Insects have been proposed as a high quality, efficient and sustainable alternative protein source for humans and animals, and a vast selection of edible products is currently available in many European countries. However, respiratory allergy among professional and domestic breeders and food allergy among consumers are known. 1,2We here report the case of 2 patients (Pt#1 and Pt#2, both male, 24 and 27 years old, respectively) employed in the production of insect flour made of yellow mealworm larvae (Tenebrio molitor larvae, TML) and black soldier fly larvae (Hermetia illucens larvae, HIL).The patients did not show the previous history of food or respiratory allergies. In the same factory, a total of ten workers handled TML, eight out of ten without developing any symptom. The first symptoms of the 2 patients (rhinoconjunctivitis, itching and contact erythema) appeared after some weeks of repetitive exposure to TML. They did not report any symptoms when exposed to HIL.The symptoms were particularly severe during the sifting of TML from their faeces (TMF), and when the patients entered the rearing room after the sifting operation, they disappeared after 24 hours.The sensitization therefore presumably occurred through a percutaneous route and/or by inhalation. After developing symptoms, Pt#1 continued to work using adequate protection devices, while Pt#2 left the job. The 2 patients were used to eat such edible insects as the greater wax moth, crickets and HI. They experienced an oral allergy syndrome (OAS) characterized by oral pruritus and tightness in the throat, as soon as they start eating for the first time a TML hamburger. Symptoms recovered spontaneously in about 40 minutes. Following this episode, they continued to tolerate other edible insects, but never tried to taste TML again and refused to undergo provocation test.In order to characterize the patients' allergic profile, we performed: skin prick tests (SPTs) with a standard battery of inhalant and food allergens, specific IgE for TM, Der p10, Dermatophagoides pteronyssinus, Dermatophagoides farinae and Prawn (ImmunoCap Thermo Fisher Scientific Inc) and basophil activation test (BAT) with TML and TMF protein extracts. Immunoblot analyses of both protein extracts and LC-MS/MS analysis followed by protein database screening were performed in order to identify the allergens involved in the TM sensitization (see Appendix S1).The SPTs with inhalant and food allergens were negative in both patients, except for Grass in Pt#1 and Alternaria in Pt#2. Specific TM IgEs were present in both patients (21.00 and 10.63 kU A /L, respectively), while no specific IgEs were found for house dust mites, Prawn and Der p10. BAT were positive in both subjects for TMF and TML (Figure 1).Immunoblotting showed a 15 kDa reactive band in both the TML and TMF extracts, when incubated with both patients' sera ( Figure 2, panel A). Three additional aspecific bands were also detected in the healthy control patients' serum pool, but only in the TML extract ( Figure 2). The cockroach all...