Similar <scp>IgE</scp> binding patterns in Gulf of Mexico and Southeast Asian shrimp species in <scp>US</scp> shrimp allergic patients
Authors: Sara Anvari, Shea Brunner, Karen S. Tuano, Brenda Bin Su, Shaymaviswanathan Karnaneedi, Andreas L. Lopata, Carla M. Davis
Journal: Allergy (2022)

Shellfish allergy (SA) is a leading cause of food-induced anaphylaxis1 and one of the most common causes of adult-onset food allergy worldwide, with 1%–3% of the United States (US) population affected.2-4 Nearly half (45%) of US adults with SA report utilizing emergency services for SA symptoms over their lifetime,2 remaining at-risk for lethal allergic reactions. Several allergenic proteins have been identified across shellfish species, including tropomyosin (TM), arginine kinase (AK), myosin light chain (MLC), sarcoplasmic calcium-binding protein (SCP), hemocyanin, troponin C, and triosephosphate isomerase.5 (Table 1.) However, there are a large number of shrimp allergens that have been detected, but not yet characterized.6 The allergens of major importance in SA are the muscle proteins TM and AK. TM, the major allergen with specific-IgE antibodies in ≤90% of SA patients, is associated with severe clinical reactivity. AK is a pan-allergen with cross-reactivity with crustaceans and cephalopods.5 Cha f 1, Cra c 1, Hom a 1, Lit v 1, Mel l 1, Met e 1, Pan b 1, Pen m 1, Por p 1 Ingestion Inhalation Litopenaeus vannamei (White leg shrimp) Lit v Ingestion Inhalation Penaeus aztecus (Brown shrimp) Pen a Homarus americanus (American lobster) Hom a Crangon crangon (Sand shrimp) Cra c Charybdis feriatus (Crucifix crab) Cha f Ingestion Inhalation Portunus pelagicus (Blueswimmer crab) Por p Cross-reactivity has been observed clinically when SA patients ingest various invertebrate species with subsequent allergic reactions, but further study of shrimp sIgE binding between different shrimp species is needed.7, 8 This study examined the sIgE binding patterns to 2 shrimp species from the Gulf of Mexico and Southeast Asia in US SA patients. Shellfish allergy patients with a history of shrimp-induced allergic reactions, allergic reaction with clinical oral food challenge and positive immediate skin prick testing (IHST) and/or shrimp sIgE ImmunoCAP™ levels were recruited from the Baylor College of Medicine (BCM) Allergy and Immunology Clinics. The study was approved by the BCM IRB and all participants provided written, informed consent. The patients underwent IHST to shrimp extract (mixture of Penaeus borealis, Penaeus monodon, Metapenaeus barbata, and Metapenaeopsis joyner), Dermatophagoides pteronyssinus (Der p1, Der p 10), Dermatophagoides farinae (Der f1), cockroach, codfish, crab, lobster, and oyster using extracts from Greer™. The patients underwent prick and prick IHST to raw fresh shrimp (Penaeus aztecus), and cooked fresh shrimp (Penaeus aztecus). ImmunoCAP™ and ISAC™ customized testing by ThermoFisher™ assessed total IgE as well as sIgE levels for shrimp, recombinant Penaeus aztecus (TM), Der p10, Der p1, Der p2, recombinant Penaeus monodon AK, MLC, SCP, troponin C, crab, lobster, cockroach, clam, and oyster. Western blot (WB) analysis of sIgE binding profile to the major allergenic proteins TM, AK, MLC, and SCP in Penaeus aztecus (Brown shrimp) and Penaeus monodon (Black tiger shrimp) in raw and boiled extracts was performed. Fifteen SA patients between the ages of 2–17 years were enrolled. (Table 2) On oral food challenge, the most frequent symptoms were urticaria and angioedema. Forty percent had antihistamine treatment, one required steroids, and none required epinephrine or albuterol. When examining sIgE binding patterns to the major allergens, WB revealed nearly identical sIgE binding profiles to tropomyosin, MLC, and SCP in both species in the heated shrimp extracts. (Figure 1) Eight subjects (53%) demonstrated sIgE binding to TM and six to SCP (40%). There was variability in the binding to other shrimp proteins, particularly in the unheated shrimp.5 The proposed sIgE binding allergens have been identified by molecular weight,5, 6 and mass spectrometric in-gel analysis, (Table S1.) but need to be confirmed in future molecular studies.9, 10 The presence of Southeast Asian Black tiger shrimp sIgE has been established and quantified through ImmunoCAP™ ISAC™ testing, with over 50% of patients having binding to TM, 33% to SCP, 27% to AK, and 13% each to MLC and troponin C.6 Nevertheless, each individual patient's binding pattern in our study was similar between the two species, both unheated/raw (Figure 1A,B) and heated/boiled proteins (Figure 1C,D). Inhibitory immunoblot was performed which confirmed the identification of MLC and SCP. (Figure S1A,B) These similar sIgE binding patterns to the major allergens suggested conservation of the epitopes between different species of shrimp. According to the Food and Agricultural Organization of the United Nations, Penaeus aztecus is native to the north-western Atlantic Ocean and Gulf of Mexico, while Penaeus monodon is native to the coasts of Southeast Asia, South Asia, East Africa, and Australia. Our study demonstrates shared epitopes among the major shrimp proteins for Gulf Brown shrimp and Southeast Asian Black tiger shrimp in US shrimp allergic subjects, implicating shared diagnostic and therapeutic potential for SA to varied shrimp species. Sara Anvari, Contributed analysis tools, performed the analysis and wrote the paper. Shea Brunner, Contributed data, analysis tools and wrote the paper. Karen Tuano, Collected the data. Brenda Bin Su, Contributed analysis tools. Shaymaviswanathan Karnaneedi, Collected the data and performed analysis, and wrote the paper. Andreas L. Lopata, Conceived and designed analysis, performed the analysis and wrote the paper. Carla M. Davis, Conceived and designed analysis, collected data, and wrote the paper. We acknowledge funding from the National Institute of Allergy and Infectious Disease for this work. (1R34AI57948-01). Drs. Anvari and Davis receive research contract funding from DBV Technologies, Regeneron and Aimmune Therapeutics. Dr. Davis is a consultant for Moonlight Therapeutics and received grant funding from ThermoFisher Scientific. Dr Lopata received research contract funding from Aimmune Therapeutics. The other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Figure S1 Table SI Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. 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