Franziska Roth-Walter

University of Veterinary Medicine, Vienna | vetmed · Messerli Research Institute, Department of Interdisciplinary Life Sciences

Background Beta-lactoglobulin (BLG) is a bovine lipocalin in milk with innate defense function. It is not understood under which circumstances BLG is associated with tolerance or allergy towards milk. Objective Here we assessed the capacity of ligand-free (apo-) versus -loaded (holo-) BLG to protect mice against allergy using iron-quercetin as exe...

Background Functional iron deficiency facilitates allergy development and amplifies the symptom burden in allergy sufferers. Previously micronutrients were selectively delivered to immune cells with beta-lactoglobulin as carrier (holoBLG), resulting in immune resilience and allergy prevention. Objective The clinical efficacy of a FSMP (food for sp...

Although iron is one of the most abundant elements on earth, about a third of the world's population are affected by iron deficiency. Main drivers of iron deficiency are beside the chronic lack of dietary iron, a hampered uptake machinery as a result of immune activation. Macrophages are the principal cells distributing iron in the human body with...

Nutritional Immunity is one of the most ancient innate immune responses, during which the body can restrict nutrients availability to pathogens and restricts their uptake by the gut mucosa (mucosal block). Though this can be a beneficial strategy during infection, it also is associated with non‐communicable diseases—where the pathogen is missing; l...

Background We investigated the biological function of the mould allergen Alt a 1 as a carrier of micronutrients, such as the vitamin A metabolite retinoic acid (RA) and the influence of RA binding on its allergenicity in vitro and in vivo. Methods Alt a 1‐RA complex formation was analyzed in silico and in vitro. PBMCs from Alternaria‐allergic dono...

This systematic review and meta‐analysis aimed to consolidate evidence on dietary interventions for atopic eczema/dermatitis (AD) skin symptoms in children without food allergies, following PRISMA 2020 guidelines. Systematic review updates were conducted in May 2022 and June 2023, focusing on randomized placebo‐controlled trials (RCTs) involving ch...

Food allergies (FA) consist of both IgE and non‐IgE‐mediated entities, with varying phenotypes and overlapping and different considerations for each specific disease presentation. In general, all FAs place children at increased risk for inadequate nutritional intake and negative impacts on their nutritional status, as well as negative impacts on th...

Background: We previously proposed the whey protein beta-lactoglobulin (BLG) loaded with iron-siderophore complexes as the active principle in the farm protective effect against allergies. A lozenge as food for specific medical purposes (FSMP) was formulated to assess its therapeutical efficacy in BALB/c mice and in-vitro experiments. Methods: Bind...

The accumulation of senescent cells drives inflammaging and increases morbidity of chronic inflammatory lung diseases. Immune responses are built upon dynamic changes in cell metabolism that supply energy and substrates for cell proliferation, differentiation, and activation. Metabolic changes imposed by environmental stress and inflammation on imm...

Alternaria alternata is a common fungus strongly related with severe allergic asthma, with 80% of affected individuals being sensitized solely to its major allergen Alt a 1. Here, we assessed the function of Alt a 1 as an innate defense protein binding to micronutrients, such as iron-quercetin complexes (FeQ2), and its impact on antigen presentatio...

Background: The allergists´ tool box in cat allergy management is limited. Clinical studies have shown that holo beta-lactoglobulin (holoBLG) can restore micronutritional deficits in atopic immune cells and alleviate allergic symptoms in a completely allergen-nonspecific manner. With this study, we aimed to provide proof of principle in cat allerg...

Micronutritional deficiencies are common in atopic children suffering from atopic dermatitis, food allergy, rhinitis, and asthma. A lack of iron, in particular, may impact immune activation with prolonged deficiencies of iron, zinc, vitamin A, and vitamin D associated with a Th2 signature, maturation of macrophages and dendritic cells (DCs), and th...

Bet v 1 is the major allergen in birch pollen to which up to 95% of patients sensitized to birch respond. As a member of the pathogenesis-related PR 10 family, its natural function is implicated in plant defense, with a member of the PR10 family being reported to be upregulated under iron deficiency. As such, we assessed the function of Bet v 1 to...

