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This article provides an allergological reappraisal of the Annex to the European Commission guideline on excipients in medicinal products. The authors argue that the current guideline is outdated and fails to include excipients that have been reported to cause severe hypersensitivity reactions. They stress the importance of updating allergological information on excipients to ensure patient safety. The article includes tables summarizing excipients not included in the guideline and examples of reported hypersensitivity reactions. The document also provides a list of various substances and their associated adverse reactions, highlighting the need to update the allergological information of certain excipients in the Annex. The authors declare no conflicts of interest and received no funding for the study. [Extracted from the article]

Background: Anisakiasis is a re-emerging global disease caused by consumption of raw or lightly cooked fish contaminated with L3 Anisakis larvae. This zoonotic disease is characterized by severe gastrointestinal and/or allergic symptoms which may misdiagnosed as appendicitis, gastric ulcer or other food allergies. The Anisakis allergen Ani s 5 is a protein belonging to the SXP/RAL-2 family; it is detected exclusively in nematodes. Previous studies showed that SXP/RAL-2 proteins are active antigens; however, their structure and function remain unknown. The aim of this study was to elucidate the three-dimensional structure of Ani s 5 and its main IgE and IgG4 binding regions. Methodology/Principal Findings: The tertiary structure of recombinant Ani s 5 in solution was solved by nuclear magnetic resonance. Mg2+, but not Ca2+, binding was determined by band shift using SDS-PAGE. IgE and IgG4 epitopes were elucidated by microarray immunoassay and SPOTs membranes using sera from nine Anisakis allergic patients. The tertiary structure of Ani s 5 is composed of six alpha helices (H), with a Calmodulin like fold. H3 is a long, central helix that organizes the structure, with H1 and H2 packing at its N-terminus and H4 and H5 packing at its C-terminus. The orientation of H6 is undefined. Regarding epitopes recognized by IgE and IgG4 immunoglobulins, the same eleven peptides derived from Ani s 5 were bound by both IgE and IgG4. Peptides 14 (L40-K59), 26 (A76-A95) and 35 (I103-D122) were recognized by three out of nine sera. Conclusions/Significance: This is the first reported 3D structure of an Anisakis allergen. Magnesium ion binding and structural resemblance to Calmodulin, suggest some putative functions for SXP/RAL-2 proteins. Furthermore, the IgE/IgG4 binding regions of Ani s 5 were identified as segments localized on its surface. These data will contribute towards a better understanding of the interactions that occur between immunoglobulins and allergens and, in turn, facilitate the design of novel diagnostic tests and immunotherapeutic strategies. Author Summary: Knowledge of potential pathogens in seafood is of major significance for human health. The high rates of parasitation of fish all over the world make Anisakis a serious health hazard. In fact, Anisakiasis is a growing zoonotic disease in countries where consumption of raw/marinated fish is high. Moreover, Anisakiasis could be under diagnosed in countries where the consumption of these dishes is less common, since it could be easily misdiagnosed as appendicitis, gastric ulcer or other food allergies. Allergen structural studies are essential for the development of specific diagnostic tests and novel immunotherapy strategies. In the present study, we have elucidated for the first time the tertiary structure of Ani s 5 Anisakis allergen and its IgE and IgG4 regions implicated in allergic response. Ani s 5 belongs to the SXP/RAL-2 protein family. Several members of this family have been detected in animal and plant parasitic nematodes. As no homologs have been identified outside the Nematoda, these proteins may be suitable targets for controlling the damage caused by these parasites. Our work reveals that the structure of Ani s 5 resembles that of Calmodulin but binds Mg2+ instead of Ca2+, which suggests some putative functions for SXP/RAL-2 proteins. [ABSTRACT FROM AUTHOR]

