Gewählte Publikation:
Koch, L.
Molecular allergy diagnostics is highly sensitive and prevents misdiagnosis in patients sensitized to aeroallergens
Doktoratsstudium der Medizinischen Wissenschaft; Humanmedizin; [ Dissertation ] Medizinische Universität Graz; 2022. pp. 108
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- Autor*innen der Med Uni Graz:
- Betreuer*innen:
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Aberer Werner
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Böhm Eva
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Sturm Gunter
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- Abstract:
- Background: Allergen immunotherapy is the only causal treatment of respiratory allergy. Identifying the correct allergens is necessary to prescribe effective immunotherapies; however, the specificity of extract-based allergy diagnosis is impaired by cross-reactivity due to cross-reactive carbohydrate determinants (CCDs), profilins, or polcalcins. Consequently, cross-reactivity may lead to misdiagnosis and the prescription of wrong immunotherapies. Molecular allergy diagnostics (MAD) may avoid the confounding effects of cross-reactivity. This thesis aimed to investigate the reliability of MAD with different commercially available methods to diagnose allergy to house dust mite (HDM) and the six most common seasonal allergens in Austria: Alternaria and pollen of ash, birch, timothy grass, mugwort and ragweed.
Methods: First, 215 patients were investigated to determine the sensitivity of molecular HDM allergy diagnosis using four different test methods. In the second part, the incidence of multiple pollen-sensitization was analyzed in 2,948 patients. In 600 of these patients, the prevalence of cross-reactivity was explored. In addition, sensitivity and specificity of seasonal molecular allergy diagnosis were investigated in 742 patients using two different test methods.
Results: The sensitivities of molecular tests were correlated to allergen-specific immunoglobulin E (sIgE) levels to the extract. The overall sensitivity to diagnose HDM allergy using at least Der p 1, 2 and 23 ranged between 93.0% and 94.9%, depending on the method performed. Pollen allergy was prevalent in our study population. 1,627 patients (55.2%) were positive to at least one, and 1,002 patients (34.0%) were positive to more than one of the five pollen allergens investigated. About one tenth (10.2%) of all patients referred to allergy diagnosis, and nearly one-fifth (18.5%) of all pollen-allergic patients had reactivity to at least one cross-reactive allergen (CCDs, profilin or polcalcin) and were therefore at potential risk of misdiagnosis. The sensitivity of seasonal MAD was high, with sensitivities between 96.2% and 100% using ImmunoCAP and 91.5% and 100% using ALEX2. Besides Art v 1 determined with ALEX2 in sera with low mugwort-extract levels, all molecular allergens (Alt a 1, Amb a 1, Art v 1, Bet v 1, Fra / Ole e 1, Phl p 1 and 5) performed statistically equally to extract-based diagnosis in both methods. Specificity was 100% for both platforms and all seasonal molecular marker allergens.
Conclusions: MAD using commercially available methods is a sensitive, specific and reliable technique to diagnose HDM and seasonal aeroallergens. MAD helps to avoid misdiagnosis and to correctly select primary allergen sources for immunotherapy.