Ziel: Untersuchung von langfristigen Effekten durch gezielte Mikronährstoff-Supplementierung durch die holoBLG-Lutschtablette. Nachuntersuchung in der Allergenexpositionskammer (AEC) bei Patienten mit Hausstaubmilben(HSM)-assoziierter allergischer Rhinokonjunktivitis (ARC), bei denen die letzte Supplementierung mit der holoBLG-Lutschtablette vor si...

Background The immunopathogenesis of cow's milk protein allergy (CMPA) is based on different mechanisms related to immune recognition of protein epitopes, which are affected by industrial processing. Purpose The purpose of this WAO DRACMA paper is to: (i) give a comprehensive overview of milk protein allergens, (ii) to review their immunogenicity...

The immune system interacts with many nominal ‘danger’ signals, endogenous danger‐associated (DAMP), exogenous pathogen (PAMP) and allergen (AAMP)‐associated molecular patterns. The immune context under which these are received can promote or prevent immune activating or inflammatory mechanisms and may orchestrate diverse immune responses in allerg...

Background: Growing up on a cattle farm and consuming raw cow's milk protects against asthma and allergies. We expect a cattle-specific protein as active component in this farm effect. Methods: Dust was collected from cattle and poultry stables and from mattresses of households. Urine was obtained from cattle, and ambient aerosols were sampled....

Purpose The long-term effects of targeted micronutrition with the holoBLG lozenge in house dust mite (HDM) allergic rhinoconjunctivitis (ARC) patients were evaluated at a follow-up visit in an allergen exposure chamber (AEC). Methods Patients who were supplemented for 3‑months with the holoBLG lozenge in a previous study with two controlled HDM-AE...

Background Previously, the protective farm effect was imitated using the whey protein beta-lactoglobulin (BLG) that was spiked with iron-flavonoid complexes. Here, we formulated for clinical translation a lozenge as food for specific medical purposes (FSMP) using catechin-iron complexes as ligands for BLG. The lozenge was tested in vitro and in a t...

Background: Epidemiological studies suggest that allergy is associated with iron deficiency. We sought to determine and compare iron and microbial parameters of allergic and non-allergic women without anemia and associated them with their clinical response upon nasal provocation. Methods: Female subjects (27 allergics, 24 non-allergic) donated bl...

Eisenmangel ist mit Atopie assoziiert. So erhöht Eisenmangel während der Schwangerschaft, das Risiko bei Kindern, eine atopische Erkrankung zu entwickeln, und sowohl allergische Kinder als auch Erwachsene leiden eher an einer Eisenmangel-Anämie als Nicht-Allergiker. Immunologisch gesehen, aktiviert Eisenmangel zuerst das Immunsystem, indem es eine...

Ziel: Evaluierung einer Lutschtablette zur Mikronährstoff-Supplementierung basierend auf dem Bauernhof-Effekt, bei Patienten mit Hausstaubmilben(HDM)- assoziierter allergischer Rhinokonjunktivitis (ARC) in einer standardisierten Allergen-Expositionskammer (AEC). Methoden: Vor (V1) und nach (V3) täglicher Supplementierung mit holo-BLG (BLG, β-Lactog...

Recent epidemiological studies link iron deficiency with atopy. Iron deficiency during pregnancy increases the risk in children for atopic diseases. The risk to develop anemia is also increased in allergic subjects. Iron deficiency can activate immune cells, leads to expansion of Th2 but not Th1 cells, and promotes B cell class switch. As such, iro...

Iron deficiency is associated with atopy. Iron deficiency during pregnancy increases the risk of atopic diseases in children, while both allergic children and adults are more likely to have iron deficiency anemia. Immunologically, iron deficiency leads to activation of antigen-presenting cells, promotion of Th2 cells and enables antibody class swit...

One Health is “a collaborative effort of multiple disciplines – working locally, nationally, and globally – to attain optimal health for people, animals, and the environment”, the so‐called One Health triad1 (Fig. 1).Historically, aspects of One Healthwere already discussed in the fourth century by Hippocrates, who realized that a clean environment...

