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Microbiota composition and associated metabolic activities are essential for the education and development of a healthy immune system. Microbial dysbiosis, caused by risk factors such as diet, birth mode, or early infant antimicrobial therapy, is associated with the inception of allergic diseases. In turn, allergic diseases increase the risk for irrational use of antimicrobial therapy. Microbial therapies, such as probiotics, have been studied in the prevention and treatment of allergic diseases, but evidence remains limited due to studies with high heterogeneity, strain-dependent effectiveness, and variable outcome measures. In this review, we sketch the relation of microbiota with allergic diseases, the overuse and rationale for the use of antimicrobial agents in allergic diseases, and current knowledge concerning the use of bacterial products in allergic diseases. We urgently recommend 1) limiting antibiotic therapy in pregnancy and early childhood as a method contributing to the reduction of the allergy epidemic in children and 2) restricting antibiotic therapy in exacerbations and chronic treatment of allergic diseases, mainly concerning asthma and atopic dermatitis. Future research should be aimed at antibiotic stewardship implementation strategies and biomarker-guided therapy, discerning those patients that might benefit from antibiotic therapy.

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This review highlights the novelties in understanding the underlying immunologic mechanisms of drug hypersensitivity reactions (DHRs) with special reference to beta-lactams (BLs) in the pediatric population, as well as tiny changes in clinical classification and diagnosis of DHRs, in the last couple of years. BLs are still the most commonly prescribed and used antibiotics in children. Viral infections are very often in children, and they can provoke skin rashes which are difficult to differentiate from DHRs. The majority of children are incorrectly labeled as "allergic." Therefore, allergy to BLs in children is overdiagnosed. These children often receive suboptimal treatment with second-line broad-spectrum antibiotics, which are less effective, more costly, and associated with an increased risk of antibiotic-resistant infections. This prolongs hospitalization and thus more uses health care. The correct diagnosis of BL allergy in children is still an important and hot topic. This review has outlined the need for correct diagnosis of BL allergy in children and all the controversies encountered by pediatricians and pediatric allergists. It is also necessary to change the paradigm.

Coronavirus disease 2019 (COVID‐19), a respiratory tract infection caused by a novel human coronavirus, the severe acute respiratory syndrome coronavirus 2, leads to a wide spectrum of clinical manifestations ranging from asymptomatic cases to patients with mild and severe symptoms, with or without pneumonia. Given the huge influence caused by the overwhelming COVID‐19 pandemic affecting over three million people worldwide, a wide spectrum of drugs is considered for the treatment in the concept of repurposing and off‐label use. There is no knowledge about the diagnosis and clinical management of the drug hypersensitivity reactions that can potentially occur during the disease. This review brings togetherall the published information about the diagnosis and management of drug hypersensitivity reactions due to current and candidate off‐label drugs andhighlights relevant recommendations. Furthermore, it gathers all the dermatologic manifestations reported during the disease for guiding the clinicians to establish a better differential diagnosis of drug hypersensitivity reactionsin the course of the disease.

Immune modulation is a key therapeutic tool for allergic diseases and asthma. It can be achieved in an antigen-specific way via allergen immunotherapy (AIT) or in endotype-driven approach using biologicals that target the major pathways of the type 2 (T2) immune response: IgE, IL-5 and IL-4/IL-13. COVID-19 vaccine provides an excellent opportunity to tackle the global pandemics and is currently being applied in an accelerated rhythm worldwide. It works as well through immune modulation. Thus, as there is an obvious interference between these treatment modalities recommendations on how they should be applied in sequence are expected. The European Academy of Allergy and Clinical Immunology (EAACI) gathered an outstanding expert panel under its Research and Outreach Committee (ROC). This expert panel was called to evaluate the evidence and formulate recommendation on the administration of COVID-19 vaccine in patients with allergic diseases and asthma receiving AIT or biologicals. The panel also formulated recommendations for COVID-19 vaccine in association with biologicals targeting the type 1 or type 3 immune response. In formulating recommendations, the panel evaluated the mechanisms of COVID-19 infection, of COVID-19 vaccine, of AIT and of biologicals and considered the data published for other anti-infectious vaccines administered concurrently with AIT or biologicals.

