Researchers Identify New Molecular Mechanism Related to Severe Anaphylaxis; Mutation in KARS Gene Linked to Life-Threatening Reaction to Paper Wasp Venom

Anaphylaxis is a systemic allergic reaction that can affect the skin, the gastrointestinal tract, the respiratory system, and the cardiovascular system. The most severe form of anaphylaxis is anaphylactic shock, which features hypotension and can cause death. This reaction can have several causes, such as allergic reactions to food, medicines, or insect venom. The molecular mechanisms that cause the severity of these kinds of reactions is still unknown. In a study led by researchers at the University of Barcelona (UB) and IDIBAPS (August Pi i Sunyer Biomedical Research Institute), researchers analyzed the mutation of a gene detected in a patient who suffered from recurrent anaphylactic shocks caused by the allergy to paper wasp venom (Polistes dominula). The results, published online on December 29, 2020 in the Journal of Allergy and Clinical Immunology, revealed a new molecular mechanism that can control the degree of severity in an anaphylactic reaction (see image below). The study was led by UB and IDIBAPS researchers Margarita Martín, PhD, and Rosa Muñoz-Cano, MD, PhD. Both are members of the Asthma, Allergic and Adverse Reactions Network (ARADyAL) of the Carlos III Institute. The article is titled “Mutation in KARS: A Novel Mechanism for Severe Anaphylaxis.” Researchers carried out the biochemical, functional, and structural characterization of mutations in the KARS gene (which codes for lysyl-tRNA synthetase, LysRS), detected in the patient. “The study combines clinical data from the patient with severe anaphylaxis and carrier of a mutation in the KARS gen, with biochemical, functional, and structural data that show an anomalous function of the LysRS protein, coded by this gene,” notes Dr. Martín.
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