Pointreau Y, Freneaux C, Bejan-Angoulvant T, Ternant D, Calais G, et al.
Immuno-oncology technology •
Fatal anaphylactic reactions to cetuximab remain a clinical issue, although they are associated with preexisting immunoglobulin E (IgE) directed against the galactose-α1,3-galactose epitope (α3Gal). We aimed to compare the clinical usefulness of the two assays and determine the prevalence of preexisting anti-α3Gal IgE. An anti-α3Gal IgE assay was developed (70BP assay) and compared with a commercial assay [bovine thyroglobulin (bTG) assay]. Both assays were applied to two cohorts: 299 healthy blood donors and 41 patients with head and neck cancer treated with cetuximab, including four patients with a history of anaphylactic reaction (9.8%). The prevalence of anti-α3Gal IgE was 6% and 5% using 70BP and bTG assays, respectively, in healthy blood donors. Among the head and neck cancer patients, the four who had an anaphylactic reaction were included in the seven (17.1%) and six (14.6%) patients with a signal above the detection threshold using the 70BP and bTG assays, respectively. This resulted in a sensitivity and negative predictive value of 100% for both assays, with a specificity of 91.9% and 94.6%, respectively, and a positive predictive value of 57.1% and 66.6% for the 70BP and bTG assays, respectively. Using an optimized threshold in the bTG assay, the prevalence of anti-α3Gal IgE in blood donors decreased to 1.3%, and five patients (12.2%) were eventually considered positive, giving a specificity of 97.3% and a positive predictive value of 80%. The predictive value of anti-α3Gal IgE using these two assays was excellent and useful in clinical practice.
Thorel M, Mateos-Hernandez L, Mulot B, Azzouni MN, Hodžić A, et al.
Frontiers in immunology •
Aspergillosis is a fungal infection caused mainly by that often results in respiratory disease in birds. Aspergillosis is a major cause of morbidity and mortality in captive-bred penguin species. Currently, there is no registered vaccine to prevent aspergillosis. Recent research demonstrated that oral administration of gram-negative bacteria expressing high levels of galactose-α-1,3-galactose (α-Gal) modulates anti-α-Gal immunity and protects turkeys from clinical aspergillosis caused by experimental infection. The role of anti-α-Gal immunity in penguins has not been studied. Here, we tested the distribution of α-1,3-galactosyltransferase (α1,3GT) genes in the fecal microbiome of Humboldt penguins (). The occurrence of natural anti-α-Gal antibodies (Abs) in sera and eggs of healthy Humboldt penguins was also assessed. A trial was then conducted to test whether oral administration of Nissle, expressing high α-Gal levels, modulates anti-α-Gal immunity in a colony of Humboldt penguins. Animals in the vaccination and placebo groups were evaluated before the trial and followed for one year for aspergillosis detection using a diagnostic panel including computed tomography scans, capillary zone electrophoresis, 3-hydroxybutyrate levels, and anti- Abs. Anti-α-Gal Abs were detected in sera (IgM and IgY) and eggs (IgY) of healthy penguins. Microbiota analysis and functional predictions revealed the presence of α1,3GT genes in the microbiota of Humboldt penguins and other penguin species. A strong decrease in anti-α-Gal IgM levels was observed in all animals in the placebo group three months after vaccination protocol. This decrease was not observed in Nissle-treated penguins. After the vaccination protocol, we found a positive correlation between anti- IgY and anti-α-Gal IgY in the Nissle group, suggesting a correlation between the presence of the bacteria and these Abs. During the study period, three penguins exhibited respiratory signs consistent with aspergillosis. Two were from the placebo group whose symptoms resolved with specific treatments, while a single vaccinated individual developed fatal respiratory aspergillosis eight months after the trial. We conclude that Nissle represents a safe potential probiotic with a protective effect against aspergillosis in Humboldt penguins that deserves to be further explored for therapeutic uses in these animals.
The Charles Richet and Jules Héricourt workshops honor the memory of Jules Héricourt (1850-1938) and Charles Richet (1850-1935) who described the principle of serotherapy in 1888 and made the very first attempts to fight cancer with serotherapy in 1895. In 1902, Charles Richet and Paul Portier described "anaphylaxis," a discovery awarded the Nobel Prize in 1913. The first workshop, "Towards the clinical use of mAbs with higher cytolytic efficacy in cancer" was held in Tours, France on November 20-21, 2008. The second Charles Richet and Jules Héricourt workshop, held May 31-June 1, 2011 at the University of Tours, France, was also organized by the Cancéropôle Grand Ouest. The topic of the workshop was therapeutic antibodies and anaphylaxis, a subject rarely addressed in congresses focused on monoclonal antibodies. To have discussions about mAb side effects with complete objectivity, the congress was organized independently of any sponsorship from pharmaceutical companies. This academic event was motivated by the high incidence of shocks to cetuximab and the need to compile and evaluate scattered information. This growing public health concern was thus analyzed from different scientific and medical angles. The first session was devoted to acute infusion reactions, with an emphasis on deconvolution of the terms "cytokine-release syndrome," "cytokine storms," "anaphylaxis" and their epidemiology. This session concluded with the Charles Richet lecture on cetuximab anaphylaxis and anti-αGal IgE by Thomas Platts-Mills, its discoverer. In the next session, the involvement of anti-glycan antibodies in both anaphylaxis and delayed hypersensitivity reactions to therapeutic antibodies was discussed. A gala dinner was held in the gardens of the beautiful château of Villandry, which was acquired and restored by Joachim Carvalho, a pupil of Charles Richet's and great-grandfather of the present owner. The final session focused on strategies to prevent cetuximab anaphylaxis in clinical practice included a variety of topics, e.g., premedication, biobetters and biosimilars, skin testing and predictive assays. All speakers and attendees enjoyed this very stimulating and rewarding meeting, which gathered many people with divergent scientific backgrounds and medical specialties.