The objective of the paper is to investigate whether probiotic supplementation prenatally and/or postnatally could prevent the development of atopic/allergic march after systematically reviewed the literature. The atopic march refers to the natural history of allergic diseases which develop during infancy and childhood. Allergic diseases, including atopic dermatitis, IgE-mediated food allergy, asthma, and allergic rhinitis, have dramatically increased over the last century. It is now known that every fourth child is allergic, but assumed that in 2020 every second child will be allergic. Pub Med were searched for randomized controlled trials regarding the effect of probiotics on the prevention of allergy in children. Type 2 inflammation is the central tenet of the atopic march. Intestinal microflora play an important role in the Th1/Th2 balance. Probiotics are cultures of potentially beneficial bacteria that positively affect the host by enhancing the microbial balance and they restore the normal intestinal permeability and gut microecology. Therefore, the use of probiotics prenatally and postnatally may counterbalance the Th2 immune phenotype, thus preventing the development of the atopic march. Probiotics administration is able to reduce atopic inflammation and to enhance anti-inflammatory markers. Conclusion – The current systemic review suggests that probiotics administered prenatally and postnatally could reduce the risk of atopy and food allergy in young children, but they are not helpful in the prevention of asthma.

Objectives: The aim of this study was to assess the epidemiological, clinical, endoscopic, and pathohistological characteristics of pediatric eosinophilic esophagitis (EoE) in Serbia. Method: All children aged 0–18 years diagnosed with EoE in the period between 2010 and 2017 at the University Children’s Hospital in Belgrade, Serbia, were retrospectively enrolled. Results: EoE was diagnosed in 35 children (12.45 ± 3.77 years) with a male predominance (74%). The median incidence rate was estimated to be 0.85 per 100,000 children per year with the highest rate estimated at 3.17 per 100,000 children in 2017. Dysphagia (71.4%) and food impaction (40%) were dominant symptoms. Inflammatory endoscopic changes were found in 74.3% and fibrostenotic changes in 62.9% of the children. The esophageal biopsy rate was low (6.8%), especially in children with reflux and nonspecific symptoms. Subepithelial fibrosis was found in only 20% of the patients. Since 2016, the number of biopsy samples has increased, but the sampling rate of lamina propria is still low (rs = 0.773, p < 0.05). In 2 immunocompetent adolescents, EoE was diagnosed after successful treatment of infectious esophagitis. Conclusions: An increase in the incidence of EoE in Serbian children is evident. The biopsy rate in children with nonspecific and reflux symptoms should be increased, as well as the number of biopsy samples for the detection of subepithelial fibrosis. In immunocompetent children with infectious esophagitis, EoE should be suspected and endoscopy may be recommended after successful treatment of infection.

Purpose of review The true exanthematous reactions to drugs in children are rare and overdiagnosed. Drugs may cause exanthema either due to inducing an immune response or because of their interaction with viruses, if drugs are taken in the course of a viral infection. Also, viral infections are very often in children and they can provoke an exanthema which is difficult to differentiate from exanthematous reactions to drugs. Consequently, the majority of children are incorrectly labeled as 'allergic'. Recent findings The correct diagnosis of exanthematous drug reactions in children is still an important and hot topic. Most information about the approach and management of drug hypersensitivity in children is applied from available guidelines and consensus statement for adults. Recently, a systematic clinical approach for timely differential diagnosis and management of rashes in children who present a cutaneous exanthema while receiving a drug, is proposed. Summary It is important to consider the detailed clinical history of appearing and developing exanthematous drug reaction, as well as physical examination which includes the description and the distribution of exanthema and at the end making the appropriate diagnosis. Thus, it could reduce overdiagnosis and promote appropriate procedures, that will prevent the overlabeling of drug hypersensitivity in children.

Beta-lactam (BL) allergy suspicion is common in children and constitutes a major public health problem, with an impact on patient's health and on medical costs. However, it has been found that most of these reactions are not confirmed by a complete allergic workup. The diagnostic value of the currently available allergy tests has been investigated intensively recently by different groups throughout the world. This has led to major changes in the management of children with a suspected BL allergy. Particularly, it is now well accepted that skin tests can be skipped before the drug provocation test in children with a benign non-immediate reaction to BL. However, there is still a debate on the optimal allergic workup to perform in children with a benign immediate reaction. In addition, management of children with severe cutaneous adverse drug reactions remains difficult. In this review, based on a selection of the most relevant studies found in the literature, we will review and discuss the diagnosis of different forms of BL allergy in children.

International audience; Background: Antiepileptic drugs (AEDs) are widely used for the treatment of epilepsy, but they can be associated with the development of mainly delayed/non-immediate hypersensitivity reactions (HRs). Although these reactions are usually cutaneous, self-limited, and spontaneously resolve within days after drug discontinuation, sometime HR reactions to AEDs can be severe and life-threatening.Aim: This paper seeks to show examples on practical management of AED HRs in children starting from a review of what it is already known in literature.Results: Risk factors include age, history of previous AEDs reactions, viral infections, concomitant medications, and genetic factors. The diagnostic workup consists of in vivo (intradermal testing and patch testing) and in vitro tests [serological investigation to exclude the role of viral infection, lymphocyte transformation test (LTT), cytokine detection in ELISpot assays, and granulysin (Grl) in flow cytometry. Treatment is based on a prompt drug discontinuation and mainly on the use of glucocorticoids.Conclusion: Dealing with AED HRs is challenging. The primary goal in the diagnosis and management of HRs to AEDs should be trying to accurately identify the causal trigger and simultaneously identify a safe and effective alternative anticonvulsant. There is therefore an ongoing need to improve our knowledge of HS reactions due to AED medications and in particular to improve our diagnostic capabilities.