The lipocalin beta-lactoglobulin (BLG) is a major protein compound in cow’s milk, and we detected it in cattle stable dust. BLG may be a novel player in the farm protective effect against atopic sensitization and hayfever. In previous studies, we demonstrated that only the ligand-filled holo-form of BLG prevented sensitization to itself. Here, we i...

Allergen immunotherapy (AIT) is the only setting in which a vaccine is applied in patients allergic exactly to the active principle in the vaccine. Therefore, AIT products need to be not only effective but also safe. In Europe, for subcutaneous AIT, this has been achieved by the allergoid strategy in which IgE epitopes are destroyed or masked. In a...

Evaluation of a lozenge for targeted micronu-trition (holo-BLG), a new invention based on the farm effect, in house dust mite (HDM) allergic rhinocon-junctivitis (ARC) patients in a standardized allergen exposure chamber (AEC). Eligible HDM allergic patients were exposed to HDM raw material in an AEC for 120 min before (V1) and after (V3) 3 months...

Therapeutic advances using targeted biologicals and small‐molecule drugs have achieved significant success in the treatment of chronic allergic, autoimmune, and inflammatory diseases particularly for some patients with severe, treatment‐resistant forms. This has been aided by improved identification of disease phenotypes. Despite these achievements...

Abstract Elevated serum IgE levels are associated with allergic disorders, parasitosis and specific immunologic abnormalities. In addition, epidemiological and mechanistic evidence indicates an association between IgE-mediated immune surveillance and protection from tumour growth. Intriguingly, recent studies reveal a correlation between IgE defici...

This is a position paper of The European Academy of Allergy /EAACI, and the first time report that ultra-low IgE is a biomarker in Cancer.

Since the introduction of allergen immunotherapy (AIT) over 100 years ago, focus has been on standardization of allergen extracts, with reliable molecular composition of allergens receiving the highest attention. While adjuvants play a major role in European AIT, they have been less well studied. In this Position Paper, we summarize current unmet n...

Worldwide 300 million children and adults are affected by asthma. The development of asthma is influenced by environmental and other exogenous factors synergizing with genetic predisposition, and shaping the lung microbiome especially during birth and in very early life. The healthy lung microbial composition is characterized by a prevalence of bac...

The present patent relates to the use of bioadhesive, biodegradable poly‐lacto‐glycolic (PLGA) microparticles for allergen immunotherapy. Surface modification of allergen‐loaded microspheres with Aleuria aurantia lectin causes selective enrichment, prolongation of the dwell time and uptake via mucosal M cells overlying the lymph nodes e.g. in tonsi...

The microbiota can play important roles in the development of human immunity and the establishment of immune homeostasis. Lifestyle factors including diet, hygiene, and exposure to viruses or bacteria, and medical interventions with antibiotics or anti‐ulcer medications, regulate phylogenetic variability and the quality of cross talk between innate...

Chronic airway diseases such as asthma and chronic obstructive pulmonary disease (COPD), together with their comorbidities, bear a significant burden on public health. Increased appreciation of molecular networks underlying inflammatory airway disease needs to be translated into new therapies for distinct phenotypes not controlled by current treatm...

Abstract Background So far, only a few biomarkers in allergen immunotherapy exist that are associated with a clinical benefit. We thus investigated in a pilot study whether innate molecules such as the molecule lipocalin-2 (LCN2), with implications in immune tolerance demonstrated in other fields, may discriminate A) between allergic and non-allerg...

Background Macrophages can be converted in vitro into immunoregulatory M2b macrophages in the presence of immune complexes (ICs), but the role of the specific subclasses IgG1 or IgG4 in this phenotypic and functional change is not known. Objective We aimed to refine the original method by applying precisely defined ICs of the subclasses IgG4 or Ig...

