From the moment we are born, we all come into continuous contact with microbes that can cause disease. To deal with them, we have a highly effective immune system that allows our bodies to identify and eliminate agents that cause infections. Part of this mechanism is innate (already present at the time of birth) and the remaining part improves as we come into contact with new pathogens.
From birth, the immune system reacts to infection with an inflammatory response that cause fever, pain, and an increased number of white blood cells in the blood, together with dilation of the blood vessels in the affected area. This reaction serves to isolate and destroy the pathogen and is a warning that something is wrong.
An international study, which involved the participation of Hospital Germans Trias (pediatrics and immunology), Hospital Clínic (immunology) and Hospital Sant Joan de Déu (pediatrics) in Barcelona and Hospital Dr. Negrín in Las Palmas de Gran Canaria, has identified a strange disease in which the innate immune system works in an irregular fashion. The study describes 9 cases of children severely infected by common bacteria, specifically pneumococci and staphylococci, who do not react to the infection with an inflammatory response; that is, they have no fever and there is no detected increase in the number of white blood cells in the blood. By the time they see a doctor, the infection is widespread. In fact, 3 of the children, aged between 1 and 11 months, died.
The most curious aspect is that the affected children were able to see off other infections and responded to vaccines and antibiotics. This means that their immune system was able to detect other microbes and stimulate the production of antibodies.
A genetic analysis of the children finally revealed a deficiency in a gene, known as myD88, which is essential for correctly identifying the presence of an infection caused by pathogens and responding to it.
In order to make sure that this was the true cause of the disease, the researchers used genetically modified animals with this gene altered.
Unlike the affected children, the animals were susceptible to a large number of pathogens, not just pneumococci and staphylococci. This suggests that the human immune system has alternative mechanisms to compensate for the MyD88 deficiency. Another suspicion of the study's authors is that the affected children will improve with age. New research is needed to confirm these hypotheses.
The 6 surviving patients are now aged between 3 and 16 years. They are being treated with antibiotics effective against pneumococcus and staphylococcus infections and lead a normal life.
The study was coordinated by researchers from the Necker hospital in Paris (attached to the INSERM) and, as well as the 4 Spanish centres, the study included participation by centres from the US, Thailand, Turkey, Portugal, France, UK, Hungary, Israel and Canada. Three of the children were diagnosed at Hospital Germans Trias, 2 at Hospital Sant Joan de Déu, 2 in Portugal, 1 in France, and 1 in Turkey. The study will be published in the online edition of the journal Science on 1 August.
For further information:
Hospital Germans Trias
Jordi Morató
jmorato.germanstrias@gencat.cat
Tel. 93 497 89 94 – 695 56 09 80
www.gencat.cat/ics/germanstrias
Hospital Clínic
Marc de Semir
mdesemir@clinic.ub.es
Tel. 93 227 57 00
www.hospitalclinic.org
Hospital Sant Joan de Déu
Albert Moltó
amolto@hsjdbcn.org
Tel. 93 253 21 50
www.hsjdbcn.org
Article reference
Horst von Bernuth, Capucine Picard, Zhongbo Jin, Rungnapa Pankla, Hui Xiao, Cheng-Lung Ku, MayaChrabieh, Imen Ben Mustapha, Pegah Ghandil, Yildiz Camcioglu, Júlia Vasconcelos, Nicolas Sirvent, Margarida Guedes, Artur Bonito Vitor, María José Herrero-Mata, Juan Ignacio Aróstegui, Carlos Rodrigo, Laia Alsina, Estibaliz Ruiz-Ortiz, Manel Juan, Claudia Fortuny, Jordi Yagüe, Jordi Antón, Mariona Pascal, Huey-Hsuan Chang, Lucille Janniere, Yoann Rose, Ben-ZionGarty, Helen Chapel, Andrew Issekutz, László Maródi, CarlosRodriguez-Gallego, Jacques Banchereau, LaurentAbel, Xiaoxia Li, Damien Chaussabel, AnnePuel, Jean-Laurent Casanova. Pyogenic Bacterial Infections in Humans with MyD88 Deficiency. Science Ago 1 [epub ahead of print]
Journal
Science