Allergen-specific immunotherapy (AIT) is a desensitizing treatment for allergic diseases that corrects the underlined pathological immune response to innocuous protein antigens, called allergens. Recombinant allergens employed in the AIT allowed the production of well-defined formulations that possessed consistent quality but were often less efficient than natural allergen extracts. Combining recombinant allergens with an adjuvant or immunomodulatory agent could improve AIT efficacy. This study aimed to perform structural and functional characterization of newly designed recombinant chimera composed of the Bet v 1, the major birch pollen allergen, and Banana Lectin (BanLec), TLR2, and CD14 binding protein, for the application in AIT. rBet v 1-BanLec chimera was designed in silico and expressed as a soluble fraction in Escherichia coli. Purified rBet v 1-BanLec (33.4 kDa) retained BanLec-associated biological activity of carbohydrate-binding and preserved IgE reactive epitopes of Bet v 1. The chimera revealed secondary structures with predominant β sheets. The immunomodulatory capacity of rBet v 1-BanLec tested on macrophages showed changes in myeloperoxidase activity, reduced NO production, and significant alterations in the production of cytokines when compared to both rBanLec and rBet v 1. Comparing to rBet v 1, rBet v 1-BanLec was demonstrated to be more efficient promoter of IL-10 production as well as weaker inducer of NO production and secretion of pro-inflammatory cytokines TNFα, and IL-6. The ability of rBet v 1-BanLec to promote IL-10 in together with the preserved 3D structure of Bet v 1 part implies that the construct might exert a beneficial effect in the allergen-specific immunotherapy.

The aim of this study was to identify short digestion-resistant peptides (SDRPs) released by pepsin digestion of the whole cow’s milk and examine their IgE reactivity and allergenicity. Raw milk was subjected to simulated gastric digestion. SDRPs were fractionated from the digests and identified by MS. Milk SDRPs were evaluated for aggregability, propensity to compete for IgE binding with individual milk allergens, and ability to bind IgG4 from allergic and milk-tolerant individuals. The majority of milk SDRPs originated from caseins (97% of peptides) and overlapped with the known IgE epitopes of cow’s milk allergens. SDRPs competed with milk proteins for binding to human IgE and readily formed aggregates. The average peptide length was 10.6 ± 3.5 amino acids. The ability to provoke allergenic in vivo responses was confirmed by skin-prick testing (SPT) in five milk-allergic subjects. This was attributed to the peptide ability to aggregate into non-covalent complexes. SDRPs are able to induce response in SPT, but only in 50% of the sera SDRPs were able to inhibit IgG4 binding to caseins. Hence, SDRPs corresponding to the mainly continuous epitopes of milk proteins induce allergenic in vivo responses in milk-allergic subjects due to aggregation.

This review highlights the novelties in understanding the underlying immunological mechanisms of drug hypersensitivity reactions (DHRs) as well as tiny changes in clinical classification and diagnosis of DHRs with special reference to beta-lactams (BLs) in the pediatric population, in the last couple of years. Viral infections are very often in children and they can provoke skin rashes which is difficult to differentiate from DHRs. Because of that allergy to BLs in children is overdiagnosed. The correct diagnosis of BLs allergy in children is still an important and hot topic. In this review has been outlined the need for correct diagnosis of BLs allergy in children as well as needed to change the paradigm.

International audience; Coronavirus disease 2019 (COVID-19), a respiratory tract infection caused by a novel human coronavirus, the severe acute respiratory syndrome coronavirus 2, leads to a wide spectrum of clinical manifestations ranging from asymptomatic cases to patients with mild and severe symptoms, with or without pneumonia. Given the huge influence caused by the overwhelming COVID-19 pandemic affecting over three million people worldwide, a wide spectrum of drugs is considered for the treatment in the concept of repurposing and off-label use. There is no knowledge about the diagnosis and clinical management of the drug hypersensitivity reactions that can potentially occur during the disease. This review brings together all the published information about the diagnosis and management of drug hypersensitivity reactions due to current and candidate off-label drugs and highlights relevant recommendations. Furthermore, it gathers all the dermatologic manifestations reported during the disease for guiding the clinicians to establish a better differential diagnosis of drug hypersensitivity reactions in the course of the disease.