In human patients with seasonal allergic rhinoconjunctivitis sensitized to grass pollen, the first successful allergen immunotherapy (AIT) was reported in 1911. Today, immunotherapy is an accepted treatment for allergic asthma, allergic rhinitis and hypersensitivities to insect venom. AIT is also used for atopic dermatitis and recently for food all...

To improve current mucosal allergen immunotherapy Vibrio cholerae neuraminidase (NA) was evaluated as a novel epithelial targeting molecule for functionalization of allergen-loaded, poly(D,L-lactide-co-glycolide) (PLGA) microparticles (MPs) and compared to the previously described epithelial targeting lectins wheat germ agglutinin (WGA) and Aleuria...

The major cow's milk allergen Bos d 5 belongs to the lipocalin protein family, with an intramolecular pocket for hydrophobic ligands. We investigated whether Bos d 5 when loaded with the active vitamin A metabolite retinoic acid (RA), would elicit differential immune responses compared to the unloaded state. By in silico docking an affinity energy...

Atopic individuals tend to develop a Th2 dominant immune response, resulting in hyperresponsiveness to harmless antigens, termed allergens. In the last decade, epidemiological studies have emerged that connected allergy with a deficient iron-status. Immune activation under iron-deficient conditions results in the expansion of Th2-, but not Th1 cell...

While desired for the cure of allergy, regulatory immune cell subsets and non-classical Th2-biased inflammatory mediators in the tumour microenvironment can contribute to immune suppression and escape of tumours from immunological detection and clearance. A key aim in the cancer field is therefore to design interventions that can break immunologica...

Purpose of review: Animal studies published within the past 18 months were assessed, focusing on innate and specific immunomodulation, providing knowledge of high translational relevance for human atopic and allergic diseases. Recent findings: Allergic companion animals represent alternative models, but most studies were done in mice. Atopic der...

In chronically damaged tissue, trefoil factor family (TFF) peptides ensure epithelial protection and restitution. In chronic kidney disease (CKD), TFF1 and TFF2 are reported to be upregulated. Especially in the early phase, CKD is associated with silently ongoing renal damage and inflammation. Moreover, many patients are diagnosed late during disea...

Acrolein, a highly reactive unsaturated aldehyde, is generated in large amounts during smoking and is best known for its genotoxic capacity. Here, we aimed to assess whether acrolein at concentrations relevant for smokers may also exert immunomodulatory effects that could be relevant in allergy or cancer. In a BALB/c allergy model repeated nasal ex...

Purpose of review: Animal models published within the past 18 months on asthma, food allergy and anaphylaxis, all conditions of rising public health concern, were reviewed. Recent findings: While domestic animals spontaneously develop asthma, food allergy and anaphylaxis, in animal models, divergent sensitization and challenge routes, dosages, i...

Inflammatory bowel disease (IBD) is a group of chronic inflammatory conditions of the gastrointestinal tract. In humans, two major types exist: Crohn’s disease and ulcerative colitis. Similarly, also pets can suffer from IBD having predominantly lymphocytic-plasmacytic enteritis/colitis, but also eosinophilic enteritis/colitis is common. Accumulati...

Cinnamon aldehyde (alias cinnamaldehyde) is widely used in food, textile or cosmetic industry. It is mostly associated with contact allergy, but immediate type allergies have been reported. The present study was triggered by a case of anaphylactic events to cinnamon in food and upon skin prick test. We investigated a possible correlation of exposur...

Background: Anticancer vaccines could represent a valuable complementary strategy to established therapies, especially in settings of early stage and minimal residual disease. HER-2 is an important target for immunotherapy and addressed by the monoclonal antibody trastuzumab. We have previously generated HER-2 mimotope peptides from phage display...

Figure S1. 3D structure and topology of a prototypical lipocalin.

Background: Chemokine ligand 20 (CCL20) is a chemokine released by mainly liver and blood leucocytes. Particularly under pro-inflammatory circumstances it triggers chemotaxis of lymphocytes and dendritic cells via activating receptor chemokine receptor 6 (CCR6) that is specific to it. In experimental sepsis models, the chemokine-receptor pair has...

