The use of certain drugs during surgery can result in anaphylactic shock, and the exacerbated allergic reaction is explained in 80% or more of those cases by the presence of antidrug antibodies of the immunoglobulin E (IgE) class. The cause has been a mystery, however, in the 10% to 20% of cases where evidence for the involvement of antidrug IgE is lacking, according to a report in Science Translational Medicine. Antidrug IgE enables activation of mast cells and basophils that release histamine, which can lead to anaphylaxis.

Now, French researchers think they may have found the answer. A study team involving the Institut Pasteur, Inserm, the Paris Public Hospital Network, the CNRS, Paris-Sud University, and Sorbonne University identified a new pathological mechanism responsible for the unexplained cases: neutrophils activated by antibodies of the immunoglobulin G (IgG) class.

“Although IgG antibodies are known to protect the body from infection and to act as aggressors in some autoimmune diseases, this study reveals that they may be involved in humans in another reaction that is harmful for the body, anaphylaxis,” pointed out coauthor Pierre Bruhns, PhD, Inserm Research Director and Head of the Institut Pasteur’s Antibodies in Therapy and Pathology Unit. “We are currently carrying out experimental research to explore how we might block this new activation pathway for IgG antibodies so that we can propose a therapeutic solution.”

For the study, the researchers focused on allergic reactions to neuromuscular blocking agents (NMBAs), which are drugs used during general anesthesia to induce muscle relaxation. An estimated 1 out of every 10,000 to 20,000 surgeries results in anaphylactic shock caused by NMBAs, according to background information in the report.

The study team monitored 86 patients with perioperative anaphylactic shock and 86 control patients in 11 hospitals in the Greater Paris area. Blood samples were drawn as soon as anaphylactic shock occurred in the surgery suites, which allowed the researchers to identify the alternative IgG-dependent mechanism.

The study explained that IgG antibodies activate neutrophils and that concentrations of anti-NMBA IgG and markers of Fc gamma receptor activation, platelet-activating factor release, and neutrophil activation correlated with anaphylaxis severity. The IgG-neutrophil pathway was also identified in most cases of shock in which the traditional IgE-dependent mechanism was observed, according to the authors, who posited that the two mechanisms might work together to increase the severity of many cases of anaphylaxis.

“These findings elucidate 10 to 20% of cases of anaphylactic shock that previously had no biological explanation. They will be extremely valuable in refining diagnosis in these patients and avoiding any future exposure with the drug that triggered the allergic reaction,” suggested coauthor Sylvie Chollet-Martin, MD, PhD, of Paris-Sud University and head of the Immunology laboratory on Autoimmunity and Hypersensitivity at Bichat Hospital.

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