Anticomplementary activity of horse IgG and F(ab')2 antivenoms.
Envenomation by poisonous animals is a neglected condition according to the World Health Organization (WHO). Antivenoms are included in the WHO Essential Medicines List. It has been assumed that immunoglobulin G (IgG) antivenoms could activate the complement system through Fc and induce early adverse reactions (EARs). However, data in the literature indicate that F(ab')2 fragments can also activate the complement system. Herein, we show that several batches of IgG and F(ab')2 antivenoms from the Butantan, Vital Brazil, and Clodomiro Picado Institutes activated the complement classical pathway and induced the production of C3a; however, only those antivenoms from Clodomiro Picado generated C5a. Different protein profiles (IgG heavy chain, protein contaminants, and aggregates) were observed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and Western blot analyses. Our results show that various antivenoms from different producers are able to activate the classical pathway of the complement system and generate anaphylatoxins, and these findings suggest that factors, such as composition, contaminant proteins, and aggregates, may influence the anticomplementary activity of antivenoms in vitro. Therefore, there is a need to further improve antivenom production methods to reduce their anticomplementary activity and potential to cause EARs.
Laboratório de Imunoquímica, Instituto Butantan, São Paulo, SP, Brazil; Seção de Processamento de Plasmas Hiperimunes, Instituto Butantan, São Paulo, Brazil; Instituto Vital Brazil, Niterói, Brazil; Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica.
Carla Cristina
CC
Squaiella-Baptistão
José Roberto
JR
Marcelino
Luiz Eduardo
LE
Ribeiro da Cunha
José María
JM
Gutiérrez
Denise V
DV
Tambourgi
D000706:Anaphylatoxins; D000818:Animals; D000997:Antivenins / Q000494:pharmacology*; D015153:Blotting, Western; D003167:Complement Activation / Q000187:drug effects; D015926:Complement C3a / Q000096:biosynthesis / Q000187:drug effects; D015936:Complement C5a / Q000096:biosynthesis / Q000187:drug effects; D003171:Complement Pathway, Classical / Q000187:drug effects*; D003435:Crotalid Venoms; D004591:Electrophoresis, Polyacrylamide Gel; D006736:Horses; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology*; D007074:Immunoglobulin G / Q000494:pharmacology*; D007155:Immunologic Factors / Q000494:pharmacology*; D009500:Neutralization Tests; D011817:Rabbits; D012604:Scorpion Venoms; D012756:Sheep
D000706:Anaphylatoxins; D000997:Antivenins; D003435:Crotalid Venoms; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D007155:Immunologic Factors; D012604:Scorpion Venoms; D015926:Complement C3a; D015936:Complement C5a