Rekombinante Allergene: Routinediagnostik oder Wissenschaft?

Zusammenfassung: Die Verwendung rekombinanter Allergenkomponenten eröffnet mehrere diagnostische Möglichkeiten. So können krankheitsspezifische Sensibilisierungsmuster wie etwa bei der allergisch bronchopulmonalen Aspergillose ABPA identifiziert werden. Durch Bestimmung der Majorallergene wichtiger Pollen (Betv1, Ole1, Phlp1/Phlp5) kann eine präzisere Indikationsstellung im Hinblick auf eine allergenspezifische Immuntherapie ermöglicht werden, da Extrakte v.a. Majorallergene enthalten. Sensibilisierungen auf Nebenallergene wie Profiline und Polcalcine beeinflussen aufgrund der großen Kreuzreaktivität herkömmliche IgE-Tests, sind aber oft von untergeordneter klinischer Bedeutung. Bei Nahrungsmitteln können häufige Kreuzreaktionen etwa mit Birkenpollen über Betv1/PR-10-Proteine nachgewiesen werden. Zudem lassen Sensibilisierungen auf Speicherproteine etwa von Erdnuss (Arah2) oder Lipidtransferproteine von Pfirsich (Prup3) oder Haselnuss (Cora8) Rückschlüsse auf ein höheres Anaphylaxierisiko zu. Anstrengungsinduzierte Beschwerden (Tria19), unklare Latexsensibilisierungen oder Doppelpositivität bei Insektengiftallergien sind weitere aktuell sinnvolle Einsatzgebiete. Microarray-basierte Allergenchips erlauben bereits heute die Bestimmung von IgE gegen über 100Allergenen aus kleinsten Serummengen, bedürfen aber noch der Evaluation und Optimierung bezüglich Allergenauswahl und Sensitivitä

Decreased skin colonization with Malassezia spp. and increased skin colonization with Candida spp. in patients with severe atopic dermatitis

Background: Atopic dermatitis (AD) is a chronic relapsing inflammatory skin disease in which patients are sensitized towards a plethora of allergens. The hosts fungal microbiota, the mycobiota, that is believed to be altered in patients suffering from AD acts as such an allergen. The correlation context of specific sensitization, changes in mycobiota and its impact on disease severity however remains poorly understood. Objectives: We aim to enhance the understanding of the specific sensitization towards the mycobiota in AD patients in relation to their fungal skin colonization. Methods: Sensitization pattern towards the Malassezia spp. and Candida albicans of 16 AD patients and 14 healthy controls (HC) were analyzed with the newly developed multiplex-assay ALEX2® and the established singleplex-assay ImmunoCAP®. We compared these findings with the fungal skin colonization analyzed by DNA sequencing of the internal transcribed spacer region 1 (ITS1). Results: Sensitization in general and towards Malassezia spp. and C. albicans is increased in AD patients compared to HC with a quantitative difference in severe AD when compared to mild to moderate AD. Further we saw an association between sensitization towards and skin colonization with Candida spp. yet a negative correlation between sensitization towards and skin colonization with Malassezia spp. Conclusion: We conclude that AD in general and severe AD in particular is associated with increased sensitization towards the hosts own mycobiota. There is positive correlation in Candida spp. skin colonization and negative in Malassezia spp. skin colonization when compared to AD, AD severity as well as to specific sensitization patterns

Potential Cost Savings by Switching from Subcutaneous to Intralymphatic Insect Venom Immunotherapy

Introduction: IgE-mediated bee venom allergy can be treated with allergen-specific immunotherapy (AIT). Subcutaneous immunotherapy (SCIT) is time and cost intensive due to the repeated consultations, but the costs are justified by the high risk of potentially life-threatening allergic reactions, including anaphylaxis. However, intralymphatic immunotherapy (ILIT) offers potential to reduce treatment costs due to a significant reduction in injections and a shorter duration of therapy. Therefore, we calculated the cost savings that arise when switching from SCIT to ILIT. Methods: Treatment protocols for ILIT were based on previous ILIT studies. Treatment protocols for SCIT were based on routine treatment at the University Hospital Zurich (USZ). The treatment costs were calculated based on the internal hospital information system (KISIM). Results: The calculations revealed a potential two-fold reduction in treatment costs if ILIT is used instead of SCIT in patients with bee venom allergy. The costs could be reduced from EUR 11,612.59 with SCIT to EUR 5,942.15 with ILIT over 5 years. Conclusions: This study shows that bee venom ILIT has a cost-benefit potential for health insurances and patients, which should encourage further ILIT studies and which should be taken into account when considering future implementation of ILIT in the standard care of venom allergy

Dysbiosis of skin microbiota with increased fungal diversity is associated with severity of disease in atopic dermatitis

Background: Atopic dermatitis (AD) is a multifactorial inflammatory skin disease and an altered skin microbiota with an increase of Staphylococcus aureus has been reported. However, the role of fungi remains poorly investigated. Objectives: We aimed to improve the understanding of the fungal skin microbiota, the mycobiota, in AD in relation to the bacterial colonization. Methods: Skin swabs of 16 AD patients and 16 healthy controls (HC) from four different skin sites, that is antecubital crease, dorsal neck, glabella and vertex from multiple time points were analysed by DNA sequencing of the internal transcribed spacer region 1 (ITS1) and 16S rRNA gene for fungi and bacteria, respectively. Results: Malassezia spp. were the predominant fungi in all subjects but with a decreased dominance in severe AD patients in favour of non-Malassezia fungi, for example Candida spp. For bacteria, a decrease of Cutibacterium spp. in AD patients in favour of Staphylococcus spp., particularly S. aureus, was observed. Further, both bacterial and fungal community compositions of severe AD patients significantly differed from mild-to-moderate AD patients and HC with the latter two having overall similar microbiota showing some distinctions in bacterial communities. Conclusions: We conclude that severe AD is associated with a pronounced dysbiosis of the microbiota with increased fungal diversity. Potentially infectious agents, for example Staphylococcus and Candida, were increased in severe AD. Keywords: atopic dermatitis; bacteria; disease severity; fungi; skin microbiot

IgE-mediated sensitization to malassezia in atopic dermatitis: More common in male patients and in head and neck type

BACKGROUND: Atopic dermatitis (AD) is a common chronic inflammatory skin disease. Malassezia, the predominant skin microbiota fungus, is considered to exacerbate AD, especially in a subset of patients with head and neck type AD (HNAD). In the present study, the relationship between AD and sensitization to Malassezia antigens was investigated. METHODS: We assessed 173 patients with AD. The severity of eczema was determined with Eczema Area and Severity Index (EASI); the type of AD, namely, head and neck type, was reported as well. The total serum IgE and specific IgE to Malassezia were determined and correlated with clinical picture of AD, sex, age, and the EASI. RESULTS: Total IgE was elevated in 77.7% of patients. Specific IgE to Malassezia was positive (≥0.35 kU/L) in 49.1% of patients. Men were significantly more often sensitized to Malassezia antigen (58% of men vs 42% of women; P value, 0.04). Concurrently, 58% of patients with HNAD versus 42% non-HNAD patients had higher levels of specific IgE to Malassezia, this difference being nearly significant (P value, 0.06). Patients with atopy were also more frequently sensitized to Malassezia. No significant relationship between EASI and the level of total IgE or specific IgE to Malassezia was observed. CONCLUSIONS: In our population, IgE-mediated sensitization was found in up to 49% of all patients with AD, most common in men and in head and neck type