What Class Of Antibodies Is Associated With The Peanut Allergy

Infobox 2 Food Allergen Families

Cupin superfamily: Ara h 1 and 3

Prolamin superfamily: Ara h 2, 6, 7 and 9

Profilin: Ara h 5

PR-10 protein: Ara h 8

Oleosin: Ara h 10, 11, 14 and 15

Defensin: Ara h 12 and 13

Allergens in a food are considered major allergens if they are recognized by 50% of the allergic population via the specific serum- IgE antibodies. The major allergens in peanuts are Ara h 1 and Ara h 3 and Ara h 2 and Ara h 6 . Minor allergens are recognized in less than 50% of the allergic population. Minor allergens in peanuts include, for example, Ara h 5 from the profilin protein family and Ara h 8 from the Bet v 1 family .

A Potential Life Changer

Experts see some far-reaching changes to peoples lives with a treatment like the one used in the study.

A vaccine that could limit or end allergic reactions to peanuts would be life changing for patients, Kathleen Dass, MD, an allergist and immunologist in Oak Park, Michigan, told Healthline.

A very promising feature of this is that, unlike with desensitization, patients do not have to have exposure to peanut until it is safe to do so she said. If this vaccine was approved for patients, it would be a life saving treatment option that I would implement as soon as I could.

Punita Ponda, MD, assistant chief of the department of allergy and immunology at Northwell Health in Great Neck, New York, said the findings of the new study are exciting.

In the past, we just told people to avoid certain foods, she told Healthline.

Ponda noted the small size of the study and the need for more research, but she added the placebo-controlled Stanford study was well designed with all participants confirmed to have food allergies through oral challenges.

Inhibition Of Basophil Activation By Post

The same receptor-mediated inhibition of IgE-induced activation by IgG has also now been clearly demonstrated in patients undergoing OIT. Using an indirect basophil activation test , Burton and colleagues analyzed suppressive activity in the serum of peanut-allergic patients who underwent OIT . In the iBAT, basophils from a non-allergic donor are used to interrogate the sera of study subjects for both activating and suppressive factors . IgE-containing serum, typically from a peanut allergic patient, is added to these basophils in culture. After the addition of peanut extract, granule extrusion is measured by flow cytometric quantitation of CD63, a granule protein that is similar to the LAMP-1 marker used in the murine system. Using this assay, the group found decreased basophil activation by iBAT following completion of OIT. When both pre- and post-OIT serum from the same individual were incubated with donor basophils, the degranulation was lower than that induced by pre-OIT sera alone, indicating that the suppressive activity was OIT-induced . It was determined that this suppression is IgG-mediated and could be blocked by antibodies to FcRIIb.

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Ige And Mast Cell Homeostasis

In addition to enhancing FcRI levels on the surface of mast cells, IgE antibodies promote mast cell survival and proliferation in vitro and in vivo. The derivation and propagation of mast cells from bone marrow stem cells require the presence of IL-3 and SCF. Without these cytokines, BMMCs undergo apoptotic cell death. However, the addition of IgE both enhances the proliferation of BMMCs in the presence of IL-3 and SCF, and protects them from apoptosis upon withdrawal of IL-3, suggesting an important role for IgE in mast cell expansion in settings of type 2 inflammation, and for survival in growth factor limiting conditions . Such a function of promoting mast cell expansion and survival has in fact been observed in mouse models of parasitic worm infections. IgE promotes splenic mast cell expansion and parasite clearance in the course of Trichinella spiralis infection . Similarly, in an asthma model, sensitization of mice by inhalation of the fungus Aspergillus fumigatus drives mast cell expansion in the bronchus, trachea, and spleen and this expansion is dependent on the presence of IgE antibodies . Together, these findings reveal that IgE antibodies not only act to trigger mast cell degranulation and regulate FcRI levels, but also promote mast cell survival and expansion.

Antibodies: The Bodys Red Flag

Before explaining the differences, letâs discuss exactly what IgG and IgE areâprotective antibodies.

When the body judges a foreign substance as dangerous, the immune system fights back just as if it was fighting an illness.

The bodyâs weapon of choice? A class of antibodies known as immunoglobulins.

Depending on the severity of the reaction, different immunoglobulins are used. The bodyâs three food-related immunoglobulins include :

• Immunoglobulin E â A rapid immune response that can be triggered by food
• Immunoglobulin G â A more delayed and potentially more mild immune response that can be triggered by food
• Immunoglobulin A â An antibody that can support the immune functions of mucous membranes

IgE and IgG tests could be the key to unlocking additional food-related insights.

