Safety of uSCIT-MPL-4: prevalence and risk factors of systemic reactions in real life

Aim: We assessed the safety of allergoid adjuvanted by monophosphoryl lipid A (uSCIT-MPL-4) in a real-life setting. Materials & methods: Patients treated with uSCIT-MPL-4 were followed-up for 1 year. Systemic reactions (SRs) were registered and the association with potential risk factors was evaluated. Results: 2929 patients were included. Grade 0, 1, 2, 3 and 4 SR reactions were observed respectively in 3.3, 1.5, 0.31, 0.07 and 0.07% of patients. A significant association was detected between Grade >= 1 SRs and: female gender, number of administrations, previous local reactions. Conclusion: uSCIT-MPL-4 is safe. Local reactions should be accurately assessed as they may represent a risk factor for Grade >= 1 SRs, together with gender and number of doses/year

The paradox of Bcl-2: How does paclitaxel convert Bcl-2 function from antiapoptotic to proapoptotic?

Bcl-2 is an antiapoptotic protein often overexpressed in human cancer and exerts an antiapoptotic function at mitochondrial level, through the opening suppression of the permeability transition pore complex (PTPC). This process prevents the consequent leakage of mitochondrial transmembrane potential and effluxing from mitochondria of proapoptotic factors such as Cytochrome C, AIF and APAF-1. Recently, in ovarian cancer cells paclitaxel (PTX)-resistance has been associated to downregulation of Bcl-2. In order to investigate this paradox, human Bcl-2 was stably transfected in PTX-resistant ovarian cancer cells and mitochondria were isolated from these cells. Mitochondria prepared from untransfected control cells showed undetectable levels of Bcl-2 and PTX was unable to modulate the opening of PTPC, as demonstrated by the uptake of the cationic fluorochrome Rhodamine 123. In the same cells transfected with Bcl-2, sensitivity to paclitaxel was restored and the drug was able to induce the opening of PTPC and the leakage of mitochondrial transmembrane potential. Among Bcl-2 family members, the peculiar difference of Bcl-2 consists in the disordered loop domain. Therefore, we prepared stable Bcl-2 transformed cells with a construct devoid of the loop domain (Bcl-2-Δ). In mitochondria prepared from these cells, PTX was unable to modulate the opening of PTPC. These findings suggest that the disordered loop of Bcl-2 is involved in the PTX binding, but did not clarify if this occurs in a direct or indirect way, with the involvement of other proteins. In order to address this issue, we used plasmon resonance-based optical biosensor technology. In vitro Bcl-2 and Bcl-2-Δ translated proteins were immobilised on a optical biochip to permit a real time monitoring of the potential binding of paclitaxel to Bcl-2. The experimental output pointed out that PTX directly binds to Bcl-2, and not to Bcl-2-Δ, this signaling that the PTX binding site is located within the disordered loop domain of the protein. With the aim of better understanding the binding mechanism, we performed molecular modelling investigations, taking as template the experimentally determined structure of class I beta-tubulin in complex with PTX. Results indicated that the putative binding site of PTX in the disordered loop domain is indeed very similar to that present in beta tubulin. In beta-tubulin PTX binds to a pocket with strong interactions with His229, Pro360-Pro359 and the sequence Arg278-Ser277-Thr276-Leu275-Pro274. Similar interactions were found in our paclitaxel/Bcl-2 docked complex: His58, Pro39-Pro40 and the sequence Thr69-Arg68-Ala-67-Val66-Pro65. Due to the similarity in the binding, it is likely that PTX is a peptide-mimicking structure with a structure similar to endogenous agonist(s) able to bind to both beta-tubulin and Bcl-2, and consequently transferring a death signal from microtubules to mitochondria

How far from correct is the use of adrenaline auto-injectors? A survey in Italian patients

Self-administered adrenaline through an auto-injector is the main out-of-hospital treatment for anaphylaxis, and patients should be trained to promptly and correctly use the device. The aim of the study was to verify the proper use of the device and the correct drug administration, and to identify possible misuse by patients. In seven Italian Allergy clinics, patients who were previously provided with self-injectable adrenaline were recruited at the follow-up visit required for the renewal of their prescription. All patients completed a questionnaire covering details of their allergic reactions, and knowledge of the device. The correct use was verified by the physician using a trainer with a four-step examination. 242 patients were included; 46 patients (18 %) did not always carry the auto-injector, and 35 patients (14 %) reported situations in which they were doubtful about whether to use adrenaline. Only 39 % of patients properly managed the device, while some patients (6 %) failed in all four steps. The majority of patients considered it appropriate to use adrenaline at the onset of respiratory symptoms (56 %). The factor most closely related to proper use of the device was the education of the patient (p = 0.03), while age and the time from first prescription did not affect the ability to properly use the auto-injector. Even though accurate training is conducted, many patients are still unable to properly use the adrenaline auto-injector in case of anaphylaxis. Allergists should review the instructions provided to the patients every time a renewal of the auto-injector is prescribed

