Environmental and Molecular Drivers of the α-Gal Syndrome

作者：Alejandro Cabezas‐Cruz, Adnan Hodžić, Patricia Román‐Carrasco, Lourdes Mateos‐Hernández, Georg Gerhard Duscher, Deepak K. Sinha, Wolfgang Hemmer, Ines Swoboda, Agustín Estrada‐Peña, José de la Fuente · 发表于：Frontiers in Immunology · 年份：2019 · DOI：10.3389/fimmu.2019.01210 · 被引用次数：133 · 研究领域：Food Allergy and Anaphylaxis Research、Xenotransplantation and immune response、Herpesvirus Infections and Treatments

The α-Gal syndrome (AGS) is a type of allergy characterized by an IgE antibody (Ab) response against the carbohydrate Galα1-3Galβ1-(3)4GlcNAc-R (α-Gal), which is present in glycoproteins from tick saliva and tissues of non-catarrhine mammals. Recurrent tick bites induce high levels of anti-α-Gal IgE Abs that mediate delayed hypersensitivity to consumed red meat products in humans. Initially, it was thought that the origin of tick-derived α-Gal was either residual blood meal mammalian glycoproteins containing α-Gal or tick gut bacteria producing this glycan. However, recently tick galactosyltransferases were shown to be involved in α-Gal synthesis with a role in tick and tick-borne pathogen life cycles. Two mechanisms might explain the production of anti-α-Gal IgE Abs after tick bites. The first mechanism proposes that the α-Gal antigen on tick salivary proteins is presented to antigen-presenting cells and B-lymphocytes in the context of Th2 cell-mediated immunity induced by tick saliva. The second mechanism is based on the possibility that tick salivary prostaglandin E2 triggers Immunoglobulin class switching to anti-α-Gal IgE-producing B cells from preexisting mature B cells clones producing anti-α-Gal IgM and/or IgG. Importantly, blood group antigens influence the capacity of the immune system to produce anti-α-Gal Abs which in turn impacts individual susceptibility to AGS. Individuals with blood group B and reduced levels of anti-α-Gal Abs have lower risk to develop AGS. B...