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Therapeutic Applications Of Igg

A significant limitation of the IgG antibody approach is that any given allergen-specific IgG therapeutic would only target a single allergen. It is unclear if IgG specific for each component allergen would be required for effective therapy. Since the inhibitory signal delivered to the mast cell by IgG against any protein within a food, it is possible that targeting just one component would be sufficient. A variety of alternative approaches have been explored using bispecific antibodies or fusion proteins that bring bridge FcRI and FcRIIb . Several groups have reported the development of bifunctional FcRI crosslinkers composed of the Fc portion of IgG1 and the Fc portion of IgE or an allergen . However, molecules containing the Fc portion of IgE might be limited in their activity by the availably of free FcRI sites. Tam et al. designed a bispecific antibody consisting of a Fab fragment that recognizes human IgE and a Fab fragment that recognizes FcRIIb. Incubation of IgE-sensitized cord blood derived mast cells and basophils with the bispecific antibody blocked histamine release following antigen challenge . Similarly, Jackman and colleagues described a bispecific antibody in which one arm recognizes FcRI at a site not blocked by IgE binding, while the other arm binds to FcRIIb .

Cd2: The Low Affinity Receptor For Ige

IgE can also bind to and exert its effects through its low affinity receptor CD23 . CD23 is broadly distributed with expression on B cells, dendritic cells, eosinophils, gastrointestinal and respiratory epithelial cells, and others . It is a type II transmembrane protein assembled as a multimer with -helical coiled-coil stalks terminating in C-type lectin heads that bind to IgE . CD23 is the only Fc receptor that is not part of the immunoglobulin superfamily. In addition to binding IgE, it also interacts with the B cell surface protein, CD21, which functions as complement receptor 2 and is the binding site and entry point for Epstein-Barr virus in B cells . Protease-sensitive sites present in the stalks of CD23 can be cleaved by endogenous proteases such as the metalloproteinase, ADAM10, and by protease allergens including the dust mite protease, Der p 1. The released oligomeric CD23 heads are called soluble CD23 and retain their ability to bind IgE.

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Fcriib: The Inhibitory Igg Receptor

FcRIIb is the only inhibitory IgG receptor and one of its main function is to turn off signals initiated by activating Fc receptors and the B cell receptor . The importance of IgG-mediated feedback control of humoral immunity by FcRIIb has long been appreciated . Co-aggregation of FcRIIb with the BCR increases the BCR activation threshold and suppresses B cell-mediated antigen presentation. In the absence of FcRIIb, the amount of antigen needed to activate B cells is increased, and production of antibodies to T cell-dependent antigens is suppressed . FcRIIb signals can inhibit the maturation of dendritic cells as well as their FcR-mediated antigen presentation and T cell priming . In macrophages, FcRIIb inhibits FcR-mediated phagocytosis and release of cytokines . Overall, FcRIIb is the most widely expressed FcR and its presence on various cell types is required for maintenance of peripheral tolerance.

Medical History As Well As Nutritional And Symptom Protocol

A central building block in suspected peanut allergy is a careful allergologic history.

The history includes, but is not limited to:

• The patients own medical history,

• The specific nutritional history, and

• Family history.

The reported symptoms should be recorded with their local, temporal and situational occurrence. For this the last 23h before the allergic reaction in relation to food consumption and augmentation factors are crucial. In the case of multiple reactions, the individual reactions should be described in detail and, if possible, independently of each other. Potentially occurring augmentation factors should also be considered, as these may influence the reaction severity and threshold .

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Basophil Activation And Inhibition Assays

Basophil activation following pre- and post-immunotherapy plasma transfer. Assay schematic in which peanut allergic plasma is replaced with either 0 month or 12 month OIT plasma then stimulated with peanut extract . Representative %CD63+ basophil results are shown . Basophil activation for cells incubated with plasma from subjects on 0 or 12 months OIT, 0 or 12 months of placebo or 12 months of placebo followed by 12 months of OIT . PN-sIgE and PN-sIgG4 shown for subjects on 0 months or 12 months of OIT or placebo. Individual data are shown in C and F red lines indicate medians *p< 0.05, **p< 0.01, ****p< 0.0001.

