Causes of immunodeficiency in children

Scientists identify cause of congenital immunodeficiency

08/18/2014

European scientists have managed to identify the genetic cause of congenital immunodeficiency in children. The condition may be treatable with a known biotech drug.

Genetic cause of immunodeficiency
Scientists in Europe have managed to identify the genetic cause of congenital immunodeficiency in children. At first, doctors and scientists were from Haunerschen Children's Hospital in Munich, the Research Center for Molecular Medicine in Vienna (CeMM) and the Vienna University Children's Hospital as well as from other research centers in Europe came to the conclusion that the cause of the immunodeficiency SCN occurring in children (Severe Congenital Neutropenia ) is apparently a defect in the gene JAGN1. The researchers reported in the journal „Nature Genetics“ about their results.

Congenital disorders caused by mutations
The scientists had found this mutation in 14 children with such disorders. In SCN, sufferers may experience symptoms such as premature tooth loss, gingivitis, frequent bacterial infections, fever, mouth ulcers, diarrhea, sore throat or chills. Also, an increased risk of acute myeloid leukemia and bone marrow diseases is associated with it. Kaan Boztug from the Vienna CeMM explained according to a message from the news agency APA: „The discovery of JAGN1 deficiency is an example of how innate immunity disorders can be caused by mutations in genes that were previously unknown to play a role in the immune system.“

Primarily due to serious deficiency of certain immune cells
Boztug is the first author of one of the two studies and discoverer of the first patients with mutations in the JAGN1 gene. Together with the Munich scientist Christoph Klein, he was able to discover affected families and identify the genetic defect. According to these findings, the severe congenital immunodeficiency SCN, which is primarily based on a serious deficiency of certain immune cells, the so-called neutrophilic granulocytes, is due to a defect in the development of neutrophilic granulocytes by the JAGN1 defect.

Researchers tested possible drugs for the treatment
As a result, Gerald Wirnsberger at the Institute of Molecular Biotechnology of the Austrian Academy of Sciences bred mice with this genetic defect and the same immunodeficiency as in humans. It has been found that the JAGN1 defect in the neutrophil granulocytes deficient in actively tracking pathogens such as bacteria or fungi. In addition, they also less toxic to the bacteria or fungi or pour less of it to kill them. The researchers finally tested - also on mice - for the treatment of possible drugs. They used the biotech blood growth factors G-CSF and GM-CSF, which have been known for years, to promote the formation of granulocytes. These drugs are mainly used to support the treatment of cancer patients to treat treatment-related immunodeficiency.

Medicinal products may affect patients with genetic defects
Interestingly, in the mice with the JAGN1 defect, only GM-CSF (granulocyte macrophage colony stimulating factor) was effective. „Treatment with GM-CSF protected mice with the mutation from accelerated weight loss and faster death following an artificial infection with Candida albicans“, so the scientists. The yeast Candida albicans is, among other things, the main pathogen for a vaginal yeast infection. In the laboratory, GM-CSF also corrected the lack of white cell defense against the fungi in human bone marrow cells. For patients with a JAGN1 gene defect, this means that GM-CSF could also work for them. It is now being investigated in clinical studies to see if this is really the case. (Ad)