Birch pollen-related food allergies : clinical, epidemiological and immunological aspects

Patients suffering from respiratory birch pollen allergy are also known to be allergic to some foods; for example, stone-fruits, hazelnuts, and some vegetables. The aim of this thesis was to explore clinical and immunological characteristics of birch pollen-related food allergy. To obtain more clinical information on birch pollen-related food allergies, we analyzed data about the symptoms of Austrian birch pollen-allergic patients (N=225) to particular foods. More than 70% of the study participants indicated that they experienced birch pollen-related food allergy and more than 87% of these food-allergic patients suffered not only during the birch pollen season, but perennially. Apple, hazelnut, and peach were found to most frequently provoke symptoms of the birch pollen-related food allergies, mainly causing oral allergy syndrome. The major birch pollen allergen Bet v 1 was determined as the allergen to which patients with birch pollen-related food allergies are primarily sensitized, whereas the pan-allergen profilin (Bet v 2) was determined to be less relevant. To obtain more knowledge about immune mechanisms of birch pollen-related food allergies, we explored the function of allergen-specific IgG4 antibodies in immunological cascades of birch pollen-allergic patients who tolerate birch pollen-related foods. We found that individual food-specific IgG4/IgE ratios were significantly higher in patients tolerating either apple or hazelnut than in individuals with an allergy to these foods. Next, recombinant (r) Bet v 1 and rMal d 1, the Bet v 1-homolog in apple, were applied sublingually in allergic patients to study the immune effects in vivo. Sublingual administration of rBet v 1 or rMal d 1 was associated with a transient induction of immune tolerance, possibly mediated by IL-10+Foxp3+ T cells with suppressive function. In addition, we found that rMal d 1 activated T cells with different epitope specificities and effector functions as compared to rBet v 1 in vivo. In summary, this PhD thesis provides new insights into clinical and pathophysiological aspects of birch pollen-related food allergy. These insights could be implemented for further developments of diagnostic concepts and effective treatment strategies for this highly relevant food allergy.Birkenpollen-Allergiker entwickeln oft neben respiratorischen Symptomen allergische Reaktionen auf bestimmte Nahrungsmittel, z. B. auf Steinobst, Haselnüsse und bestimmte Gemüsesorten. Das Ziel dieser Arbeit war es, klinische und immunologische Aspekte dieser sekundären Nahrungsmittelallergie zu untersuchen. Um mehr Information über die klinischen Aspekte der Birkenpollenassoziierten Nahrungsmittelallergie zu erhalten, haben wir Daten von mehr als 200 Birkenpollen-Allergikern analysiert. Mehr als 70% dieser Personen berichteten, an der Birkenpollen-assoziierten Nahrungsmittelallergie zu leiden; mehr als 87% ganzjährig, d. h. auch außerhalb der Birkenpollen-Saison. Apfel, Haselnuss und Pfirsich wurden als die wichtigsten Auslöser für die Birkenpollen-assoziierte Nahrungsmittelallergie festgestellt, wobei sie hauptsächlich das Orale Allergiesyndrom verursachten. Das Birkenpollen- Hauptallergen Bet v 1 wurde als primärer Initiator für diese Nahrungsmittelallergie identifiziert, während das Panallergen Profilin (Bet v 2) sich als weniger relevant erwies. Um mehr Einblick in die immunologischen Aspekte der Birkenpollenassoziierten Nahrungsmittelallergie zu erhalten, haben wir die Rolle der Allergen-spezifischen IgG4-Antikörper für die Toleranz gegenüber Birkenpollenassoziierten Nahrungsmitteln untersucht. Wir haben beobachtet, dass das Verhältnis von Nahrungsmittel-spezifischem IgG4 zu IgE bei jenen Patienten, die entweder Apfel oder Haselnuss tolerieren, signifikant höher war als bei Patienten mit Nahrungsmittelallergien. Außerdem haben wir rekombinantes (r)Bet v 1 und rMal d 1, das Bet v 1-Homolog in Äpfeln, sublingual verabreicht und allergen-induzierte Effekte in vivo analysiert. Die sublinguale Verabreichung von rBet v 1 oder rMal d 1 wurde von einer vorübergehenden Induktion der peripheren Toleranz (möglicherweise durch IL-10+Foxp3+ T-Zellen mit suppressiver Kapazität) begleitet. Des Weiteren haben wir beobachtet, dass rMal d 1 im Vergleich zu rBet v 1 T-Zellen mit unterschiedlichen Epitop- Spezifitäten und Effektorfunktionen in vivo induziert hat. Zusammenfassend bietet diese Dissertation neue Einblicke in die immunologischen Mechanismen der Birkenpollen-assoziierten Nahrungsmittelallergie, die Grundlage für die künftige Entwicklung effektiver Behandlungsstrategien für diese sehr relevante Nahrungsmittelallergie bilden.submitted by Marija Geroldinger-SimicAbweichender Titel laut Übersetzung der Verfasserin/des VerfassersZsfassung in dt. SpracheWien, Med. Univ., Diss., 2013OeBB(VLID)171419