Inhibition capacity of IgG-depleted plasma or the IgG fraction isolated from plasma. Percent CD63+ basophils following incubation with undiluted, sham-depleted, or IgG-depleted 0 month or 12 month OIT plasma and stimulation with peanut extract . Percent CD63+ basophils following incubation with undiluted, IgG-depleted or IgG fractions from 18 month OIT plasma and stimulation with peanut extract . Individual data are shown red lines indicate medians *p< 0.05, **p< 0.01.

Oral Food Challenge Testing

The gold standard of a diagnosis of primary peanut allergy is a standardized, double-blind, placebo-controlled oral food challenge . Oral titrated peanut food challenges can also be performed openly. However, this option should only be considered if there is a very high probability of a negative result. Especially with increasing age and increased anxiety about the expected reaction, when assessing a late reaction , or following an unclear open food challenge, double-blind placebo-controlled food challenge should be performed .

Although false-positive placebo reactions are rare , one study showed that this affected younger children more often , as opposed to older children . This again emphasizes the importance of DBPCFC testing also in infancy and toddlerhood.

Table 4 Quantities of a titrated oral food provocation to peanut. Modified after

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Antibody Injection Stops Peanut Allergy For 2 To 6 Weeks Study Shows

A Stanford-led pilot study has provided early evidence that an antibody is a safe, effective and rapid food allergy treatment.

Kari Nadeau

One injection of an antibody treatment let people with severe peanut allergies eat a nuts worth of peanut protein two weeks later, a small, Stanford-led pilot study showed.

The study provides early evidence that the antibody is a safe, effective and rapid food allergy treatment. A paper describing the findings was published online Nov. 14 in JCI Insight.

Such a treatment is badly needed. About 32 million Americans suffer from food allergies, which can develop at any point in life. The only existing treatment, oral immunotherapy, requires patients to eat tiny, gradually escalating doses of their food-allergy triggers under medical supervision. Desensitizing someone to their allergens with oral immunotherapy takes six months to a year, and can cause allergic reactions along the way.

In contrast, 73% of the people who received the antibody, all of whom had severe peanut allergies, could eat a modest amount of peanut protein 15 days after a single injection of the treatment.

The studys lead author is Sharon Chinthrajah, MD, clinical associate professor of medicine and of pediatrics. Nadeau and Chinthrajah treat allergy, asthma and immunology patients through Stanford Health Care and Stanford Childrens Health.

Infobox 1 Potential Augmentation Factors

• Physical activity

• Medication intake

• Sleep deprivation

• Alcohol consumption

In addition, the past and current history of other diseases of the atopic spectrum should be inquired about, such as atopic dermatitis, allergic rhinoconjunctivitis, allergic bronchial asthma, and other food allergies. Especially children with atopic dermatitis and/or chicken egg allergy seem to be predisposed to peanut allergy . If peanut allergy is suspected in infants and young children, the childs past diet, including any history of peanut consumption, should be inquired about. It should be emphasized that peanut allergy may be present in the infant without previous reactions or peanut intake being known to the parents. If, on the other hand, peanuts have already been eaten regularly and are well tolerated, a primary peanut allergy can be largely excluded.

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An Alternative To Desensitization

Experts said the research demonstrates the potential for an alternative or adjunct to desensitization treatment, which is currently the only proven way to combat food allergies.

Desensitization involves giving people with allergies small amounts of their trigger foods, with amounts slowly increasing over a 6-month to 12-month course of treatment.

The lengthy treatment process must be done under medical supervision and allergic reactions can occur.

Whats great about this treatment as an option for food allergies is that people did not have to eat the food to get desensitized, Nadeau told Healthline.

Although this is still in the experimental stages, were delivering on the hope of testing a drug that wont be for one food allergy but for many, and for other allergic diseases, too.

Nadeau and R. Sharon Chinthrajah, MD, a lead study author, treat allergy, asthma, and immunology patients at Stanford.

Food allergies, which can develop at any point in life, affect an estimated 32 million people in the United States.

After cows milk and eggs, peanut allergies are the third most common food allergy . Peanut allergies affect about 1 in 50 children and 1 in 200 adults.

Theyre also the most common food allergen to cause a fatal anaphylactic reaction.

