The phenotype of allergic diseases associated with Anisakis determines the pattern of cytokines related to antibody production. However, the role of serum IgA and the immunomodulatory mechanisms exerted by active infection of L3 or passive mucosal contact with A. simplex specific antigens has not been studied before. We measured serum cytokine by flow cytometry (IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ, IL-17A, TGF-β1) and antibody levels (IgE, IgG4, IgA) by ELISA against total and excretory-secretory (ES) antigens, Ani s 3,and the group of major allergens Ani s 1, Ani s 7, and Ani s 13 in sera from 10 patients with gastro-allergic anisakiasis (GAA), 11 Anisakis sensitization associated chronic urticaria (CU+) as well as 17 non-Anisakis-sensitized patients with chronic urticaria (CU-), compared with the urticaria control group (18 subjects). Specific IgE, IgG4 and IgA were high in the GAA, but IgA levels were significantly higher in the CU+ with respect the CONTROL group. We observed higher levels of the ratio IgA/IgG4 in CU+ than GAA group for Ani s 1, Ani s 7, Ani s 13 and ES. Furthermore, chronic urticaria (CU) patients showed significant lower levels of IL-10, IFN-γ and IL-17A than patients without CU. The anti-Ani s 13 IgA/IgG4 ratio correlated positively with pro-inflammatory cytokines and ratios (TNF-α, IL-17A, Th17/Th2, Type1/Type2 and TNF-α/IL-10) in CONTROL group. In general, Anti-Anisakis IgA/G4 ratio was high in CU patients. In conclusion, this study demonstrates the importance of serum IgA because it is associated with chronic urticaria independently of Anisakis sensitization.

BACKGROUND: Anisakis simplex (A. simplex) infection, in humans, causes a series of clinical manifestations affecting the gastro-intestinal tract known as Anisakiasis/Anisakidosis. Patients may also present allergic manifestations such as hives and/or angioedema and even anaphylactic shock. The aim of this study was to investigate whether aquacultured fish could be considered A.simplex-free food and constitute a safe, alternative, wild-capture fish food for Gastro-Allergic Anisakiasis (GAA)-sensitized subjects.
METHODS: Protein extracts from A. simplex larvae in the third stage (L3) and from edible part of heavily infected horse mackerel (Trachurus trachurus) and aquacultured sea bream, have been tested for A. simplex allergens presence by immunological analysis. Western blot analysis using, as source of specific Anisakis allergens antibodies, serum samples from subjects referring allergic symptoms after raw fish ingestion, was performed. These subjects showed high levels of specific IgE anti A.simplex allergens determined by clinical laboratory tests (ISAC test).
RESULTS: Our data demonstrate the presence of Ani s4 allergen in both infected and aquacultured fish extracts, providing a possible interpretation for the allergic manifestations reported by subjects, already sensitized to A. simplex, who ate frozen or well-cooked or, even, aquacultured fish.
CONCLUSIONS: The present data stimulate more accurate prophylaxis suggestions for Anisakis allergy and more specific controls of fishmeal used in aquaculture.

BackgroundAnisakiasis is an emerging zoonosis caused by the fish parasitic nematode Anisakis infecting the gastrointestinal tract. Case presentationWe describe a case of a 58-year-old woman diagnosed with gastro-allergic anisakiasis, in which the patient developed an acute food-induced IgE-mediated hypersensitivity reaction as well as concurrent gastro-intestinal manifestations after consumption of raw fish. The patient presented with epigastric pain, anaphylaxis and acute dysphagia caused by eosinophilic oesophagitis. DiscussionAnisakis allergy should be considered as causative agent in patients presenting with acute urticarial rash, anaphylaxis and/or abdominal manifestations, especially when symptoms occur after consumption of seafood. Moreover, eosinophilic oesophagitis may be a rare but important complication of Anisakis infection. Endoscopic evaluation with esophageal biopsies should therefore be considered if suggestive symptoms are present. Patients with confirmed gastroallergic anisakiasis are advised to properly freeze or cook fish prior to consumption, although caution is advised, since heat-stable allergen proteins have been described. An adrenaline auto-injector should be prescribed.