Evidence of IgE-Mediated Cross-Reactions between Anisakis simplex and Contracaecum osculatum Proteins

Fish consumers may develop allergic reactions following the ingestion of fish products containing nematode larvae within the genus Anisakis. Sensitized patients may cross-react with proteins from insects, mites and mollusks, leading to allergic reactions even in the absence of the offending food. Potential cross-reactivity in Anisakis-allergic patients with larval proteins from other zoonotic parasites present in freshwater and sea fish should be investigated due to an increasing occurrence in certain fish stocks, particularly Contracaecum osculatum. In this work, we evaluated IgE-cross reactions by in vivo (skin prick tests with parasites extracts) and in vitro methods (IgE-ELISA and IgE-immunoblot). In vivo skin prick tests (SPT) proved the reactivity of Anisakis-sensitized patients when exposed to C. osculatum antigens. Sera from Anisakis-sensitized patients confirmed the reaction with somatic antigens (SA) and excretory/secretory proteins (ES) from C. osculatum. Only anecdotal responses were obtained from other freshwater worm parasites. Consequently, it is suggested that Anisakis-sensitized humans, especially patients with high levels of specific anti-Anisakis antibodies, may react to C. osculatum proteins, possibly due to IgE-mediated cross-reactivity.

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Analysis of the cross-reactivity and of the 1.5 Å crystal structure of the Malassezia sympodialis Mala s 6 allergen, a member of the cyclophilin pan-allergen family

Biochemical Journal ◽

10.1042/bj20051708 ◽

2006 ◽

Vol 396 (1) ◽

pp. 41-49 ◽

Cited By ~ 52

Author(s):

Andreas G. Glaser ◽

Andreas Limacher ◽

Sabine Flückiger ◽

Annika Scheynius ◽

Leonardo Scapozza ◽

...

Keyword(s):

Crystal Structure ◽

Three Dimensional ◽

Cross Reactivity ◽

Dimensional Structure ◽

Cellular Functions ◽

Human Proteins ◽

Ige Mediated ◽

Unit Cell Dimensions

Cyclophilins constitute a family of proteins involved in many essential cellular functions. They have also been identified as a panallergen family able to elicit IgE-mediated hypersensitivity reactions. Moreover, it has been shown that human cyclophilins are recognized by serum IgE from patients sensitized to environmental cyclophilins. IgE-mediated autoreactivity to self-antigens that have similarity to environmental allergens is often observed in atopic disorders. Therefore comparison of the crystal structure of human proteins with similarity to allergens should allow the identification of structural similarities to rationally explain autoreactivity. A new cyclophilin from Aspergillus fumigatus (Asp f 27) has been cloned, expressed and showed to exhibit cross-reactivity in vitro and in vivo. The three-dimensional structure of cyclophilin from the yeast Malassezia sympodialis (Mala s 6) has been determined at 1.5 Å (1 Å=0.1 nm) by X-ray diffraction. Crystals belong to space group P41212 with unit cell dimensions of a=b=71.99 Å and c=106.18 Å. The structure was solved by molecular replacement using the structure of human cyclophilin A as the search model. The refined structure includes all 162 amino acids of Mala s 6, an active-site-bound Ala-Pro dipeptide and 173 water molecules, with a crystallographic R- and free R-factor of 14.3% and 14.9% respectively. The overall structure consists of an eight-stranded antiparallel β-barrel and two α-helices covering the top and bottom of the barrel, typical for cyclophilins. We identified conserved solvent-exposed residues in the fungal and human structures that are potentially involved in the IgE-mediated cross-reactivity.

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Peculiarities of the course of type I allergic reactions in patients with blood diseases

Terapevt (General Physician) ◽

10.33920/med-12-2004-06 ◽

2020 ◽

pp. 40-50

Author(s):

A. Nikitina

Keyword(s):

Search Engines ◽

Anaphylactic Shock ◽

Type I ◽

Allergic Reactions ◽

Common Cause ◽

Blood Diseases ◽

Treatment Regimens ◽

Modern Methods

Analysis of literature data presented in search engines — Elibrary, PubMed, Cochrane — concerning the risk of developing type I allergic reactions in patients with blood diseases is presented. It is shown that the most common cause of type I allergic reactions is drugs included in the treatment regimens of this category of patients. The article presents statistics on the increase in the number of drug allergies leading to cases of anaphylactic shock in patients with blood diseases. Modern methods for the diagnosis of type I allergic reactions in vivo and in vitro are considered.

