Serum HER2 levels are increased in cats with mammary carcinomas and predict tissue HER2 status

Background: Alpha-Gal syndrome (AGS) is a tick-borne food allergy caused by IgE antibodies against the glycan galactose-alpha-1,3-galactose (α-Gal) present in glycoproteins and glycolipids from mammalian meat. To advance in the diagnosis and treatment of AGS, further research is needed to unravel the molecular and immune mechanisms underlying this syndrome. The objective of this study is the characterization of tick salivary components and proteins with and without α-Gal modifications involved in modulating human immune response against this carbohydrate. Methods: Protein and α-Gal content were determined in tick saliva components, and proteins were identified by proteomics analysis of tick saliva fractions. Pathophysiological changes were recorded in the zebrafish (Danio rerio) model after exposure to distinct Ixodes ricinus tick salivary components. Serum samples were collected from zebrafish at day 8 of exposure to determine anti-α-Gal, anti-glycan, and anti-tick saliva protein IgM antibody titers by enzyme-linked immunosorbent assay (ELISA). Results: Zebrafish treated with tick saliva and saliva protein fractions combined with non-protein fractions demonstrated significantly higher incidence of hemorrhagic type allergic reactions, abnormal behavioral patterns, or mortality when compared to the phosphate-buffered saline (PBS)-treated control group. The main tick salivary proteins identified in these fractions with possible functional implication in AGS were the secreted protein B7P208-salivary antigen p23 and metalloproteases. Anti-α-Gal and anti-tick salivary gland IgM antibody titers were significantly higher in distinct saliva protein fractions and deglycosylated saliva group when compared with PBS-treated controls. Anti-glycan antibodies showed group-related profiles. Conclusions: Results support the hypothesis that tick salivary biomolecules with and without α-Gal modifications are involved in modulating immune response against this carbohydrate. Graphical

In the last two years, the coronavirus disease 19 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been a scientific and social challenge worldwide. Vaccines have been the most effective intervention for reducing virus transmission and disease severity. However, genetic virus variants are still circulating among vaccinated individuals with different disease symptomatology. Understanding the protective- or disease-associated mechanisms in vaccinated individuals is relevant to advances in vaccine development and implementation. To address this objective, serum-protein profiles were characterized by quantitative proteomics and data-analysis algorithms in four cohorts of uninfected and SARS-CoV-2-infected vaccinated individuals with asymptomatic, non-severe, and severe disease symptomatology. The results show that immunoglobulins were the most overrepresented proteins in infected cohorts when compared to PCR-negative individuals. The immunoglobulin profile varied between different infected cohorts and correlated with protective- or disease-associated capacity. Overrepresented immunoglobulins in PCR-positive individuals correlated with protective response against SARS-CoV-2, other viruses, and thrombosis in asymptomatic cases. In non-severe cases, correlates of protection against SARS-CoV-2 and HBV together with risk of myasthenia gravis and allergy and autoantibodies were observed. Patients with severe symptoms presented risk for allergy, chronic idiopathic thrombocytopenic purpura, and autoantibodies. The analysis of underrepresented immunoglobulins in PCR-positive compared to PCR-negative individuals identified vaccine-induced protective epitopes in various coronavirus proteins, including the spike receptor-binding domain RBD. Non-immunoglobulin proteins were associated with COVID-19 symptoms and biological processes. These results evidence host-associated differences in response to vaccination and the possibility of improving vaccine efficacy against SARS-CoV-2.

The alpha‐Gal syndrome (AGS) is an underdiagnosed tick‐borne allergy characterized by both immediate and delayed IgE‐mediated anaphylactic reactions to the galactose‐alpha‐1,3‐galactose (alpha‐Gal) epitope. Common manifestations include gastrointestinal, cutaneous, and respiratory symptoms appearing 2–6 h after the consumption of mammalian meat or derived products. Zebrafish ( Danio rerio ) are emerging as essential animal models in biomedical studies, due to their anatomical, genetic, and physiological similarities to humans, with significant applications in toxicology, behavioral research, oncology, and inflammation studies. The mechanisms associated with AGS are sustained by studies in the humanized α1,3GalT‐KO C57BL/6 mouse ( Mus musculus ) and zebrafish animal models for the production of anti‐alpha‐Gal antibodies in response to tick saliva, the development of allergic reactions in animals sensitized with tick protein extracts following mammalian meat consumption, and the identification of immune mechanisms. The immune mechanisms characterized in both models are associated with a skewed type 2 immune response, triggering Toll‐Like receptor (TLR) signaling pathways, IL‐4 production, and humoral activity. These results support the use of both models rather than a single one for a more comprehensive characterization of AGS‐associated immune mechanisms. In this study, we focused on the use of zebrafish as a model for biomedicine research in immunity, infectious, and allergic diseases, with a particular emphasis on the AGS and the identification of candidate therapeutic interventions. Based on insights from multiple studies, we concluded that zebrafish is a suitable model for studying the AGS, considering the addressed limitations and in combination with the α1,3GalT‐KO mouse model.