Lecture 22 - Food Allergy Flashcards

1
Q

Characterise the prevalence of immune disorders

A
Since 1950:
 • Exponential increase in immune disorders
- MS
- Type I diabetes
- Asthma
- Crohn's disease
- Food allergy & anaphylaxis

The increase is seen across all age groups, but children 0-4 in particular

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2
Q

What is anaphylaxis?

A

Most severe form of allergic reaction
Rapid onset
May cause death

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3
Q

What are the determinants of allergic disease?

A
  1. Genes
  2. Early life environment:
    • Microbial exposure (most important)
    • Vit D
    • UV light
    • Diet
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4
Q

Describe the effect of genetics and environment leading to disease

A
  1. Genes & environment
  2. Epigenetic modification
  3. Gene expression
  4. Altered immune tolerance
  5. Disease
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5
Q

Describe the observations from studies of mice in germ free conditions

A

“Fail to develop oral tolerance”:
• Underdeveloped Peyer’s patches lacking GCs
• Few IgA plasma cells and CD4+ T cells in LP
• Reduced n° of IELs
• Fail to develop oral tolerance
• Persistent Th2 responses

Window of opportunity:
• These abnormalities can be reversed, but only in the neonatal period

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6
Q

Compare intestinal microbiota in allergic and non-allergic children

A

Allergic:
In general:
• Decreased levels of probiotic bacteria
• Increased levels of pathogenic bacteria

  • ‘Good’ Bifidobacterium levels reduced and less adherent to intestinal mucous
  • Microbiota induce less IL-10 production
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7
Q

Which bacteria are probiotic?

Which bacteria are pathogenic?

A

Probiotic:
• Lactobacillus
• Bifidobacteria

Pathogenic:
• C. difficile
• S. aureus

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8
Q

When is abnormal microbiota seen in children?

A

Preceding the development of allergic disease

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9
Q

Describe the changes to microbiota over the first 12 months of life in children who will develop allergic disease

A

1 month:
• decreased bifidobacteria
• decreased colonisation of Enterococci
• increased Clostridia

6 months:
• increased Staphylococcus

12 months:
• decreased Bacteroides

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10
Q

Why is microflora important for disease?

A

Intestinal microflora plays a vital role in:
• Immune system maturation
• Development of tolerance

Which are required to avert allergic responses

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11
Q

What is the prevalence of food allergy?

A

2% - 5% of population

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12
Q

Which group of people most common experience food allergy?

A

Children: 6-10%

Compared to
Adults: 2%

Food allergies resolve with age

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13
Q

What are the major food groups that cause allergy?

A
In order of increasing prevalence:
 • Peanuts
 • Tree nuts & seeds
 • Fish
 • Crustaceans
 • Eggs
 • Milk products
 • Fruit & veg
 • Food additives
 • Wheat

8 major food groups cause > 90% of food allergy

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14
Q

What are the common food allergies in children?

Compare this with adults

A

Children:
• Egg, milk, peanut
• Soy, wheat, fish

Adults:
• Peanut, tree nuts, fish, shellfish

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15
Q

What are the various clinical symptoms caused by the IgE mediated allergic reaction?

A
  • Urticaria

* Angioedema

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16
Q

What is urticaria?

A

Hives:
• IgE mediated allergic reaction
• Red bumps on skin
• Similar to angioedema, but only occurs in the upper dermis

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17
Q

What is angioedema?

A

Rapid swelling of dermis, subcutaneous tissue, mucosa & submucosa

Around eye

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18
Q

What are the symptoms in the following regions due to the IgE mediated allergic reaction?
• Airway
• Cardiovascular system

A
1. Airway
 • Hoarse voice
 • Difficultly swallowing & breathing
 • Feeling of tightness in throat
 • Coughing
 • Wheeze
  1. Cardiovascular
    • Drowsy
    • Collapse
    • Pale and floppy
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19
Q

How is food allergy managed?

A

• Allergen avoidance

• Education:
- management of allergic reactions - preparation for anaphylaxis

• Adrenaline auto-injector

20
Q

Is allergen avoidance successful?

A

No, it’s difficult

  • 50% of children have accidental ingestion within 1 yr
  • In fatal cases most were aware of the allergy but failed to avoid the food
  • 40-100% of fatal reactions were from food prepared outside the home
21
Q

Is the EpiPen widely used?

A
  • 75% carried it
  • 10% were expired
  • 32% could use it correctly

Requires regular training

  • Even when used, person can die:
  • In 12-14% of fatal cases there were early, repeated doses of adrenaline
22
Q

Describe the mechanism for loss of tolerance to food

A
  • Increased Th2, decreased Th1
  • Reduced Treg numbers & activity
  1. Allergen in gut
  2. Allergen taken up by DCs
  3. Allergen presentation to Th2
  4. Stimulation of B-cells to produce IgE
    → Food allergy
23
Q

What was observed in the immune response in resolution of food allergy?