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Previous Humoral Immunity to the Endemic Seasonal Alphacoronaviruses NL63 and 229E Is Associated with Worse Clinical Outcome in COVID-19 and Suggests Original Antigenic Sin

Life ◽

10.3390/life11040298 ◽

2021 ◽

Vol 11 (4) ◽

pp. 298

Author(s):

Daniele Focosi ◽

Angelo Genoni ◽

Ersilia Lucenteforte ◽

Silvia Tillati ◽

Antonio Tamborini ◽

...

Keyword(s):

Humoral Immunity ◽

Cross Reactivity ◽

Clinical Severity ◽

World Health ◽

Laboratory Findings ◽

Cellular And Humoral Immunity ◽

Rate Ratios ◽

Original Antigenic Sin

Antibody-dependent enhancement (ADE) of severe acute respiratory syndrome coronavirus-2 (SARS CoV-2) infection has been hypothesized. However, to date, there has been no in vitro or in vivo evidence supporting this. Cross-reactivity exists between SARS CoV-2 and other Coronaviridae for both cellular and humoral immunity. We show here that IgG against nucleocapsid protein of alphacoronavirus NL63 and 229E correlate with the World Health Organization’s (WHO) clinical severity score ≥ 5 (incidence rate ratios was 1.87 and 1.80, respectively, and 1.94 for the combination). These laboratory findings suggest possible ADE of SARS CoV-2 infection by previous alphacoronavirus immunity.

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Anti-CD63 antibodies suppress IgE-dependent allergic reactions in vitro and in vivo

Journal of Experimental Medicine ◽

10.1084/jem.20042085 ◽

2005 ◽

Vol 201 (3) ◽

pp. 385-396 ◽

Cited By ~ 47

Author(s):

Stefan Kraft ◽

Tony Fleming ◽

James M. Billingsley ◽

Shih-Yao Lin ◽

Marie-Hélène Jouvin ◽

...

Keyword(s):

Pi3k Pathway ◽

Therapeutic Agents ◽

Allergic Reactions ◽

Ecm Proteins ◽

Broad Array ◽

High Affinity Ige Receptor ◽

Nonadherent Cells ◽

Tetraspanin Cd63

High-affinity IgE receptor (FcεRI) cross-linking on mast cells (MCs) induces secretion of preformed allergy mediators (degranulation) and synthesis of lipid mediators and cytokines. Degranulation produces many symptoms of immediate-type allergic reactions and is modulated by adhesion to surfaces coated with specific extracellular matrix (ECM) proteins. The signals involved in this modulation are mostly unknown and their contribution to allergic reactions in vivo is unclear. Here we report the generation of monoclonal antibodies that potently suppress FcεRI-induced degranulation, but not leukotriene synthesis. We identified the antibody target as the tetraspanin CD63. Tetraspanins are membrane molecules that form multimolecular complexes with a broad array of molecules including ECM protein-binding β integrins. We found that anti-CD63 inhibits MC adhesion to fibronectin and vitronectin. Furthermore, anti-CD63 inhibits FcεRI-mediated degranulation in cells adherent to those ECM proteins but not in nonadherent cells. Thus the inhibition of degranulation by anti-CD63 correlates with its effect on adhesion. In support of a mechanistic linkage between the two types of inhibition, anti-CD63 had no effect on FcεRI-induced global tyrosine phosphorylation and calcium mobilization but impaired the Gab2–PI3K pathway that is known to be essential for both degranulation and adhesion. Finally, we showed that these antibodies inhibited FcεRI-mediated allergic reactions in vivo. These properties raise the possibility that anti-CD63 could be used as therapeutic agents in MC-dependent diseases.

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Allergenic Characterization of New Mutant Forms of Pru p 3 as New Immunotherapy Vaccines

Clinical and Developmental Immunology ◽

10.1155/2013/385615 ◽

2013 ◽

Vol 2013 ◽

pp. 1-12 ◽

Cited By ~ 6

Author(s):

C. Gómez-Casado ◽

M. Garrido-Arandia ◽

P. Gamboa ◽

N. Blanca-López ◽

G. Canto ◽

...

