An Action Medical Research project is seeking to improve protection against serious childhood infections.
MBL binds and kills N. meningitidis. Red arrows show the sites where MBL binds to the bacterium
Humans have two main forms of defence against infection. The first you are born with and is called the innate immune system. The second is known as the acquired immune system as it develops after birth and provides a ‘memory’ of all infections that we get throughout life.
The acquired immune system takes time to develop but is working well by the time children start school. It is because this acquired immune system takes time to develop that babies and young children get many more infections than older children and adults. Babies and children rely heavily on the innate immune system for their defence against infection.
In these early years of life, a protein called mannose-binding lectin (MBL) is particularly important for attacking the viruses, bacteria and fungi that can cause infections. This protein recognises sugars on the surface of these infectious organisms and binds to them.
In the picture MBL can be seen attached to the surface of the major bacterium that causes meningitis (N. meningitidis). Once bound it can kill the organism and then help clear it away so that it can no longer cause harm.
It is now 15 years since Professor Mac Turner discovered at Great Ormond Street Hospital (GOSH) that some people have low levels of MBL in their blood. In fact this deficiency of MBL is quite common, with about a third of the population affected. Subsequent work, both at GOSH (some of it funded by Action Medical Research) and other centres, has shown that low levels of MBL puts children at greater risk of getting infection.
Most of the time these infections are what we would consider minor, such as coughs and colds. It does however go a long way to explain why some children seem to always get coughs and colds while others get through childhood with very few infections.
A child with Meningococcal Septicaemia. Note the characteristic rash on the legs
As the levels of MBL are genetically determined it means that children within a single family can have different levels of MBL and therefore different frequencies of infection. For example, if a mother has low levels and the father has normal levels then only some of their children will have low MBL levels.
While most infections in children with low MBL levels are minor, there are a few infections that are more serious. These are the ones that cause meningitis (infection of the surface of the brain) and septicaemia (severe infection of the blood). These are uncommon. However, when they occur they are serious and can cause death.
Advances in Intensive Care and earlier recognition of symptoms by parents and doctors have improved outcomes for children. But serious infections are still responsible for many admissions to Intensive Care Units and many of the deaths.
… in a study of nearly 200 children admitted to Intensive Care, nearly all the children with septicaemia had low levels of MBL …
With the help of Action Medical Research, researchers at GOSH have been able to investigate how MBL helps protect children from these infections. What they have been able to show is that MBL seems to be particularly important in preventing children from getting septicaemia. Indeed, in a study of nearly 200 children admitted to Intensive Care, nearly all the children with septicaemia had low levels of MBL. Children who had normal levels of MBL were very unlikely to get septicaemia.
Exactly why MBL is so important in protecting against this type of infection is as yet unclear. However the team at GOSH, led by Professor Nigel Klein, has been able to show that MBL influences the way the body responds to the micro-organism when it first causes an infection. As such there is a real possibility that in the near future MBL could be used as a treatment for these serious infections.
Action Medical Research played a crucial role in supporting the initial research that led to the discovery that MBL was very important in protection against childhood infections. £107,000 funding of this additional research over the last three years has now laid the foundation for introducing a novel therapy for critically ill children.
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Action Medical Research
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Action Medical Research is one of the country’s leading medical research charities. For over fifty years we have been funding pioneering research into a wide range of illnesses and conditions. Find out more about us at www.action.org.uk
This article was printed from http://www.action.org.uk/touching_lives/2004/03/childhood_infections/
It first appeared in our Touching Lives magazine in March 2004.
