Neurobiology and Insect Physiology Research (68)Insect Resistance and Genetics (60)Insect and Pesticide Research (46)Vector-borne infectious diseases (35)Insect and Arachnid Ecology and Behavior (33)
α-Gal syndrome (AGS), a tick bite-associated allergy to mammalian meat, affects an estimated 450,000 Americans, with the highest prevalence concentrated in the US South and Southeast. The lone star tick (), ubiquitous across the region, transmits AGS sensitization, making reexposure nearly inevitable for outdoor workers and residents. Current management relies on dietary avoidance of mammalian products of an indeterminant length, a recommendation that is neither practical in a region where mammalian meat is central to cuisine and culture nor evidence based regarding duration or necessity. In the absence of treatment options, patients are turning to alternative interventions such as acupuncture protocols that lack validation from controlled trials. Meanwhile, oral immunotherapy has demonstrated safety and efficacy for other immunoglobulin E-mediated food allergies, and individual case reports suggest desensitization may be feasible for AGS syndrome. The US South, with its high disease burden, clinical expertise, and patient populations, is uniquely positioned to lead the rigorous phase 1 and phase 2 trials needed to develop evidence-based treatment alternatives. Without such research, patients have only dietary restriction as an evidence-based option and may seek purported treatments that lack rigorous validation.
Sempa J, Brenes P, Tegeler A, Looper J, Chao M, et al.
Nutrients •
: Alpha-gal syndrome (AGS) is a tick-borne allergic condition increasingly prevalent in the Southern, Eastern and Mid-western regions of the United States. This study aims to assess the awareness and understanding of AGS among Kansas residents, focusing on its symptoms, impact, and available management resources. : Two anonymous, self-reported surveys were administered using Qualtrics software [Qualtrics XM, Provo, UT, USA], one targeting Kansas Extension professionals and the other directed at Kansas community residents. Participants from both groups demonstrated general awareness of AGS, with 82 respondents self-identifying as having the condition. Beyond the dietary restrictions associated with the condition, individuals with AGS also faced a range of social, financial and health-related challenges. The study revealed critical gaps in healthcare preparedness and support infrastructure for managing AGS in rural Kansas communities. : While awareness of AGS is increasing in Kansas, individuals affected by this condition continue to encounter significant challenges. These are not limited to personal and emotional hardships but also include systemic challenges in healthcare and community support. Study findings highlight a critical gap between growing awareness and implementation of effective action.
Maldonado-Ruiz LP, Reif KE, Ghosh A, Foré S, Johnson RL, et al.
Scientific reports •
Tick bites, associated with the secretion of tick saliva containing the xenoglycan galactose-alpha-1, 3-galactose (alpha-gal or aGal), are recognized as the causal factors of alpha-Gal syndrome (AGS; or red meat allergy) in humans. AGS occurs after the increased production of IgE antibodies against aGal, which is found in most mammalian cells, except for the Old World monkey and humans. The aGal sensitization event has been linked to an initial tick bite, followed by consumption of red meat containing the aGal glycan, which triggers the onset of the allergic response resulting in urticaria, anaphylaxis, or even death. In North America, the lone star tick, Amblyomma americanum, has been identified as the main culprit for AGS. However, only a subset of the human population exposed to lone star tick bites develops AGS. This suggests the presence of unidentified variables associated with the sensitization event. To evaluate the quantitative variations of the aGal in ticks, we evaluated the differences in aGal levels in different strains of A. americanum ticks partially fed on different blood sources using an artificial feeding system and animal hosts. We found significantly higher aGal levels in the female ticks fed on human blood than those fed on the blood of other mammals with large variations among different tick populations and individuals. We propose that host-specific genetic components in the A. americanum ticks are involved in the production of high aGal epitope in the tick saliva, which provides a part of the explanation for the variables associated with the AGS sensitization event of the tick bite.
Maldonado-Ruiz LP, Boorgula GD, Kim D, Fleming SD, Park Y
Frontiers in immunology •
Recent studies have provided strong evidence indicating that lone star tick bites are a cause of AGS (alpha-gal syndrome, also known as red meat allergy RMA) in humans. AGS is characterized by an increase in IgE antibody production against galactose-alpha-1,3-galactose (aGal), which is a common glycan found in mammalian tissue, except in Old World monkeys and humans. The main causative factor of AGS, the lone star tick (), is broadly distributed throughout the east and midwest of the United States and is a vector of a wide range of human and animal pathogens. Our earlier glycomics study of the salivary glands of partially fed male and female ticks revealed relatively high levels of aGal epitopes. In this study, we found that partially fed males of on bovine blood, which engage in multiple intrastadial feedings, carry a large amount of aGal in the salivary glands. In our current work, we aimed to test whether ticks mediate the transmission of the aGal sensitizer acquired from nonhuman blood to humans in the intrastadial host switch (referred to as the "transmission" hypothesis). To test this hypothesis, we used an alpha-galactosyltransferase knockout mutant mouse (aGT-KO) model system infested with ticks that were unfed or partially fed on bovine blood. Based on the levels of total IgE and specific IgG and IgE antibodies against aGal after tick feedings, aGT-KO mice significantly responded to tick feeding and injection of aGal (Galα1-3Galβ1-4GlcNAc) conjugated to human serum albumin or mouse serum albumin (aGal-HSA or aGal-MSA) by increasing total IgE and aGal-specific IgE levels compared to those in C57BL/6 control mice. All of the treatments of aGT-KO mice involving the feeding of partially fed and unfed ticks functioned as sensitizers that increased the levels of specific IgE against aGal, with large individual variations. The data in this study do not support the "transmission" component of AGS, although they confirmed that aGT-KO mice can be used as a model for RMA studies.
Olajiga OM, Maldonado-Ruiz LP, Fatehi S, Cardenas JC, Gonzalez MU, et al.
Frontiers in immunology •
Dengue virus (DENV) transmitted by the mosquitoes is the etiological agent of dengue fever, one of the fastest-growing reemerging mosquito-borne diseases on the planet with a 30-fold surge in the last five decades. Interestingly, many arthropod-borne pathogens, including DENV type 2, have been reported to contain an immunogenic glycan galactose-alpha1,3-galactose (alpha-Gal or aGal). The aGal molecule is a common oligosaccharide found in many microorganisms and in most mammals, except for humans and the Old-World primates. The loss of aGal in humans is considered to be an evolutionary innovation for enabling the production of specific antibodies against aGal that could be presented on the glycan of pathogens. The objective of this study was to evaluate different anti-aGal antibodies (IgM, IgG, IgG1, and IgG2) in people exposed to DENV. We observed a significant difference in anti-aGal IgG and IgG1 levels among dengue severity classifications. Furthermore, a significant positive correlation was observed between the anti-aGal IgG and the number of days with dengue symptoms in patients. Additionally, both anti-aGal IgM and IgG levels differ between the two geographical locations of patients. While the anti-aGal IgM and IgG2 levels were not significantly different according to the dengue severity levels, age was negatively correlated with anti-aGal IgM and positively correlated with anti-aGal IgG2. Significant involvement of aGal antibodies in Dengue infection processes is suggested based on the results. Our results open the need for further studies on the exact roles and the mechanisms of the aGal antibodies in Dengue infection.