Keyword(s):

Food Allergy ◽

Ex Vivo ◽

Binding Capacity ◽

Cross Reactivity ◽

T Cell Epitopes ◽

Native Form ◽

Ige Binding ◽

Pru P 3

Nowadays, treatment of food allergy only considered the avoidance of the specific food. However, the possibility of cross-reactivity makes this practice not very effective. Immunotherapy may exhibit as a good alternative to food allergy treatment. The use of hypoallergenic molecules with reduced IgE binding capacity but with ability to stimulate the immune system is a promising tool which could be developed for immunotherapy. In this study, three mutants of Pru p 3, the principal allergen of peach, were produced based on the described mimotope and T cell epitopes, by changing the specific residues to alanine, named asPru p 3.01, Pru p 3.02, andPru p 3.03.Pru p 3.01showed very similar allergenic activity as the wild type byin vitroassays. However,Pru p 3.02andPru p 3.03presented reduced IgE binding with respect to the native form, byin vitro,ex vivo,and in vivo assays. In addition,Pru p 3.03had affected the IgG4 binding capacity and presented a random circular dichroism, which was reflected in the nonrecognition by specific antibodies anti-Pru p 3. Nevertheless, bothPru p 3.02andPru p 3.03maintained the binding to IgG1 and their ability to activate T lymphocytes. Thus,Pru p 3.02andPru p 3.03could be good candidates for potential immunotherapy in peach-allergic patients.

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Active immunization against the proregions of GDF9 or BMP15 alters ovulation rate and litter size in mice

Reproduction ◽

10.1530/rep-11-0336 ◽

2012 ◽

Vol 143 (2) ◽

pp. 195-201 ◽

Cited By ~ 20

Author(s):

C Joy McIntosh ◽

Steve Lawrence ◽

Peter Smith ◽

Jennifer L Juengel ◽

Kenneth P McNatty

Keyword(s):

Litter Size ◽

Transforming Growth Factor ◽

Transforming Growth Factor Β ◽

Cross Reactivity ◽

Full Length ◽

Ovulation Rate ◽

Corpora Lutea ◽

Immunization Group

The transforming growth factor β (TGFB) superfamily proteins bone morphogenetic protein 15 (BMP15) and growth differentiation factor 9 (GDF9), are essential for mammalian fertility. Recent in vitro evidence suggests that the proregions of mouse BMP15 and GDF9 interact with their mature proteins after secretion. In this study, we have actively immunized mice against these proregions to test the potential in vivo roles on fertility. Mice were immunized with either N- or C-terminus proregion peptides of BMP15 or GDF9, or a full-length GDF9 proregion protein, each conjugated to keyhole limpet hemocyanin (KLH). For each immunization group, ovaries were collected from ten mice for histology after immunization, while a further 20 mice were allowed to breed and litter sizes were counted. To link the ovulation and fertility data of these two experimental end points, mice were joined during the time period identified by histology as being the ovulatory period resulting in to the corpora lutea (CL) counted. Antibody titers in sera increased throughout the study period, with no cross-reactivity observed between BMP15 and GDF9 sera and antigens. Compared with KLH controls, mice immunized with the N-terminus BMP15 proregion peptide had ovaries with fewer CL (P<0.05) and produced smaller litters (P<0.05). In contrast, mice immunized with the full-length GDF9 proregion not only had more CL (P<0.01) but also had significantly smaller litter sizes (P<0.01). None of the treatments affected the number of antral follicles per ovary. These findings are consistent with the hypothesis that the proregions of BMP15 and GDF9, after secretion by the oocyte, have physiologically important roles in regulating ovulation rate and litter size in mice.

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The ER v-SNAREs are required for GPI-anchored protein sorting from other secretory proteins upon exit from the ER

The Journal of Cell Biology ◽

10.1083/jcb.200212101 ◽

2003 ◽

Vol 162 (3) ◽

pp. 403-412 ◽

Cited By ~ 47

Author(s):

Pierre Morsomme ◽

Cristina Prescianotto-Baschong ◽

Howard Riezman

Keyword(s):

Golgi Complex ◽

Protein Sorting ◽

Secretory Proteins ◽

Rab Gtpase ◽

Cargo Protein ◽

Conserved Oligomeric Golgi Complex ◽

Sorting Process ◽

Conserved Oligomeric Golgi

Glycosylphosphatidylinositol (GPI)-anchored proteins exit the ER in distinct vesicles from other secretory proteins, and this sorting event requires the Rab GTPase Ypt1p, tethering factors Uso1p, and the conserved oligomeric Golgi complex. Here we show that proper sorting depended on the vSNAREs, Bos1p, Bet1p, and Sec22p. However, the t-SNARE Sed5p was not required for protein sorting upon ER exit. Moreover, the sorting defect observed in vitro with bos1–1 extracts was also observed in vivo and was visualized by EM. Finally, transport and maturation of the GPI-anchored protein Gas1p was specifically affected in a bos1–1 mutant at semirestrictive temperature. Therefore, we propose that v-SNAREs are part of the cargo protein sorting machinery upon exit from the ER and that a correct sorting process is necessary for proper maturation of GPI-anchored proteins.

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Mesenchymal stem cells versus their extracellular vesicles in treatment of liver fibrosis: Is it possible to compare?

