Bethesda - Normally, deficiency in immunoglobulins leads to an increased susceptibility to infections. Not so with two children with rare genetic immunodeficiency. Both are largely spared childhood viral infections, which US researchers in the New England Journal of Medicine (2014; doi: 10.1056 / NEJMoa1302846) attribute to rare genetic defect.
Most children fall ill several times in the first few years of life annually from respiratory diseases, some also from otitis media. The pathogens are usually viruses. The eleven-year-old boy and his six-year-old sister, introduced by Sergio Rosenzweig from the Undiagnosed Diseases Program at the National Institute of Allergy and Infectious Diseases in Bethesda and colleagues, have so far been largely spared viral infections.
However, both had serious bacterial infections gone through. The boy had pneumococcal pneumonia and osteomyelitis caused by St. aureus at young age. His sister had had purulent otitis media and urinary tract infection. There was an explanation for the bacterial infections. The children suffered from lack of antibodies (hypogammaglobulinemia), which protect them from pathogens.
was all the more astonishing the resistance to viral infections, which the researchers therefore investigated. Finally, they were able to determine the cause of defect in the MOGS gene. It codes for the enzyme mannosyl-oligosaccharide glucosidase (MOGS), which provides proteins with sugar residues inside the cell. The disease belongs to the "congenital disorders of glycosylation type IIb" or CDG-IIb.
One consequence of the defective glycosylation was unstable immunoglobulins. Their short half-life was responsible for the hypogammaglobulinemia and probably also for the reduced protection against bacterial pathogens. The authors also attribute the improved protection against certain virus infections to the defective glycosylation.
Some viruses, including the influenza virus but also HIV, have shell with glycoproteins that they obtain during replication. If this does not succeed, for example because the MOGS gene is defective, less resistant viruses are formed, which Rosenzweig can also show in cell cultures.
Other viruses do not depend on glycosylation or they have no envelope at all. These include the adenovirus, the poliovirus and the vaccinia virus. These three viruses showed normal replication in the laboratory tests, and Rosenzweig assumes that the children are susceptible to infections with these viruses.
Substances that inhibit glycosylation could, according to Rosenzweig, be used for treatment of viral diseases are possible. In fact, such agents are already in development. The MOGS inhibitors include, for example, castanospermine, natural substance on the Australian chestnut Castanospermum australe, the effectiveness of which is being tested against herpes simplex infections by Fermentek from Israel.
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