Intrinsic risk factors for alpha-gal syndrome in a case-control study, 2019 to 2020.

BACKGROUND: Alpha-gal syndrome (AGS) is an allergy to galactose-α-1,3-galactose (alpha-gal), a carbohydrate found in most mammals. Evidence indicates that AGS develops after a tick bite, and in the United States, AGS is most associated with bites from Amblyomma americanum (lone star tick); however, not all persons bitten by ticks develop clinical AGS. OBJECTIVE: To investigate intrinsic risk factors associated with the development of AGS. METHODS: We performed a case-control study among adults presenting for diagnosis or management of AGS at an allergy clinic in North Carolina during 2019 to 2020 and compared them with controls enrolled from 2 nearby internal medicine clinics. A questionnaire gathered epidemiologic and tick exposure data, and blood was obtained for alpha-gal-specific IgE and other testing. RESULTS: The 82 enrolled case patients and 191 controls did not differ significantly by age or sex. Case patients were more likely than controls to have A or O blood types (non B-antigen), have experienced childhood allergies, and have a family history of AGS and other food allergies. Case patients were also more likely to report experiencing long healing times for insect bites or stings and a family history of allergy to stinging or biting insects. CONCLUSION: This study suggested that intrinsic factors contribute to risk of developing AGS. Some traits are genetic, but common behaviors among households and family units likely also contribute. Identification of these risk factors can inform personal risk, aid health care providers in understanding susceptible populations, and contribute to ongoing understanding of AGS epidemiology.

Association between lone star tick bites and increased alpha-gal sensitization: evidence from a prospective cohort of outdoor workers.

BACKGROUND: Alpha-gal is an oligosaccharide implicated in delayed anaphylaxis following red meat consumption. Exposure to tick bites has been correlated with development of an allergic response to alpha-gal. However, evidence prospectively linking exposure to a single tick species and an immune response to alpha-gal is lacking. METHODS: We used serum samples from a prior study cohort of outdoor workers in North Carolina, USA, with high exposure to the lone star tick, Amblyomma americanum, to prospectively evaluate the relationship between tick bites and anti-alpha-gal IgE antibodies. RESULTS: Individuals who reported exposure to one or more tick bites were significantly more likely to have a positive change in anti-alpha-gal IgE compared to individuals with no reported tick bites. This relationship was not dependent on time. A trend toward increasing number of tick bites and increased anti-alpha-gal IgE levels was observed but not statistically significant. CONCLUSION: To our knowledge, this is the first study to prospectively link documented exposure to A. americanum bites and increased sensitization to alpha-gal in a cohort of outdoor workers. Our results support the role of A. americanum as likely agents for eliciting an allergic response to red meat, and highlight the importance of preventing tick bites.

A chemical conjugate of the tick P0 peptide is efficacious against Amblyomma mixtum.

After Rhipicephalus microplus, the most important tick species affecting livestock industry in Cuba belong to the Amblyomma genus. There are few reports of effective vaccine antigens for these species. Recently, vaccination and challenge trials using a peptide from the P0 acidic ribosomal protein of R. microplus ticks (pP0) as antigen have shown an efficacy around 90% against tick species from the Rhipicephalus genus. Given the high degree of sequence conservation among tick species, pP0 could be an antigen of versatile use in anti-tick vaccine formulations. In this paper, seven rabbits were immunized with a chemical conjugate of pP0 to keyhole limpet haemocyanin. Rabbits were challenged with an average of 1,900 Amblyomma mixtum larvae from a Cuban tick strain. The average number of recovered fed larvae and the viability of larvae in the moulting process were significantly lower in vaccinated animals compared with the control group. The overall vaccine efficacy of the P0 peptide antigen is 54% according to the calculated parameters.

Amblyomma sculptum Salivary Protease Inhibitors as Potential Anti-Tick Vaccines.

Amblyomma sculptum is the main tick associated with human bites in Brazil and the main vector of Rickettsia rickettsii, the causative agent of the most severe form of Brazilian spotted fever. Molecules produced in the salivary glands are directly related to feeding success and vector competence. In the present study, we identified sequences of A. sculptum salivary proteins that may be involved in hematophagy and selected three proteins that underwent functional characterization and evaluation as vaccine antigens. Among the three proteins selected, one contained a Kunitz_bovine pancreatic trypsin inhibitor domain (named AsKunitz) and the other two belonged to the 8.9 kDa and basic tail families of tick salivary proteins (named As8.9kDa and AsBasicTail). Expression of the messenger RNA (mRNA) encoding all three proteins was detected in the larvae, nymphs, and females at basal levels in unfed ticks and the expression levels increased after the start of feeding. Recombinant proteins rAs8.9kDa and rAsBasicTail inhibited the enzymatic activity of factor Xa, thrombin, and trypsin, whereas rAsKunitz inhibited only thrombin activity. All three recombinant proteins inhibited the hemolysis of both the classical and alternative pathways; this is the first description of tick members of the Kunitz and 8.9kDa families being inhibitors of the classical complement pathway. Mice immunization with recombinant proteins caused efficacies against A. sculptum females from 59.4% with rAsBasicTail immunization to more than 85% by immunization with rAsKunitz and rAs8.9kDa. The mortality of nymphs fed on immunized mice reached 70-100%. Therefore, all three proteins are potential antigens with the possibility of becoming a new tool in the control of A. sculptum.