A
  • Shift to Th1 responses

* Increased allergen specific Tregs

24
Q

Compare Desensitisation & tolerance

How are they measured?

A

Desensitisation: the ability to tolerate a food while ingesting regular doses of the food
• Rapidly reversible
• Mediated by changes in effector cells (mast cells, basophils)

Tolerance: Ability to tolerate a food after a period of time has elapsed since ingesting the food
Expected to last for months-years after stopping therapy

Measured by:
Desensitisation: oral food challenge whilst still on treatment
Tolerance: oral food challenge after stopping therapy

25
What immunological changes occur in tolerance?
• Induction of allergen-specific Tregs Less common: • Allergen specific anergy / clonal deletion
26
Describe the mechanism of immunotherapy
1. Injected allergen taken up by APC 2. Presented to Treg 3. Treg produces suppressive cytokines (IL-10, TGF-beta) 4. Suppression of Th2, stimulation of Th1 → Reduced IgE → Incresed IgA & IgG4
27
What was seen in immunotherapy for peanut allergy?
* Desensitisation: threshold for allergen increased from 178mg to 2805mg * High rate (39%) of serious systemic reactions
28
Describe efficacy of oral immunotherapy What are the immunological changes? What are the drawbacks?
• Majority of patients successfully desensitised - i.e., whilst still receiving OIT they were tolerant of cow's milk • Yet to achieve tolerance Immunological changes: • Decreased milk IgE • Increased milk IgA & IgG4 • Increased IFN-gamma Draw backs: • Limited ability to induce tolerance • Allergic reactions during treatment are common • Severe reactions (10-20%)
29
Describe the study of high dose Egg OIT
Aiming to induce tolerance * Placebo group: 0% tolerance * Treatment group: 28% tolerance
30
What was observed in long term follow up of OIT?
* Milk OIT for 4.5 years * Well tolerated (desensitised) * Regular ingestion of milk * No evidence of tolerance * Recurrence of allergy in subjects who discontinued OIT for period of a few weeks
31
How could OIT be improved?
* Higher maintenance dose | * Adjuvant
32
Describe the use of adjuvants in OIT Give examples
Immune response modifiers: • Target TLRs with ligands linked to allergens • Aims to resolve Th1 / Th2 imbalance Examples: 1. CpG-containing-DNA-allergen complexes • Increased in allergen-specific Th1 responses ``` 2. Monophosphoryl lipid A • Bacterial cell wall component • Binds TLR4 • Decreased IgE • Increased IgG4 ```
33
What is the PPOIT study?
Probiotic and Peanut OIT study • Two groups: 1. Probiotic (LGG) + Peanut OIT 2. Placebo * Many samples taken at various points in time * Oral food challenge at end of treatment course Preliminary results: • Skin prick tests: • Desensitisation observed in treatment group
34
What is the most important environmental feature in regards to allergy?
Microbial exposure during fist few weeks and months of life
35
Is dysbiosis reversible?
Yes, but only in the neonatal period
36
How can microflora be targeted to help allergic disease?
Probiotics & diet to resolve dysbiosis
37
What is observed in terms of IL-10 in the MALT of people with allergic disease?
Microbiota of individuals with allergic disease induce less IL-10 production
38
Why are adults less commonly affected by food allergy?
Allergies can resolve over time
39
Which food allergies tend to resolve with age? | Which do not?
Resolve with age: • Cow's milk • Egg • Wheat Do not resolve with age: • Peanut • Shellfish
40
What is the time frame for IgE mediated allergic reaction?
30 mins - 1 hr
41
Describe multi-system involvement in the IgE mediated allergic reaction
Skin: • Urticaria • Angioedema • Eczema Gastrointestinal: • Vomiting • Diarrhoea • Cramps Respiratory: • Coughing • Wheezing Cardiovascular: • Hypotension
42
What is the first clinical sign of the IgE mediated immune response?
Urticaria
43
What is the biggest treatment strategy for allergy?
Management: • Allergen avoidance • Having an action plan for anaphylaxis EpiPen
44
Which cytokines released by Th2 are involved in skewing towards B cell IgE production?
IL-4 IL-5 IL-13
45
What are the two types of immunotherapy?
Earlier: Subcutaneous immunotherapy Now: Oral immunotherapy (OIT)
46
What were the results of the RCT of OIT for peanut allergy?
(RCT: randomised controlled trial) | No effect observed, i.e. same rates of tolerance observed in both the 'OIT' and 'avoid' groups
47
What were the results of the high dose OIT for egg allergy?
Considerable result: 28% tolerance in OIT group 0% tolerance in control group