Allergy Update - abacusdx.com · • Precipitins to A. fumigatus or sIgG to A. fumigatus OR changes...
Transcript of Allergy Update - abacusdx.com · • Precipitins to A. fumigatus or sIgG to A. fumigatus OR changes...
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Allergy Update
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ImmunoCAP sIgG
measurement
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ImmunoCAP Specific IgG
Measures antigen-specific IgG antibodies in human
serum and plasma.
Part of the natural defence system of the body and
develop in response to contact with foreign substances.
Marker of exposure to that antigen.
Level of specific IgG in serum usually reflects the extent
of exposure to that antigen.
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Expected test values
No common cut-off value for specific IgG antibodies
Markers for antigen exposure and are not directly related to the disease.
Results vary both within and between antigens.
Geographical variations are also important, as are individual levels of exposure.
To determine if levels are increased, the reference level of specific IgG antibodies to a certain antigen should be measured in a number of samples from normal healthy persons and, if possible, compared with the levels in a group of patients.
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Valuable Clinical Information
Allergic disease
• In clinical studies with asthma, rhinitis, urticaria, eczema
and gastrointestinal disorders
• As a marker for exposure in different lung diseases, e.g.
allergic alveolitis, aspergilloma and aspergillosis
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Background: Exposure to organic dust produced by
birds often gives rise to an immune response, e.g. IgG
antibodies, but intense exposure can lead to high
concentrations of IgG antibodies and the development of
allergic alveolitis, often known as ‘bird fancier’s lung’.
Conclusion: Threshold values […] were 9.8, 10.8 and 10.0
mg/l for pigeons, budgerigars and parrots, respectively.
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Pulmonary Aspergilloma
Mass caused by a fungal infection that usually grows in
lung cavities.
Formed when the fungus Aspergillus grows in a clump in a
lung cavity, or invades healthy tissue, causing an abscess.
The most common species of fungus that causes disease
in humans is Aspergillus fumigatus.
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Symptoms & Exams
When symptoms do
develop, they can include:
• Chest pain
• Cough
• Coughing up blood
• Fatigue
• Fever
• Unintentional weight loss
Tests:
• Biopsy of lung tissue
• Blood test for presence of aspergillus in the body (galactomannan)
• Bronchoscopy or bronchoscopy with lavage
• Chest CT
• Chest x-ray
• Sputum culture
• Blood test to detect antibodies to aspergillus(serum precipitins for aspergillus) = sIgG Ab
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Allergic Bronchopulmonary aspergillosis
in cystic fibrosis patients
10% of patients with cystic fibrosis
For the diagnosis:
• Clinical deterioration
• Elevated Total IgE (>500IU/ml)
• Raised Ige to A. fumigatus
• Precipitins to A. fumigatus or sIgG to A. fumigatus OR
changes on chest X-ray not clearing with antibiotics and
physiotherapy
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Prospective cohort study of 175 adult patients with chronic or allergic pulmonary aspergillosis.
Aspergillus IgG antibodies detected using CIE, PhadiaImmunoCap Aspergillus IgG and Bio-Rad PlateliaAspergillus IgG.
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Results:
• When compared with CIE, both ImmunoCap and Platelia Aspergillus IgG had good sensitivity (97 and 93%, respectively).
• The level of agreement between the two EIAs for positive results was good, but the concentration of antibodies was not correlated between the tests or with CIE
• titre.
• ImmunoCap IgG inter-assay coefficient of variation was 5%, whereas PlateliaIgG was 33%.
• Median ImmunoCap IgG values for CPA and allergic aspergillosis were 95 and 32 mg/L, respectively, whereas Platelia IgG values were >80 and 6 AU/mL.
• The direction of CIE titre change over 6 months was mirrored by ImmunoCapIgG levels in 92% of patients, and by Platelia IgG in 72% of patients.
Conclusion:
Both ImmunoCap and Platelia Aspergillus IgG EIAs are sensitive measures of Aspergillus IgG antibodies compared with CIE. However, ImmunoCap appears to
have better reproducibility and may be more suitable for monitoring patient disease.
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Determination of Aspergillus specific IgG
antibodies using the Pharmacia UNICAP in airway diseases
MCPG Schinkel, MLV Watkins, PC Potter
Conclusion
1. The Pharmacia UNICAP assay discriminates between ABPA, CF, Asthmatics and normal individuals with elevated or normal total
IgE values.
2. The highest levels were found in ABPA. These levels were 115 ± 64.32mg/L (Aspergillus fumigatus) and 84.43 ± 48.27mg/L
(Aspergillus niger).
3. Higher levels were observed in both CF and ABPA than in the other groups.
4. Both Aspergillus fumigatus and Aspergillus niger should be tested in patients with CF and ABPA, as they appear to rise
concordantly.
5. The UNICAP IgG for Aspergillus is thus a convenient automated tool in ABPA and CF.
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Valuable Clinical Information
Immunotherapy
• Show a general (but not definitive) correlation with
clinical outcome
• Show that the immune system is responding to the
therapy
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Overview of the typical
allergic response
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Specific immunotherapy
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sIgG measurement in
Specific immunotherapy Effective immunotherapy specific induces IgG/IgG4 to
the allergens
Measurement of IgG/IgG4 during the course of SIT
treatment could add information about the individual
patient beneficial response to the treatment
If a patient should not respond with an induction of
competitive antibodies during immunotherapy a careful
re-evaluation of the treatment options could be useful.
