Anticomplementary activity of equine whole IgG antivenoms: comparison of three fractionation protocols.
Abstract: Early adverse reactions occur in a number of patients treated with heterologous antivenoms and have been associated with anticomplementary activity (ACA). In order to reduce the ACA of equine whole IgG antivenoms produced by caprylic acid fractionation, three different fractionation protocols were compared: (a) routine caprylic acid fractionation; (b) caprylic acid fractionation followed by beta-propiolactone treatment; and (c) caprylic acid fractionation followed by ion-exchange chromatography using a quaternary ammonium membrane. The three protocols yielded products with similar physicochemical characteristics and anti-Bothrops asper venom antibody titers, except that ion-exchange purified antivenom had a lower protein concentration. Antivenoms fractionated by using beta-propiolactone or filtration through quaternary ammonium membrane had a significantly reduced in vitro ACA. A preparation of caprylic acid-fractionated antivenom was heated in order to induce the formation of protein aggregates; however, its ACA was similar to non-heated antivenom. None of the antivenoms affected the hemolytic activity of serum complement in rabbits after a bolus intravenous administration. It is concluded that (a) beta-propiolactone and quaternary ammonium membranes significantly reduce in vitro ACA of caprylic acid-fractionated equine antivenom, and (b) the validity of in vitro ACA as a predictor of EAR needs to be reexamined in clinical and experimental studies, since it may not adequately predict in vivo complement activation by antivenoms.
Publication Date: 2004-12-08 PubMed ID: 15581691DOI: 10.1016/j.toxicon.2004.07.025Google Scholar: Lookup
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- Comparative Study
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research article focuses on reducing adverse reactions in patients treated with antivenoms using various fractionation methods. It specifically looks at anticomplementary activity (ACA) of equine whole IgG antivenoms produced by caprylic acid fractionation and compares three fractionation methods.
Overview of the Study
- The researchers explored the anticomplementary activity of equine whole IgG antivenoms. In understanding antivenom production, they ultimately aim to reduce early adverse reactions in patients treated with heterologous antivenoms that are commonly associated with anticomplementary activity.
Comparison of Fractionation Protocols
- The study compared three different antivenom processing, or fractionation procedures. The fractionation methods include routine caprylic acid fractionation; caprylic acid fractionation followed by beta-propiolactone treatment; and caprylic acid fractionation carried through ion-exchange chromatography using a quaternary ammonium membrane. These three methods were compared to determine if there were significant disparities in the ACA of the antivenom produced.
Outcome of the Fractionation Protocols
- Following the comparison, the three protocols showed reversed products with comparable physicochemical characteristics and anti-Bothrops asper venom antibody titers. Ion-exchange purified antivenom, however, had a lower protein concentration.
- Antivenoms fractionated using beta-propiolactone or filtration through a quaternary ammonium membrane demonstrated a significant reduction in in vitro ACA.
Impact of Changes to Antivenom Preparation
- As a part of the study, a preparation of caprylic acid-fractionated antivenom was heated to induce the formation of protein aggregates. Regardless, its ACA remained similar to the non-heated antivenom. The hemolytic activity of serum complement in rabbits remained unaffected after a bolus intravenous administration of any of the antivenoms.
Conclusion
- From the study, it was concluded that beta-propiolactone and quaternary ammonium membranes significantly decrease the in vitro ACA of caprylic acid-fractionated equine antivenom.
- Furthermore, the validity of in vitro ACA as a predictor of early adverse reactions should be reevaluated in clinical and experimental studies. In vitro ACA measurements may not accurately predict in vivo complement activation by antivenoms.
Cite This Article
APA
León G, Lomonte B, Gutiérrez JM.
(2004).
Anticomplementary activity of equine whole IgG antivenoms: comparison of three fractionation protocols.
Toxicon, 45(1), 123-128.
https://doi.org/10.1016/j.toxicon.2004.07.025 Publication
Researcher Affiliations
- Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica.
MeSH Terms
- Animals
- Antivenins / adverse effects
- Antivenins / chemistry
- Antivenins / isolation & purification
- Caprylates
- Chemical Fractionation / methods
- Complement Activation / drug effects
- Crotalid Venoms
- Erythrocytes / drug effects
- Horses
- Humans
- Immunoglobulin G
- Ion Exchange
- Propiolactone
- Rabbits
- Sheep
Citations
This article has been cited 4 times.- Vanuopadath M, Rajan K, Alangode A, Nair SS, Nair BG. The Need for Next-Generation Antivenom for Snakebite Envenomation in India.. Toxins (Basel) 2023 Aug 18;15(8).
- Kurtović T, Lang Balija M, Brgles M, Sviben D, Tunjić M, Cajner H, Marchetti-Deschmann M, Allmaier G, Halassy B. Refinement strategy for antivenom preparation of high yield and quality.. PLoS Negl Trop Dis 2019 Jun;13(6):e0007431.
- Li B, Dong M, De J, Ye L, Chen D, Lu Y. Structural Characterization and Anti-Proliferation Activities Against Tumor Cells of an Arabinogalactan from Juniperus convallium.. Molecules 2019 May 14;24(10).
- Khamehchian S, Zolfagharian H, Dounighi NM, Tebianian M, Madani R. Study on camel IgG purification: a new approach to prepare Naja Naja Oxiana antivenom as passive immunization for therapy.. Hum Vaccin Immunother 2014;10(6):1633-8.
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