Complement activation by human IgG antibodies to galactose-alpha-1,3-galactose.

Complement activation by human IgG antibodies to galactose-alpha-1,3-galactose. Immunology. 2020 Jun 24;: Authors: Bernth Jensen JM, Laursen NS, Kjeldsen Jensen R, Andersen GR, Jensenius JC, Skov Sørensen UB, Thiel S Abstract Some human antibodies may paradoxically inhibit complement activation on bacteria and enhance pathogen survival in humans. This property was also claimed for IgG antibodies reacting with terminal Galα3Gal (IgG anti-αGal), a naturally occurring and abundant antibody in human plasma that targets numerous different pathogens. To reinvestigate these effects, we utilised IgG anti-αGal affinity isolated from a pool of normal human IgG and human hypogammaglobulinemia serum as a complement source. Flow cytometry was performed to examine antibody binding and complement deposition on pig erythrocytes, Escherichia coli O86, and Streptococcus pneumoniae serotype 9V. Specific nanobodies were used to block the effect of single complement factors and to delineate the complement pathways involved. IgG anti-αGal was found capable of activating the classical complement pathway on all the tested target cells. The degree of activation was exponentially related to the density of bound antibody on E. coli O86 and pig erythrocytes, but more linearly on S. pneumoniae 9V. The alternative pathway of complement amplified complement deposition. Deposited C3 fragments covered the activating IgG anti-αGal, obstructing its detection and...
Source: Immunology - Category: Allergy & Immunology Authors: Tags: Immunology Source Type: research