Genome analyses help diagnose immune deficiency disorders

Children who experience recurrent invasive pneumococcal infections exhibit mutations in genes that encode two molecules important for the immune system’s response to infection. 

Loss of function of these genes, called IRAK4 and MyD88, interrupts a critical pathway for sensing pathogens and producing an inflammatory response. 

This leads to susceptibility to certain types of bacteria that commonly cause infections such as pneumonia, skin infections and septicemia. 

By conducting a genome-wide analysis of patients exhibiting IRAK4 and MyD88 deficiencies, published in Nature Immunology¹, researchers developed a robust approach for assessing the competency of the innate immune system — that part of our immunity that we are born with and which forms our first line of defense against pathogens.

The researchers exposed blood samples from IRAK4- and MyD88-deficient patients to purified agonists that target specific immune receptors and to whole killed bacteria. They then assessed how gene expressions reacted to the foreign elements and how this affected the immune response. 

They found that an immune response failed to launch in the case of purified agonists. On the other hand, the response to whole bacteria was selectively affected. This suggests the existence of alternative pathways that can maintain resistance to some pathogens.

The approach used here can also be useful to detect defects in immunity as the result of aging or for predicting responses to vaccines. 

“The incidence of immune deficiencies in the Middle East is quite high,” says Damien Chaussabel, one of the investigators in the study and the incoming head of the Department of Systems Biology at Sidra Medical and Research Center in Qatar. As a result, the approach used in this study will be quite relevant to the problems that Sidra will be tackling, he adds.

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