Downregulation Of Ige Receptor By Omalizumab

Omalizumab is a recombinant humanized IgG antibody that recognizes the Fc portion of IgE. Its affinity for free IgE is greater than that of IgE for its receptor so it can effectively compete for free IgE and prevent its binding to cell surface FcRI. However, omalizumab cannot effectively disrupt established interactions between IgE and FcRI. Once free IgE is captured by omalizumab, immune complexes are formed that are eventually cleared from circulation. By reducing the ambient free IgE concentration, omalizumab leads to a downregulation of FcRI. Allergic patients that have been treated with omalizumab have low density of FcRI on the surface of basophils, mast cells, and dendritic cells . Thus, more than the removal of circulating allergen-specific IgE, this secondary effect of omalizumab on FcRI density is critical in its mechanism of action in the treatment of hypersensitivity reactions.

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Restoration Of Tolerance During Adjunctive Therapy With Igg During Oit

OIT can also be modeled in OVA-sensitized Il4raF709 mice. Mouse models of food allergy using this line have been applied to test the hypothesis that allergen-specific IgG given during the course of OIT might enhance the effectiveness of OIT, by dampening Th2-inducing signals. As expected, OIT, even without adjunctive IgG, resulted in diminished allergen sensitivity, as assessed by anaphylaxis and MMCP-1 release. However, the protective effects of IgG were dramatically amplified in mice receiving OVA-specific IgG during their OIT with complete abrogation of anaphylaxis and markedly blunted Th2 and IgE responses .

What Are The 5 Types Of Antibodies

Your immune system produces five types of antibodies, each of which has distinct methods of defending your body against disease and infection.

Antibodies are specialized Y-shaped proteins made by the immune system. They help fight disease by detecting viruses, bacteria, and other pathogens and working to destroy them. Harmful infectious organisms are identified as invaders due to their antigens, which are distinct molecules on their surface. Each antibody produced by your immune system binds to a specific antigenwith a fitted molecular shapeand then either destroys the pathogen or tags it so other immune cells will recognize it.

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Igg Antibody Depletion And Enrichment

Pierce Protein A/G Agarose Beads were washed 3 times with PBS prior to use. According to the manufacturer, these beads have high affinity to all human IgG subclasses, and a weaker interaction with IgA, IgE and IgM. An equal volume of beads and plasma, or PBS and plasma were mixed and incubated on a rotator for 90 minutes for IgG depletion or sham depletion, respectively. Plasma was separated from the beads by centrifuging at 1,000 Ã g for 90 seconds and the supernatant collected. IgG fractions were eluted from the beads with 0.1 M glycine , and neutralized with 1 M Tris . The presence of IgG was assessed with a Total Human IgG ELISA kit . Peanut-specific IgE, IgG4, and IgG values from the sham and IgG-depleted samples were quantified using a Phadia ImmunoCAP100 according to manufacturerâs instructions.

Memory B Cells Maintain Lifelong Food Allergies

One recent publication proposed that mice chronically exposed to house dust mite generate long-lived IgE-secreting cells which home to the bone marrow and maintain titers of allergen-specific IgE.15 In the same study, IgE+ PCs were detected in the bone marrow of cat allergic patients, but the longevity of these cells is not known. In patients avoiding food allergens, exposures are thought to be rare and therefore do not likely provide the chronic stimulus required for these observations. Additional research is required to understand the importance of this axis in food allergy.

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Igg Antibodies In Allergic Diarrhea

IgE-mediated gastrointestinal reactions, including diarrhea, are common in IgE-mediated food allergy. The effects of food allergen-specific IgG antibodies in both anaphylaxis and diarrhea were investigated by Kucuk and colleagues in a hybrid model of food allergy involving both active sensitization and passive transfer of IgG . Though anaphylaxis and diarrhea are both IgE- and FcRI-mediated, the mast cell mediators driving these phenotypes appear to be different. Histamine is associated with anaphylactic shock, while platelet activating factor and serotonin are associated with diarrhea . To address whether IgG can confer protection against the diarrhea phenotype, Kucuk et al. tested if anti-TNP IgG1 administration prevents the diarrhea induced by TNP-BSA challenge in sensitized mice. When the investigators tested the phenotypes on the FcRIIb-/- background, protection against anaphylaxis by IgG1 antibodies was no longer observed while IgG1-mediated inhibition of diarrhea was, surprisingly, retained . These findings suggest that while IgG-mediated inhibition of shock is dependent on signaling via FcRIIb as has been confirmed by others, that inhibition of diarrhea may be due to steric hinderance of antigen-IgE binding rather than a receptor-mediated mechanism .