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Loxoscelism: from basic research to the proposal of new therapies

Grant number: 15/17494-1
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): October 01, 2015
Effective date (End): November 30, 2018
Field of knowledge:Biological Sciences - Immunology - Immunochemistry
Principal researcher:Denise Vilarinho Tambourgi
Grantee:Ana Tung Ching Ching
Home Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
Associated research grant:13/07467-1 - CeTICS - Center of Toxins, Immune-Response and Cell Signaling, AP.CEPID

Abstract

Bites by Loxosceles spiders can produce severe clinical symptoms, including dermonecrosis, thrombosis and haemolysis. Renal failure is one of the major causes of death after Loxosceles envenomation, and recently we have started to investigate the mechanism of renal dysfunction induced by Loxosceles venom. The sphingomyelinase D (SMase D) is the main factor in Loxosceles spider venom responsible for local and systemic manifestations.Serum therapy remains the only specific treatment against envenoming, including spider, but antivenoms are still prepared by fragmentation of polyclonal antibodies isolated from hyper-immunized horse serum. Most of these antivenoms are considered to be efficient, but their production is tedious, and their use may be associated with adverse effects. Recombinant antibodies and smaller functional units are now emerging as credible alternatives and constitute a source of still unexploited biomolecules capable of neutralizing venoms.New technologies have recently been applied leading to novel antibody formats with better properties in terms of specificity and avidity to enhance the antivenom efficacy. High-throughput sequencing of antibody repertoires offers the potential to study the humoral immune system in a quantitative and systems-based approach.Analyses of antibody-antigen binding are increasing and together with immunoglobulin sequencing data, using high-throughput next generation sequencing, will allow us to understand and examine antigen receptor repertoires at nucleotide sequence level. These valuable information on antibody-antigen interaction may contribute to new proposals for Loxosceles envenoming therapies, including the construction of high affinity antibodies against SMase D.

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