Abundant human anti-Galα3Gal antibodies display broad pathogen reactivity

Antibodies of the IgG class to terminal Gal alpha 3Gal (IgG anti-alpha Gal) is abundant in human plasma and are reported to bind most sepsis-causing Gram-negative bacteria. However, these seminal findings, made more than two decades ago, have not been reexamined. Our aim was to assess IgG anti-alpha Gal ' s pathogen reactivity. We affinity purified IgG anti-alpha Gal from a therapeutic grade normal human IgG pool applying two rounds of positive selection with Gal alpha 3Gal-coupled beads and included removal of column matrix reactive antibodies. The purified antibodies were rigorously characterized in terms of specificity and purity in various solid-phase immunoassays. We used flow cytometry to study reactivity against 100 consecutive clinical isolates diagnosed as cause of sepsis in humans. We found that the purified IgG anti-alpha Gal displays high specificity for Gal alpha 3Gal. Also, IgG anti-alpha Gal at 5mg/L bound 56 out of 100 pathogens with predilection for Gram-positive bacteria binding 39 out of 52 strains. We confirm that although IgG anti-alpha Gal comprise a small fraction of the human antibody pool (similar to 0.1%), these antibodies targets an impressively large part of pathogens causing invasive disease.