Systemic allergic reactions induced by labile plant‐food allergens: Seeking potential cofactors. A multicenter study

Background: Heat-and-pepsin-sensitive plant food allergens (PR-10 and profilin) sometimes cause systemic reaction.Objective: To detect the risk factors for systemic reactions induced by labile food allergens.Methods: A retrospective multicenter study was performed on patients with a documented history of systemic allergic reaction to labile plant food allergens and on age-matched controls with a history of oral allergy syndrome (OAS) induced by the same foods. Offending foods, their amount, and state (solid or liquid), and potential cofactors (nonsteroidal anti-inflammatory drugs, protonic pump inhibitors, exercise, alcohol, and fasting) were considered.Results: We studied 89 patients and 81 controls. Sensitization to PR-10 or profilin, IgE to Bet v 1 and/or Bet v 2, and foods causing OAS were similar in the two groups. Twenty patients experienced >1 systemic allergic reaction. Tree nuts, Rosaceae, Apiaceae, and soymilk were the main offending foods. Seventeen (19%) patients were taking a PPI when the systemic reaction occurred (vs 5% in controls; P < .025). The ingestion of the offending food in liquid form (soymilk) was frequent among patients (15%) but unusual among controls (2%; P < .025). Soy milk-induced systemic reactions were independent of PPI treatment. Fasting and excess of allergen, but not NSAID and exercise, were other relevant cofactors for systemic reactions. Systemic reactions occurred without any identifiable cofactor in 39 (44%) cases.Conclusion: PR-10- and profilin-induced systemic reactions are facilitated by PPI, ingestion of large amounts of unprocessed foods, and fasting. Soybean beverages represent a risk for PR-10 hypersensitive patients and should be avoided

Mollusk allergy in shrimp-allergic patients: Still a complex diagnosis. An Italian real-life cross-sectional multicenter study

Introduction: Shellfish allergy is an important cause of food allergies worldwide. Both in vivo and in vitro diagnostics failure nowadays is caused by the poor quality of the extracts associated with the scarce availability of allergenic molecules in the market. It is known that not all patients with shellfish allergies experience adverse reactions to mollusks. It is still unclear how to detect and diagnose these patients correctly.Aim: To investigate the features of shrimp-allergic patients either reactive or tolerant to mollusks, with the currently available diagnostic methods.Methods: Nineteen centers, scattered throughout Italy, participated in the real-life study, enrolling patients allergic to shrimp with or without associated reactions to mollusks. Patients underwent skin tests using commercial extracts or fresh raw and cooked shrimp and mollusks, and IgE reactivity to currently available allergenic extracts and molecules was measured in vitro.Results: Two hundred and forty-seven individuals with a self reported adverse reactions to shrimp participated in the study; of these 47.8% reported an adverse reaction to mollusks ingestion (cephalopod and/or bivalve). Neither of the tests used, in vivo nor in vitro, was able to detect all selected patients. Accordingly, a great heterogeneity of results was observed: in vivo and in vitro tests agreed in 52% and 62% of cases. Skin tests were able to identify the mollusk reactors (p < 0.001), also using fresh cooked or raw food (p < 0.001). The reactivity profile of mollusk reactors was dominated by Pen m 1, over Pen m 2 and Pen m 4 compared to tolerant subjects, but 33% of patients were not detected by any of the available molecules. Overall, a higher frequency of IgE rectivity to shrimp was recorded in northern Italy, while mollusk reactivity was more frequent in the center-south.Conclusion: The current diagnostic methods are inadequate to predict the cross-reactivity between crustaceans and mollusks. The detection of mollusks hypersensitivity should still rely on skin tests with fresh material. The exclusion of mollusks from shrimp allergic patients' diets should occur when clinical history, available diagnostic instruments, and/or tolerance tests support such a decision

House dust mite allergy in Italy. Diagnostic and clinical relevance of Der p 23 (and of minor allergens): A real life, multicenter study

House dust mites (HDM) area major cause of respiratory allergy and of perennial asthmaworldwide. 32 allergens for Dermatophagoidesfarinae(D2) and 21 for Dermatophagoides pteronyssinus(D1) have been detectedso farand novel allergens are still being reported(1). Der p 23, a gut-derived peritrophin present in the outer membrane of mite feces (2),has been recognized as a major allergen (2,3).Der p 1, Der p 2, Der p 23, and Der p 10(tropomyosin)are theonly allergens currently available for the component-resolved diagnosis of HDMallergyon ImmunoCAP.The clinical relevance of Der p 23 is only partially defined, and the prevalence and relevance of the exclusive sensitization to allergensother than groups1, 2, 10, and 23 has received little attention so far. We addressed these aspects ina large multicenter study