It can also cause septicaemia, or blood poisoning, if the bloodstream is infected.

Yet only a small fraction of people who come into contact with Neisseria meningitidis actually get ill. The bacteria live harmlessly in the back of the nose and throat of about one in ten people.

The researchers aimed to find out why this type of bacteria causes such severe disease in some people, while others carry them harmlessly. To do this, they looked at people’s genetics.

Identifying gene variants

The researchers analysed the genetics of 229 patients with invasive meningococcal disease.

They were particularly interested in genes involved in the complement and coagulation pathways.

They compared this against the genetics of 275 patients with other invasive bacterial infections. This allowed them to identify gene variants only found in people with meningococcal disease.

Patients with meningococcal disease had many rare gene variants, including CFP and FCGR2A. Those with the most severe disease also had a variant of the gene SERPINE1.

This enabled the team to identify a key mechanism involved in the disease. This is known as complement-mediated thrombotic microangiopathy. This is a serious condition where blood clots form in the body's smallest blood vessels, blocking blood flow.

Dr Bellos, a Senior Lecturer in Genomic Informatics, said:

“These results shed new light on how Neisseria meningitidis causes meningococcal disease. They help to explain why the severity differs so much from person to person.

“We hope to build on this going forward. This will create a more complete picture of how and why this disease develops and who is most at risk. This could help to refine and tailor treatments for patients most at risk, so we can improve survival and long-term outcomes.”