Study of over 6,000 people finds differences in natural defences leave some unable to defend against meningococcal bacteria - News Release

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1300 US Eastern time / 1800 London time
Sunday 8 August 2010

Genetic differences that make some people susceptible to developing meningococcal meningitis and septicaemia, and others naturally immune, are revealed in a new study of over 6,000 people, published today in Nature Genetics.

The research, led by Imperial College London and the Genome Institute of Singapore, is the largest ever genetic study of meningitis and septicaemia caused by meningococcal bacteria. It suggests that people who develop these diseases have innate differences in their natural defences that leave them unable to attack meningococcal bacteria successfully.

Although several different bacteria and viruses cause meningitis, meningococcal bacteria cause one of the most devastating forms of the disease - meningococcal meningitis, which is fatal in approximately one in ten cases. Meningococcal septicaemia is a type of blood poisoning that often accompanies this form of meningitis.

Meningococcal meningitis and septicaemia most commonly affect babies, young children, teenagers and young adults. The diseases are frightening because they can strike rapidly, with people becoming critically ill within hours.

There are vaccines available against some strains of meningococcal bacteria but not others. The researchers hope that their new findings will boost the development of effective vaccines to combat the group B strain of the bacteria, for which there is currently no vaccine. Every year, this strain causes thousands of deaths in children and adults across the world.

Most people carry the meningococcal bacteria in their throat intermittently during their lives without ever developing the disease. Prior to today's study, it has not been known why some people in the population develop meningococcal meningitis and septicaemia while others appear to be naturally immune to the bacteria.

Today's study compared the genetic makeup of 1,500 people who developed meningococcal meningitis, from the UK, Holland, Austria and Spain, with over 5,000 healthy controls from the Wellcome Trust Case Control Consortium. It was supported by the Wellcome Trust, Meningitis Research Foundation UK and the European Society for Paediatric Infectious Diseases.

Researchers looked at half a million common genetic variants scattered across each person's genome, and searched for differences between the patients with meningococcal disease and healthy controls. The results revealed that those who had developed meningococcal meningitis had genetic markers in a number of genes involved in attacking and killing invading bacteria.

Professor Michael Levin, from the Department of Paediatrics at Imperial College London, who led the international research effort, said: "Although most of us have carried the meningitis bacteria at some point, only around one in 40,000 people develop meningococcal meningitis. Our study set out to understand what causes this small group of people to become very ill whilst others remain immune. Our findings provide the strongest evidence so far that there are genetic factors that lead to people developing meningitis."

Dr Victoria Wright from the Department of Paediatrics at Imperial College London, who co-ordinated patient recruitment for the study across four European countries, added: "Meningococcal disease is a terrible illness as it strikes healthy children and adults suddenly, and can kill in a few hours. Improving our understanding of why some people get the disease and not others will help to identify those at risk and develop better vaccines. The success of the study was due to the willingness of patients and families to contribute their DNA for analysis, and it could not have been achieved without international collaboration."

The variations uncovered in the study were around the genes for Factor H and Factor H-related proteins. These proteins regulate a part of the body's immune system called the complement system, which recognises and kills invading bacteria.

Normally, Factor H and Factor H-related proteins ensure that the complement system does not cause excessive damage to the body's own cells. However, meningococcal bacteria can hijack the body's Factor H and use it to ensure that the body does not recognise the bacteria as foreign. The bacteria effectively use Factor H as a 'Trojan Horse,' enabling them to evade the body's defences and preventing the immune system from killing them.

The researchers are now keen to investigate precisely how the genetic variations that they have uncovered affect the activity of Factor H and Factor H-related proteins.

This study involved collaboration between researchers at Imperial College London and clinicians at Imperial College Healthcare NHS Trust, as part of the Academic Health Science Centre (AHSC), a unique kind of partnership between the College and the Trust, formed in October 2007. The AHSC's aim is to improve the quality of life of patients and populations by taking new discoveries and translating them into new therapies as quickly as possible.

Other institutions involved in the study were the Alder Hey Children's Hospital, the Genome Institute of Singapore, and other children's centres in the UK, Holland, Austria and Spain.

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For further information please contact:

Laura Gallagher
Research Media Relations Manager
Imperial College London
email: l.gallagher@imperial.ac.uk
Tel: +44(0)20 7594 8432
Out of hours duty press officer: +44(0)7803 886 248

Notes to editors:

1. "Genome-wide association study identifies variants in the CFH region associated with host susceptibility to meningococcal disease" Nature Genetics, Sunday 8 August 2010

Corresponding authors: Michael Levin, Imperial College London; Sonia Davila, Genome Institute of Singapore and Martin L Hibberd, Genome Institute of Singapore.

2. About the Wellcome Trust

The Wellcome Trust is a global charity dedicated to achieving extraordinary improvements in human and animal health. It supports the brightest minds in biomedical research and the medical humanities. The Trust's breadth of support includes public engagement, education and the application of research to improve health. It is independent of both political and commercial interests.
www.wellcome.ac.uk

3. Meningitis Research Foundation funds research to prevent meningitis and septicaemia, and to improve survival rates and outcomes.

The Foundation promotes education and awareness to reduce death and disability, and gives support to people affected.

MRF is currently funding 26 research projects into the prevention, detection and treatment of meningitis and septicaemia. The Foundation has spent £16 million on research since its inception in 1988.
www.meningitis.org

4. About Imperial College London

Consistently rated amongst the world's best universities, Imperial College London is a science-based institution with a reputation for excellence in teaching and research that attracts 14,000 students and 6,000 staff of the highest international quality. Innovative research at the College explores the interface between science, medicine, engineering and business, delivering practical solutions that improve quality of life and the environment - underpinned by a dynamic enterprise culture.

Since its foundation in 1907, Imperial's contributions to society have included the discovery of penicillin, the developmen t of holography and the foundations of fibre optics. This commitment to the application of research for the benefit of all continues today, with current focuses including interdisciplinary collaborations to improve global health, tackle climate change, develop sustainable sources of energy and address security challenges.

In 2007, Imperial College London and Imperial College Healthcare NHS Trust formed the UK's first Academic Health Science Centre. This unique partnership aims to improve the quality of life of patients and populations by taking new discoveries and translating them into new therapies as quickly as possible.