Background: Anisakiasis is a re-emerging global disease caused by consumption of raw or lightly cooked fish contaminated with L3 Anisakis larvae. This zoonotic disease is characterized by severe gastrointestinal and/or allergic symptoms which may misdiagnosed as appendicitis, gastric ulcer or other food allergies. The Anisakis allergen Ani s 5 is a protein belonging to the SXP/RAL-2 family; it is detected exclusively in nematodes. Previous studies showed that SXP/RAL-2 proteins are active antigens; however, their structure and function remain unknown. The aim of this study was to elucidate the three-dimensional structure of Ani s 5 and its main IgE and IgG4 binding regions. Methodology/Principal Findings: The tertiary structure of recombinant Ani s 5 in solution was solved by nuclear magnetic resonance. Mg2+, but not Ca2+, binding was determined by band shift using SDS-PAGE. IgE and IgG4 epitopes were elucidated by microarray immunoassay and SPOTs membranes using sera from nine Anisakis allergic patients. The tertiary structure of Ani s 5 is composed of six alpha helices (H), with a Calmodulin like fold. H3 is a long, central helix that organizes the structure, with H1 and H2 packing at its N-terminus and H4 and H5 packing at its C-terminus. The orientation of H6 is undefined. Regarding epitopes recognized by IgE and IgG4 immunoglobulins, the same eleven peptides derived from Ani s 5 were bound by both IgE and IgG4. Peptides 14 (L40-K59), 26 (A76-A95) and 35 (I103-D122) were recognized by three out of nine sera. Conclusions/Significance: This is the first reported 3D structure of an Anisakis allergen. Magnesium ion binding and structural resemblance to Calmodulin, suggest some putative functions for SXP/RAL-2 proteins. Furthermore, the IgE/IgG4 binding regions of Ani s 5 were identified as segments localized on its surface. These data will contribute towards a better understanding of the interactions that occur between immunoglobulins and allergens and, in turn, facilitate the design of novel diagnostic tests and immunotherapeutic strategies. [ABSTRACT FROM AUTHOR]

Background: Although cross-reactivity with other plant-based foods and latex has been described, allergies to potatoes and tomatoes are uncommon., Objective: To study the different sensitization patterns in patients who are allergic to potatoes and/or tomatoes., Methods: Skin prick tests were carried out with fresh foods and extracts, specific IgE determination and allergen detection by SDS-PAGE and IgE-Immunoblotting with both raw and heated potato and tomato extracts., Results: In 10 patients, two thermostable allergens to potato extract were detected; the first one with a molecular weight that is compatible with Sola t 1 (43 kDa, patatin) and the second one with a molecular weight of 14-22 kDa, which could correspond to the allergens Sola t 4 (16 kDa) and Sola t 2 and Sola t 3 (21 kDa); in two patients who are allergic to potatoes and two patients who are allergic to tomatoes, a thermostable allergen that is compatible to Sola I 2 (50 kDa) was detected. The patient had presented oral allergy syndrome with some types of potatoes and showed higher IgE reactivity to two thermostable potato allergens., Conclusions: The allergen sensitization patterns were similar in all the patients that had been studied, regardless of the symptoms. A new allergen involved in the allergy to solanaceae plants has been detected.

Finding evidence of anisakidosis requires invasive methods. We have developed a serological assay based on the detection of an immunoglobulin E (IgE) specifically directed against Ani s 1 protein, a major parasite allergen of Anisakis simplex, which has shown a high level of accuracy in the diagnosis of anisakidosis. We used this tool to determine the prevalence of anti-Ani s 1 IgE in dyspeptic patients and to investigate if its seropositivity could be related to epidemiological factors other than raw fish consumption. A total of 174 dyspeptic patients who submitted to upper digestive tract endoscopy were studied. Specific IgE against Ani s 1 was determined by immunoblotting. Quantitative information on smoking, alcohol consumption, and fish consumption as well as a history of gastric surgery was recorded. Twenty-four (13.8%) patients were seropositive for Ani s 1 protein. The seroprevalence of anti-Ani s 1 IgE increased with age in patients who were less than 62 years old (P = 0.047). Seropositivity to Ani s 1 was associated with the consumption of fish in vinegar (P < 0.001), raw fish (P = 0.001), and smoked fish (P = 0.007). There was no relationship between anti-Ani s 1 IgE seropositivity and the number of cigarettes smoked (P = 0.098) or alcohol intake (P = 0.179). Five patients had undergone previous gastric surgery, and three of those patients were seropositive for Ani s 1 (P = 0.019). In multivariate analysis, the consumption of fish in vinegar (P = 0.006), raw fish (P = 0.017), and smoked fish (P = 0.002) and a history of gastric surgery (P = 0.005) were independent factors associated with anti-Ani s 1 IgE detection. In conclusion, at present, anisakidosis might frequently be underdiagnosed, and it might have a clinical role in patients with upper dyspeptic symptoms. Uncooked-fish ingestion and previous gastric surgery were associated with seropositivity for Ani s 1 protein.

Background and Objective: Infection by anisakid nematodes is associated with consumption of raw fish. The aim of this paper was to determine the prevalence of sensitization among members of families of patients with anisakiasis., Individuals and Methods: Eleven asymptomatic members of families of patients diagnosed with anisakiasis were studied by means of IgE-immunoblotting. The frequency of sensitization was compared with the prevalence in a normal population from the same geographic area., Results: A very high frequency of sensitization was observed among patients' family members (73%) as compared with the prevalence in normal population (12%) (p < 0.001)., Conclusion: All members of the family of a patient diagnosed with anisakiasis should be studied to determine whether they are sensitized.