Interesting papers in PID

Articles review - May

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By Amos Etzioni


Congenital disorders of glycosylation (CGD) are known to cause severe neurodevelopment abnormalities. Up to recently, the only CGD associated with immunodeficiency was LADII (CGD-IIc) which is due to mutation in the gene encoded for the specific transporter of fucose into the Golgi apparatus.

In the May issue of the Journal of Allergy Clinical Immunology, 2 articles appearing back to back described several patients with glycosylation defect leading to a hyper IgE syndrome (HIES)(1,2). Researchers from the NIH and from Freiburg, using whole exome sequencing, found mutations in phosphoglucomutase 3 (PGM3) (an enzyme which catalyzes a key step in the synthesis of n-glycants), in a group of patients with AR-HIES. As opposed to patients with STAT3 or DOCK8 mutations, these patients  suffer from neurocognitive  deficiency associated with severe atopy, immune deficiency and autoimmunity.

Interesting enough, at the same time, another defect in glycosylation associated with immune abnormalities was report (3). Sergio Rosenzweig and his colleagues described in the New Eng J Med 2 patients with mutation in MOGS, the gene encoding for the first enzyme in the processing pathway of n-linked oligosaccharide. The patients had a paradoxical immunologic phenotype. Severe hypogammaglobulinemia, due to a shorten immunoglobulin half time, or the one side. On the other side they showed resistance to viral infection most probably due to impaired viral replication and defective cellular entry by viruses.

        1. Zhang Y, Yu x et al. Autosomal recessive phosphoglucomutase 3 (PGM3) mutations link glycosylation defects with atopy, immune deficiency,               autoimmunity and neurocognitive impairment. J Allergy Clin Immunol 133;1400-9, 2014. 


        2. Sassi A, Lazaroski S et al. hypomorphic homozygous mutations in phosphoglucomutase 3 (PGM3) impair immunity and increase serum IgE levels. J           Allergy Clin Immunol. 133;1410-9, 2014.


        3. Sadat MA, Noir S et al. glycosylation hypogammaglobulinemia and resistance to viral infections. New Eng J Med. 370;1620-5, 2014.