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VENOM ALLERGY
Bee and/or wasp venom allergy and indications for VIT
Discover the connectionImmunoCAP® rApi m 10 honey bee venom component
Bee and/or
wasp venom
allergy
Indications
for VIT
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Matching VIT to the patient’s sensitization profile• Successful venom immunotherapy (VIT)
is more likely when treatment selection is based on specific sensitization to bee and/or wasp venom1
“As a paradigm, allergen immunotherapy is ‘specific’, meaning
that it only modifies the immune response against the allergen
for which the vaccination is being performed.”
WAO –ARIA – GA²LEN Consensus Paper on Molecular-based Allergy Diagnostics2
Bee and/or
wasp venom
allergy
Indications
for VIT
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Double positivity – Is it a genuine bee and/or wasp venom allergy?
*Cross-reactive Carbohydrate Determinants
Positive results with venom extracts do not always reflect
genuine sensitization3
In many cases IgE antibodies to CCDs* cause double
positivity, but rarely have clinical relevance1,3,4
Up to 50% of venom allergic patients have positive test results to both bee and wasp venom3
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Double positivity – Is it a genuine bee and/or wasp venom allergy?
Genuine bee
venom allergy
Genuine wasp
venom allergy
rApi m1
rApi m10
Genuine double positivity
OR cross reactivity?
rVes v1
rVes v5
rPol d5?
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Discover the new ImmunoCAPhoney bee component rApi m 10Honey bee component Api m 10 can be absent or underrepresented in VIT extracts5 – VIT of patients sensitized to Api m 10 may be less efficient
Adding rApi m 10 to your test panel improves diagnostic specificity and precision, and supports more well-founded decisions for VIT6
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“Conclusion: Analysis of a panel of CCD-free HBV allergens improved diagnostic
sensitivity compared with use of rApi m 1 alone, identified additional major allergens,
and revealed sensitizations to allergens that have been reported to be absent or
underrepresented in therapeutic HBV preparations.”6
(n=144)
rApi m 1 + 10 improve diagnosis of genuine bee-venom sensitizationIncreases your possibility to resolve double positivity
72,2%
86,8%
60 70 80 90 100
Sensitivity (%)
rApi m 1
rApi m 1 + 10
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ImmunCAP allergen componentshelp you resolve double positivityWith five CCD-free venom components you can
• Distinguish between true co-sensitization to bee and wasp, and CCD-dependent cross reactivity1,4,7,8
- Honey bee: rApi m 1 and rApi m 10- Common/paper wasp: rVes v 1, rVes v 5, rPol d 5
• Help match the VIT to the patient’s sensitization profile1,5,6
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WAO – ARIA – GA²LEN
recommends allergen component
testing“Detection of recombinant venom allergens can discriminate
between genuine venom sensitization and cross reactivity
due to CCDs in patients with double-positive IgE results from
traditional venom tests that are based on allergen extract”
WAO – ARIA – GA²LEN Consensus Paper on Molecular-based Allergy Diagnostics2
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Identify suitable VIT – Suggested test algorithm
ImmunoCAP®
COMPLETE ALLERGENSHoney bee (i1) + Common Wasp (i3) + Paper Wasp (i77) ImmunoCAP Tryptase*
Honey bee Honey bee + Common/Paper wasp Common/Paper waspVIT CANDIDATE
ImmunoCAP
ALLERGEN COMPONENTSBee: rApi m 1 (i208), rApi m 10 (i217) Common/paper Wasp: rVes v 1(i211), rVes v 5 (i209), rPol d 5 (i210)
rApi m 1 and/or rApi m 10
positive
rApi m 1 and/or rApi m 10 + rVes v1 and/or rVes v5 and/or rPol d 5
positive positive
rVes v 1 and/or rVes v5 and/or rPol d5
positive
*Measure tryptase baseline levels before VIT to assess risk for severe reactions9
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A broad toolbox of ImmunoCAPallergen components
Over 100 allergen components that can help you:
Assess risk of systemic reactions in patients with food allergy2
Explain symptoms due to cross-reactivity2
Identify the appropriate immunotherapy for the individual patient2
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References: 1. Bonifazi F. et al & EAACI Interest Group on Insect Venom Hypersensitivity, Prevention and
treatment of hymenoptera venom allergy: guidelines for clinical practice. Allergy 2005; 60: 1459-1470. 2.
Canonica G.W. et al., A WAO - ARIA - GA²LEN consensus document on molecular-based allergy diagnostics.
World Allergy Organ J. 2013; 6(1): 17. 3. Spillner E. et al., Hymenoptera allergens: from venom to ”venome”.
Frontiers in immunology 2014; 5: 1-7. 4. Biló B. et al & EAACI Interest Group on Insect Venom
Hypersensitivity., Diagnosis of Hymenoptera venom allergy. Allergy 2005; 60: 1339-1349. 5. Blank S. et al., Api
m 10, a genuine A. mellifera venom allergen, is clinically relevant but underrepresented in therapeutic extracts.
Allergy 2011; 66: 1322-1329. 6. Köhler J et al. Component resolution reveals additional major allergens in
patients with honey bee venom allergy. J Allergy Clin Immunol 2014; 133: 1383-1389. 7. Müller U. et al.,
Hymenoptera venom allergy: analysis of double positivity to honey bee and Vespula venom by estimation of
IgE antibodies to species-specific major allergens Api m 1 and Ves v 5. Allergy 2009; 64: 543-548. 8.
Mittermann I. et al., Recombinant allergen-ased IgE testing to distinguish bee and wasp allergy. J Allergy Clin
Immunol 2010: 125: 1300-1307. 9. Rueff F et al. Predictors of severe systemic anaphylactic reactions in
patients with Hymenoptera venom allergy: Importance of baseline serum tryptase – a study of the EAACI
Interest Group on Insect Venom Hypersensitivity. J Allergy Clin Immunol 2009; 124: 1047-1054.