The alpha-Gal syndrome: new insights into the tick-host conflict and cooperation

Abstract

This primer focuses on a recently diagnosed tick-borne allergic disease known as the alpha-Gal syndrome (AGS). Tick bites induce in humans high levels of IgE antibodies against the carbohydrate Galα1-3Galβ1-(3)4GlcNAc-R (α-Gal) present on tick salivary glycoproteins and tissues of non-catarrhine mammals, leading to the AGS in some individuals. This immune response evolved as a conflict and cooperation between ticks and human hosts including their gut microbiota. The conflict is characterized by the AGS that mediate delayed anaphylaxis to red meat consumption and certain drugs such as cetuximab, and immediate anaphylaxis to tick bites. The cooperation is supported by the capacity of anti-α-Gal IgM and IgG antibody response to protect against pathogens with α-Gal on their surface. Despite the growing diagnosis of AGS in all world continents, many questions remain to be elucidated on the tick proteins and immune mechanisms triggering this syndrome, and the protective response against pathogen infection elicited by anti-α-Gal antibodies. The answer to these questions will provide information for the evaluation of risks, diagnosis and prevention of the AGS, and the possibility of using the carbohydrate α-Gal to develop vaccines for the control of major infectious diseases. Electronic supplementary material The online version of this article (10.1186/s13071-019-3413-z) contains supplementary material, which is available to authorized users.

Allergic Reactions and Immunity in Response to Tick Salivary Biogenic Substances and Red Meat Consumption in the Zebrafish Model

“…Humans evolved with the inactivation of the α1,3-GalT gene, which resulted in the recognition of the carbohydrate α-Gal as a non-self-antigen, thus inducing the production of high antibody titers against this molecule (Galili, 2018). This evolutionary trait benefits humans by providing immunity to pathogens containing α-Gal in the surface while increasing the risks of developing the AGS triggered by the IgE antibody response against α-Gal present in glycoproteins and glycolipids from tick saliva and tissues of non-catarrhine mammals (Commins et al, 2009;Van Nunen et al, 2009;Platts-Mills et al, 2015;Steinke et al, 2015;Galili, 2018;Cabezas-Cruz et al, 2019;de la Fuente et al, 2019;Hilger et al, 2019;Román-Carrasco et al, 2019;Park et al, 2020). The AGS is characterized by delayed anaphylaxis to red meat consumption and immediate anaphylaxis to tick bites, xenotransplantation, and certain drugs such as cetuximab (Mateos-Hernández et al, 2017;Hilger et al, 2019).…”

“…The AGS is characterized by delayed anaphylaxis to red meat consumption and immediate anaphylaxis to tick bites, xenotransplantation, and certain drugs such as cetuximab (Mateos-Hernández et al, 2017;Hilger et al, 2019). Despite recent advances in the study of the AGS (Commins et al, 2009;Van Nunen et al, 2009;Platts-Mills et al, 2015;Steinke et al, 2015;Mateos-Hernández et al, 2017;Galili, 2018;Cabezas-Cruz et al, 2019;de la Fuente et al, 2019;Hilger et al, 2019), the immune-mediated mechanisms induced by tick bites and leading to the AGS have been only partially characterized in α1,3-GalT-KO mice (Araujo et al, 2016;Chandrasekhar et al, 2019). The development of new animal models for tick-borne allergies such as the AGS would contribute to these studies.…”

“…Additionally, tick bites can induce in humans high levels of immunoglobulin E (IgE) antibodies against the carbohydrate Galα1-3Galβ1-(3)4GlcNAc-R (α-Gal) present in glycoproteins and glycolipids from tick saliva that mediate delayed anaphylaxis to red meat consumption, and immediate anaphylaxis to tick bites, xenotransplantation, and certain drugs such as cetuximab (Mateos-Hernández et al, 2017;Hilger et al, 2019). These anaphylactic reactions are known as the alpha-Gal syndrome (AGS) or red meat allergy and are now the focus of recent investigations (Commins et al, 2009;Van Nunen et al, 2009;Platts-Mills et al, 2015;Steinke et al, 2015;Galili, 2018;Cabezas-Cruz et al, 2019;de la Fuente et al, 2019;Hilger et al, 2019).…”

Emerging tick-borne pathogens of public health importance: a mini-review

“…This allergic reaction is attributed to the bite of certain tick species and is considered to be an emerging condition around the world [122,123]. Several hundred to several thousand cases have been documented in North America, Europe, Australia and Japan; single cases have been reported from South America and Africa [124]. Some of the typical symptoms associated with the alpha-gal syndrome include urticarial or anaphylactic reactions that are generally manifested a few hours after eating red meat, including pork, lamb, beef, or kangaroo.…”

Infection with Toxocara canis Inhibits the Production of IgE Antibodies to α-Gal in Humans: Towards a Conceptual Framework of the Hygiene Hypothesis?

“…However, hyperproduction of specific IgE Abs to α-Gal triggered by bites of ixodid ticks (Acari: Ixodidae) may lead to a delayed and potentially fatal anaphylactic reaction to mammalian meats (e.g., beef, pork, lamb) and other α-Gal-containing products [12,13]. This recently recognized type of food allergy, also known as α-Gal syndrome (AGS) or red meat allergy, seems to be an emerging global problem with an increasing prevalence reported in all continents [14,15]. In general, affected patients suffer from urticaria, angioedema, abdominal pain, and anaphylaxis that usually occur 3-6 h following the consumption of mammalian food products [12].…”