Allergy Update. because you depend upon results. Abacus ALS

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Allergy Update Abacus ALS ALS

ImmunoCAP sigg measurement

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.

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.

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

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.

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.

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

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

Prospective cohort study of 175 adult patients with chronic or allergic pulmonary aspergillosis. Aspergillus IgG antibodies detected using CIE, Phadia ImmunoCap Aspergillus IgG and Bio-Rad Platelia Aspergillus IgG.

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 Platelia IgG 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 ImmunoCap IgG 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.

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.

Valuable Clinical Information Immunotherapy Show a general (but not definitive) correlation with clinical outcome Show that the immune system is responding to the therapy

Overview of the typical allergic response

Specific immunotherapy

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.

Bee and/or wasp venom allergy VENOM ALLERGY Indications for VIT Bee and/or wasp venom allergy and indications for VIT Discover the connection ImmunoCAP rapi m 10 honey bee venom component

Bee and/or wasp venom allergy Indications for VIT 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 venom 1 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 Diagnostics 2

Double positivity Is it a genuine bee and/or wasp venom allergy? Up to 50% of venom allergic patients have positive test results to both bee and wasp venom 3 Positive results with venom extracts do not always reflect genuine sensitization 3 In many cases IgE antibodies to CCDs* cause double positivity, but rarely have clinical relevance 1,3,4 *Cross-reactive Carbohydrate Determinants

Double positivity Is it a genuine bee and/or wasp venom allergy? rapi m1 rves v1 Genuine bee venom allergy rapi m10? rpol d5 rves v5 Genuine wasp venom allergy Genuine double positivity OR cross reactivity?

Discover the new ImmunoCAP honey bee component rapi m 10 Honey bee component Api m 10 can be absent or underrepresented in VIT extracts 5 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 VIT 6

rapi m 1 + 10 improve diagnosis of genuine bee-venom sensitization Increases your possibility to resolve double positivity rapi m 1 rapi m 1 + 10 72,2% 86,8% (n=144) 60 70 80 90 100 Sensitivity (%) 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

ImmunCAP allergen components help you resolve double positivity With five CCD-free venom components you can Distinguish between true co-sensitization to bee and wasp, and CCD-dependent cross reactivity 1,4,7,8 - 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 profile 1,5,6

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 Diagnostics 2

Identify suitable VIT Suggested test algorithm ImmunoCAP COMPLETE ALLERGENS Honey bee (i1) + Common Wasp (i3) + Paper Wasp (i77) ImmunoCAP Tryptase* ImmunoCAP ALLERGEN COMPONENTS Bee: 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 VIT CANDIDATE Honey bee Honey bee + Common/Paper wasp Common/Paper wasp *Measure tryptase baseline levels before VIT to assess risk for severe reactions 9

A broad toolbox of ImmunoCAP allergen components Over 100 allergen components that can help you: Assess risk of systemic reactions in patients with food allergy 2 Explain symptoms due to cross-reactivity 2 Identify the appropriate immunotherapy for the individual patient 2

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.