PURPOSE OF REVIEW: The hyper-IgE syndromes have been recognized as a group of primary immunodeficiencies characterized by eczema, recurrent skin and lung infections, and elevated serum IgE. Recently, mutations in phosphoglucomutase 3 (encoding PGM3, which is involved in the protein glycosylation pathway) have been identified in autosomal recessive forms of hyper-IgE syndromes. RECENT FINDINGS: Autosomal recessive, hypomorphic PGM3 mutations cause a multisystem disorder, characterized by both a congenital glycosylation disease and a hyper-IgE syndrome. The reported mutations in PGM3 led to an impaired biosynthesis of UDP-GlcNAc and impaired tri-antennary and tetra-antennary N-glycan structures. Laboratory results in patients showed eosinophilia, a T-cell proliferation defect, and a reversed CD4/CD8 ratio. The impaired glycosylation in PGM3-mutant patients will not only affect proteins involved in the immune system, and thus causes a multisystem phenotype. SUMMARY: The identification of hyper-IgE syndromes-associated mutations in PGM3 provides the basis for future studies on the pathophysiology and the molecular mechanisms of eczema, IgE dysregulation, and increased susceptibility to infections.
PURPOSE OF REVIEW: The hyper-IgE syndromes have been recognized as a group of primary immunodeficiencies characterized by eczema, recurrent skin and lung infections, and elevated serum IgE. Recently, mutations in phosphoglucomutase 3 (encoding PGM3, which is involved in the protein glycosylation pathway) have been identified in autosomal recessive forms of hyper-IgE syndromes. RECENT FINDINGS: Autosomal recessive, hypomorphic PGM3 mutations cause a multisystem disorder, characterized by both a congenital glycosylation disease and a hyper-IgE syndrome. The reported mutations in PGM3 led to an impaired biosynthesis of UDP-GlcNAc and impaired tri-antennary and tetra-antennary N-glycan structures. Laboratory results in patients showed eosinophilia, a T-cell proliferation defect, and a reversed CD4/CD8 ratio. The impaired glycosylation in PGM3-mutant patients will not only affect proteins involved in the immune system, and thus causes a multisystem phenotype. SUMMARY: The identification of hyper-IgE syndromes-associated mutations in PGM3 provides the basis for future studies on the pathophysiology and the molecular mechanisms of eczema, IgE dysregulation, and increased susceptibility to infections.
Authors: M Elkuch; V Greiff; C T Berger; M Bouchenaki; T Daikeler; A Bircher; A A Navarini; I Heijnen; M Recher Journal: Clin Exp Immunol Date: 2017-01-11 Impact factor: 4.330