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Alergia alimentaria mediada

por IgE
Paralelo 02 - Grupo 9
Karla Tarira, Daniela Santamaría, Valeria Enríquez
Epidemiología
In Europe and the US, between 6% and 8% of children suffer from
food allergies.

Gold standard: double-blind placebo-controlled food challenge


(DBPCFC) - specialized centers.
● > Reportes de padres.
Fuente: Immunoglobulin E (IgE)-Mediated Food Allergy in Children.
Prevalence of:
● Fish allergies: 0% to 7%
● Shellfish allergies: 0% to
10.3%

Prevalence of tree nut


allergies: less than 2%
● Europe: > hazelnut
● US: walnut and
cashew

Fuente: Allergy, Asthma & Sinus Center, P.C.


Epidemiología

● 9336 children followed up until 2 years of age.


● Cow’s milk allergy
○ Netherlands: 0.54%
○ UK: 1%
○ Lithuania, Germany and Greece: < 0.3%
● Hen’s egg allergies: 1.23%

Fuente: Immunoglobulin E (IgE)-Mediated Food Allergy in Children.


Epidemiología

First study to accurately describe the natural history of food allergy


and other allergic diseases throughout childhood to adolescence.

● 5276 one-year-old children from Australia.


1. Prevalence of 11% of food allergies (oral food challenge):
○ Peanuts (3%)
○ Raw eggs (8.9%)
○ Sesame (0.8%)
2. Follow-up at 4 years old: 3.8%
○ Peanuts (1.9%)
○ Raw eggs (1.2%)
○ Sesame (0.4%)

Fuente: Immunoglobulin E (IgE)-Mediated Food Allergy in Children.


Fisiopatología
Regular passage of food antigens:

- 2 transport systems:

Passive: Paracellular diffusion

Active: through microfold (M) cells,


globlet cells (CX3CR1), CD103+
dendritic cells.

|
Induce regulatory T cells (Treg) through
IL-10 (macrophages) or TFG-B (dendritic
cells).

Fuente: Food allergy: immune mechanisms, diagnosis and immunotherapy (2016)


Fisiopatología

The lack of immunologic and clinical


tolerance to food allergens leads to food
allergies.

The tolerance to food antigens breaks down


in exposure to PAMPs or following
epithelial damage.

Production of IL-25, IL-33 and TSLP induce


Treg cells switch to antigen specific Th2
cells, which produce IL-4.

IL-4 causes the production of IgE and


stimulate mast cell expansion.

ILC2s produce IL-4 and IL-13.

Fuente: Food allergy: immune mechanisms, diagnosis and immunotherapy (2016)


Finally…
IgEs bind the receptors present on the
surface of mast cells.

In exposure to the same food antigens:

- Degranulation of those cells that


release mediators
- Histamine
- Leukotrienes
- Cytokines
- Protaglandins

Fuente: Immunoglobulin E (IgE)-Mediated Food Allergy in Children.


Clinical manifestations

IgE-MEDIATED REACTIONS

1. Urticaria and angioedema


2. Oropharyngeal symptoms
3. Respiratory tract symptoms
4. Gastrointestinal symptoms
5. Anaphylaxis

Fuente: UpToDate
Diagnóstico

MEDICAL HISTORY

SKIN PRICK TEST


in-vivo - in-vitro

ELIMINATION DIET

ORAL FOOD
CHALLENGE

Fuente: Immunoglobulin E (IgE)-Mediated Food Allergy in Children.


Undetectable
values of s-IgE
are associated to
a low risk
(10–25%) of
reaction to the
food.
Diagnóstico
Basophil Activation Test (BAT) --- in-vitro OFC.

Flow cytometry.

Sensitivity ranges from 77% to 98%, and specificity from 75% to 100%.

https://www.jove.com/es/v/62600/basophil-activation-test-for-allergy-diagnosis
Management

● Many believe that the only strategy currently available


for the treatment of food allergies is the strict
elimination diet.

● Patients with food allergies, at risk of serious


reactions, should always carry a drug kit with an
adrenaline autoinjector for immediate self-treatment.

● There are different types of immunotherapy, based on


the administration route, and namely, oral
immunotherapy (OIT) where the allergen is swallowed,
sublingual immunotherapy (SLIT) where the allergen is
held under the tongue for 2 min and then split or
swallowed, and epicutaneous immunotherapy (EPIT),
where a patch with a food allergen is applied on the
skin
Management

The typical protocol of


oral immunotherapy
includes an initial
escalation phase

The aim of
immunotherapy is to
reach “a state of
tolerance” in which the
patient does not show
any reaction after
ingestion of a normal
serving of the culprit
food despite a period of
absence of
exposure.
Allergen immunotherapy

The most advanced therapeutic approach is


based on controlled allergen exposure (allergen
immunotherapy), given by different routes:
Microbial therapeutics -Oral immunotherapy (OIT)
-Epicutaneous immunotherapy (EPIT)
-Based on studies showing that ex vivo -Sublingual immunotherapy (SLIT)
transfer of stool from food-allergic
patients and healthy patients could Food allergen immunotherapy is associated
confer susceptibility and protection with a reduction in allergen-specific Th2 cells,
from food allergy in mouse models. including reduced Th2A cells.

-Other microbial therapies are being


combined with oral immunotherapy to
promote a tolerogenic mucosal immune IgE targeting
environment while providing allergen.
Targeting of Th2 pathways is
hypothesized to be effective by having
an end effect on allergen-specific IgE.
Biologies targeting Th2 pathways A benefit of targeting IgE is the
antigen non-specificity of the
approach. Reduction in IgE on the
Cytokines that drive Th2 pathways surface of cells should reduce allergic
including TSLP, IL-33, and IL-25 are reactions to any food
secreted by epithelial cells of the skin or
gastrointestinal tract, and neutralization
inhibits food allergy in mice
Suppressing effector cells

Food-allergic reactions are mediated by IgE signaling through the


high-affinity FcεRI receptor on mast cells and basophils. A
cascade of kinases, including Lyn, Syk, and Bruton’s tyrosine
kinase (BTK), regulate calcium signaling and control cell
degranulation.

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