Owners and their domestic animals via skin shedding and secretions, mutually exchange microbiomes, potential pathogens and innate immune molecules. Among the latter especially lipocalins are multifaceted: they may have an immunomodulatory function and, furthermore, they represent one of the most important animal allergen families. The amino acid id...

The authors regret that the wrong method of body temperature measurement was indicated. The correct method is given below. The authors affirm that this change does by no way affect the results of any of the experiments and findings of the study. 2.6. Measurement of body temperature On day 70 (sacrifice), mice were challenged intravenously with Ara...

Chronic kidney disease (CKD) is associated with high morbidity and mortality. In many patients CKD is diagnosed late during disease progression. Therefore, the implementation of potential biomarkers may facilitate the early identification of individuals at risk. Trefoil factor family (TFF) peptides promote restitution processes of mucous epithelia...

Background: We revealed in previous studies that nitration of food proteins reduces the risk of de novo sensitization in a murine food allergy model. In contrast, in situations with preformed specific IgE antibodies, in vitro experiments suggested an increased capacity of effector cell activation by nitrated food proteins. Objective: The aim of...

The allergenic potential of proteins can be altered under various physicochemical conditions. Glutathione (GSH) is a reducing agent that is used as an antioxidant in food products. We aimed to characterize the natural folding of peach proteins and test the allergenicity of reduced and natural Pru p 3, the major peach allergen. Pru p 3 was purified...

Background Besides its anti-inflammatory effects, cinnamaldehyde has been reported to have anti-carcinogenic activity. Here, we investigated its impact on immune cells. Methods Activation of nuclear factor-κB by cinnamaldehyde (0–10 µg/ml) alone or in combination with lipopolysaccharide was assessed in THP1XBlue human monocytic cell line and in hu...

The mechanisms of allergic sensitization to milk are still elusive. The major allergen Bos d 5 belongs to the lipocalin-family and thus is able to transport numerous ligands. In this study we investigated its ability to bind to iron-siderophore complexes and tested the immune-modulatory properties of Bos d 5 in either forms. Structural and in silic...

It is hypothesized that allergens are at the borderline of self and non-self and, through as yet elusive circumstances, mount a Th2 response for allergic sensitization. The major birch pollen allergen Bet v 1 is considered the prototype for the PR-10 protein family causing respiratory allergy. Here, we give structural evidence that Bet v 1 is a lip...

The present invention relates to the use of neutrophil gelatinase-associated lipocalin (NGAL=LCN2=24p3) as as a diagnostic tool for allergy and as a therapeutic method of treating, reducing, or ameliorating clinical manifestations of allergic disease. The invention includes measurement of NGAL levels in body fluids such as serum/plasma/saliva/blood...

Abstract for Section 13.1 The immune system has the challenging tasks to discriminate self from non-self, but also to discern harmless from harmful foreign antigens or entities and to attack and eliminate foreign threats. In the classical view the immune system can be divided into an innate and adaptive branch, where the innate immune system repres...

In spite of the fact that human medicine and veterinary medicine share a long history of mutual fertilization, the number of interactions between these disciplines is still insufficient today. To foster the interdisciplinary dialogue for the sake of human and animal patients, this book of Comparative medicine was created. In this first book, compar...

All organisms evolved mechanisms to protect themselves against pathogen invasion and hence possess an innate immune system. However, vertebrates have also evolved an additional strategy, the so-called adaptive immune system to further protect themselves against pathogens. In the classical view the immune system can be divided into an innate and ada...

Neutrophil gelatinase associated lipocalin (NGAL) protein is attracting a great interest because of its antibacterial properties played upon modulating iron content in competition against iron acquisition processes developed by pathogenic bacteria that bind selective ferric iron chelators (siderophores). Besides its known high affinity to enterobac...

Background The egg allergen ovomucoid (Gal d 1) is conformationally stabilized by 9 disulfide bonds. However, patients with persistent egg-allergy have more IgE against sequential than conformational epitopes of ovomucoid. We investigated whether natural or added food compounds may cause reduction of disulfide bonds and linearization of ovomucoid....