Medical Research Archives ◽

10.18103/mra.v9i2.2318 ◽

2021 ◽

Vol 9 (2) ◽

Author(s):

Noha Attia ◽

Yasmine Khalifa ◽

Dina Rostom ◽

Mohamed Mashal

Keyword(s):

Liver Fibrosis ◽

Extracellular Vesicles ◽

Therapeutic Strategy ◽

Secretory Proteins ◽

Apoptotic Bodies ◽

Limited Evidence ◽

In Vivo Models ◽

Dose Determination

Liver fibrosis (LF) is a worldwide health problem that is associated with a range of complications and high mortality. Due to the scarcity of liver donors, mesenchymal stem cell (MSC) therapy emerged as an alternative therapeutic strategy. However, it is widely accepted that most of the transplanted MSCs exhibit their therapeutic impact mainly via a bystander paracrine (medicinal) capacity. In addition to their secretory proteins, MSCs also produce various types of extracellular vesicles (EVs) that are classiﬁed into three main subtypes: microvesicles, exosomes and apoptotic bodies. Thanks to their peculiar cargo composition (e.g., proteins, lipids, and nucleic acids), EVs serve as an advantageous candidate for cell-free therapy. Recently, MSC-derived EVs (MSC-EVs) have gained the podium due to their regenerative and immunomodulatory effect. In mitigation/treatment of LF, a plethora of recent studies have shown the anti-inflammatory, anti-fibrotic and cytoprotective effects of both MSCs and MSC-EVs in various in vitro and in vivo models of LF. However, despite the limited evidence, we sought in this mini review to sort out the established data and formulate several challenging questions that must be answered to pave the way for further clinical applications. One of the major questions to ask is “Which is the best therapeutic approach, MSCs or MSC-EVs?” We tried to highlight how difficult it might be to compare the two approaches while our understanding of both candidates is still deficient. Among the major obstacles against such comparison is the inaccurate equivalent dose determination, the unknown in vivo behavior, and the undetermined lifespan/fate of each. Currently, the fields of MSCs and MSC-EVs seem to be rich in ideas but lacking in appropriate technologies to test these ideas. Nevertheless, continuous efforts are likely to help resolve some of the challenges listed here.

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MiR-154-5p-MCP1 Axis Regulates Allergic Inflammation by Mediating Cellular Interactions

Frontiers in Immunology ◽

10.3389/fimmu.2021.663726 ◽

2021 ◽

Vol 12 ◽

Author(s):

Misun Kim ◽

Hyein Jo ◽

Yoojung Kwon ◽

Myeong Seon Jeong ◽

Hyun Suk Jung ◽

...

Keyword(s):

Allergic Inflammation ◽

Passive Cutaneous Anaphylaxis ◽

Allergic Reactions ◽

Dependent Manner ◽

Cellular Interactions ◽

Array Analysis ◽

Molecular Features ◽

Rat Basophilic Leukemia Cells

In a previous study, we have demonstrated that p62, a selective receptor of autophagy, can regulate allergic inflammation. In the present study, microRNA array analysis showed that miR-154-5p was increased by antigen (DNP-HSA) in a p62-dependent manner in rat basophilic leukemia cells (RBL2H3). NF-kB directly increased the expression of miR-154-5p. miR-154-5p mediated in vivo allergic reactions, including passive cutaneous anaphylaxis and passive systemic anaphylaxis. Cytokine array analysis showed that antigen stimulation increased the expression of MCP1 in RBL2H3 cells in an miR-154-5p-dependent manner. Reactive oxygen species (ROS)-ERK-NF-kB signaling increased the expression of MCP1 in antigen-stimulated RBL2H3 cells. Recombinant MCP1 protein induced molecular features of allergic reactions both in vitro and in vivo. Anaphylaxis-promoted tumorigenic potential has been known to be accompanied by cellular interactions involving mast cells, and macrophages, and cancer cells. Our experiments employing culture medium, co-cultures, and recombinant MCP1 protein showed that miR-154 and MCP1 mediated these cellular interactions. MiR-154-5p and MCP1 were found to be present in exosomes of RBL2H3 cells. Exosomes from PSA-activated BALB/C mouse induced molecular features of passive cutaneous anaphylaxis in an miR-154-5p-dependent manner. Exosomes from antigen-stimulated RBL2H3 cells enhanced both tumorigenic and metastatic potentials of B16F1 melanoma cells in an miR-154-5p-dependent manner. Exosomes regulated both ROS level and ROS mediated cellular interactions during allergic inflammation. Our results indicate that the miR-154-5p-MCP1 axis might serve as a valuable target for the development of anti-allergy therapeutics.

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