Immunogenicity Parameters of Cancer Patients Receiving the mRNA Vaccine BNT162b2 While Obtaining Radiotherapy: A Longitudinal Cohort Evaluation

Background: Cancer patients are highly prone to infectious diseases. While undergoing antineoplastic treatment, the risk of severe symptoms upon infection increases, necessitating efficient protective measures, such as vaccination. For patients receiving radiotherapy, there is no specific information about humoral immunity. During the COVID-19 pandemic, serial antibody measurements were therefore offered to cancer patients, following SARS-CoV-2 vaccination while obtaining radiotherapy. Methods: Out of 74 enrolled patients, 46 met the inclusion criteria. Two cohorts were allocated, depending on an association with chemotherapy or pure radiotherapy. An additional healthy control cohort of 16 healthcare workers was enrolled. All participants followed a two-fold BNT162b2 vaccine schedule. SARS-CoV-2 binding antibodies were measured serially in a 7-day cycle for 35 days and over the long-term, using the Elecsys® Anti-SARS-CoV-2 immunoassay. Results: Cancer patients under pure radiotherapy have a comparable humoral vaccination response and long-term persistency of antibodies to healthy controls. Patients receiving additional chemotherapy show a significantly delayed immune response and decreased antibody titers. The vaccine was well tolerated in all cohorts. Conclusions: Pure radiotherapy in cancer patients does not interfere with the vaccine-induced humoral immune response or other immunogenetic aspects, whereas previous or simultaneous chemotherapy does. Findings are of particular relevance for future epidemic or pandemic scenarios

Cutaneous manifestations, clinical characteristics, and prognosis of patients with systemic sclerosis sine scleroderma : data from the International EUSTAR Database

IMPORTANCE Systemic sclerosis (SSc) sine scleroderma (ssSSc) is a subset of SSc defined by the absence of skin fibrosis. Little is known about the natural history and skin manifestations among patients with ssSSc. OBJECTIVE To characterize the clinical phenotype of patients with ssSSc compared with patients with limited cutaneous SSc (lcSSc) and diffuse cutaneous SSc (dcSSc) within the EUSTAR database.DESIGN, SETTING, AND PARTICIPANTS This longitudinal observational cohort study based on the international EUSTAR database included all patients fulfilling the classification criteria for SSc assessed by the modified Rodnan Skin score (mRSS) at inclusion and with at least 1 follow-up visit; ssSSc was defined by the absence of skin fibrosis (mRSS = 0 and no sclerodactyly) at all available visits. Data extraction was performed in November 2020, and data analysis was performed from April 2021 to April 2023.MAIN OUTCOMES AND MEASURES Main outcomes were survival and skin manifestations (onset of skin fibrosis, digital ulcers, telangiectasias, puffy fingers).RESULTS Among the 4263 patients fulfilling the inclusion criteria, 376 (8.8%) were classified as having ssSSc (mean [SD] age, 55.3 [13.9] years; 345 [91.8%] were female). At last available visit, in comparison with 708 patients with lcSSc and 708 patients with dcSSc with the same disease duration, patients with ssSSc had a lower prevalence of previous or current digital ulcers (28.2% vs 53.1% in lcSSc; P 40%) and SSc renal crisis (almost 3%). Patients with ssSSc had a higher survival than other subsets. Dermatologists should be aware that cutaneous findings in this subgroup may be associated with internal organ dysfunction. In particular, skin telangiectasias in ssSSc were associated with diastolic heart dysfunction

Systemic sclerosis-associated interstitial lung disease in the EUSTAR database : analysis by region

Objectives The prevalence and characteristics of SSc-associated interstitial lung disease (SSc-ILD) vary between geographical regions worldwide. The objectives of this study were to explore the differences in terms of prevalence, phenotype, treatment and prognosis in patients with SSc-ILD from predetermined geographical regions in the EUSTAR database. Material and methods Patients were clustered into seven geographical regions. Clinical characteristics and survival of patients with SSc-ILD were compared among these pre-determined regions. Results For baseline analyses, 9260 SSc patients were included, with 6732 for survival analyses. The prevalence of SSc-ILD in the overall population was 50.2%, ranging from 44.0% in 'Western Europe and Nordic countries' to 67.5% in 'Eastern European, Russia and Baltic countries'. In all regions, anti-topoisomerase antibodies were associated with SSc-ILD. Management also significantly differed; mycophenolate mofetil was prescribed at baseline in 31.6% of patients with SSc-ILD in 'America (North and South)' and 31.7% in 'Middle East' but only 4.3% in 'Asia and Oceania' (P <0.0001). Patients from 'America (North and South)' and 'Middle East' had the highest survival rate at the end of follow-up (85.8% and 85.2%, respectively). Conclusions Our study highlights key differences among regions in terms of clinical presentation and prognosis of SSc-ILD. This work also demonstrates that the management of SSc-ILD is highly variable among the different regions considered, suggesting that efforts are still needed for the standardization of medical practice in the treatment of this disease