International audience; Drug hypersensitivity reactions (DHRs) are associated with high global morbidity and mortality. Cutaneous T cell-mediated reactions classically occur more than 6 hours after drug administration and include life-threatening conditions such as toxic epidermal necrolysis, Stevens-Johnson syndrome, and hypersensitivity syndrome. Over the last 20 years, significant advances have been made in our understanding of the pathogenesis of DHRs with the identification of human leukocyte antigens as predisposing factors. This has led to the development of pharmacogenetic screening tests, such as HLA-B*57:01 in abacavir therapy, which has successfully reduced the incidence of abacavir hypersensitivity reactions. We have completed a PRISMA-compliant systematic review to identify genetic associations that have been reported in DHRs. In total, 105 studies (5554 cases and 123 548 controls) have been included in the review reporting genetic associations with carbamazepine (n = 31), other aromatic antiepileptic drugs (n = 24), abacavir (n = 11), nevirapine (n = 14), trimethoprim-sulfamethoxazole (n = 11), dapsone (n = 4), allopurinol (n = 10), and other drugs (n = 5). The most commonly reported genetic variants associated with DHRs are located in human leukocyte antigen genes and genes involved in drug metabolism pathways. Increasing our understanding of genetic variants that contribute to DHRs will allow us to improve diagnosis, develop new treatments, and predict and prevent DHRs in the future.

Oteros, Jose/0000-0002-9369-8633; Fonseca, Joao Almeida/0000-0002-0887-8796; Alvarez-Perea, Alberto/0000-0001-7417-7309; Oteros, Jose/0000-0002-9369-8633; Gevaert, Philippe/0000-0002-1629-8468; Antolin, Dario/0000-0001-5699-4022; Apfelbacher, Christian/0000-0003-3805-8219; Buters, Jeroen/0000-0003-3581-5472; Berger, Uwe E./0000-0002-9265-2131; Blank, Simon/0000-0002-5649-1078; Cardona, Victoria/0000-0003-2197-9767; Dramburg, Stephanie/0000-0002-9303-3260 WOS: 000486665800001 PubMed: 31230373 Mobile health (mHealth) uses mobile communication devices such as smartphones and tablet computers to support and improve health-related services, data and information flow, patient self-management, surveillance, and disease management from the moment of first diagnosis to an optimized treatment. The European Academy of Allergy and Clinical Immunology created a task force to assess the state of the art and future potential of mHealth in allergology. The task force endorsed the "Be He@lthy, Be Mobile" WHO initiative and debated the quality, usability, efficiency, advantages, limitations, and risks of mobile solutions for allergic diseases. The results are summarized in this position paper, analyzing also the regulatory background with regard to the "General Data Protection Regulation" and Medical Directives of the European Community. The task force assessed the design, user engagement, content, potential of inducing behavioral change, credibility/accountability, and privacy policies of mHealth products. The perspectives of healthcare professionals and allergic patients are discussed, underlining the need of thorough investigation for an effective design of mHealth technologies as auxiliary tools to improve quality of care. Within the context of precision medicine, these could facilitate the change in perspective from clinician- to patient-centered care. The current and future potential of mHealth is then examined for specific areas of allergology, including allergic rhinitis, aerobiology, allergen immunotherapy, asthma, dermatological diseases, food allergies, anaphylaxis, insect venom, and drug allergy. The impact of mobile technologies and associated big data sets are outlined. Facts and recommendations for future mHealth initiatives within EAACI are listed.

Introduction. Empyema thoracis, defined as the accumulation of pus in the pleural space, is rare in neonatal population. There are limited data reported in the medical literature and there are still no treatment guidelines available for this age. Case report. We present a healthy term 12-day-old neonate with sepsis caused by methicillin-resistant Staphylococcus aureus (MRSA) and pneumonia associated with advanced stage empyema. The child was admitted to our hospital with a few-hours history of difficulty breathing and lethargy. At the admission, the child was cyanotic with desaturation, in severe respiratory distress, so it was intubated and started mechanical ventilation. Imaging tests were performed in emergency, therefore chest computed tomography (CT) scan was done without contrast. Suspected congenital pulmonary airway malformation (CPAM) with trapped air collections, significant mediastinal shift on CT scan and deterioration of the patient?s condition indicated urgent surgery. Intraoperatively, the diagnosis of stage 2 empyema was established, and decortication of thickened parietal and visceral pleura was performed. Afterwards the baby showed quick and progressive clinical improvement. Conclusion. The diagnosis and management of empyema in neonates may be a challenging one, especially in the case of unremarkably history, fulminant and rapid progression of the disease and incomplete imaging tests.

The tendency to develop multiple drug hypersensitivity (MDH), defined as a hypersensitivity to two or more structurally unrelated drugs, occurs in up to 10% of people who have a severe and proven immune-mediated drug hypersensitivity reaction (DHR). There are two subtypes of MDH: in the first type, MDH develops if different drugs are administered simultaneously; in the second, MDH develops if different drugs are administered sequentially, sometimes years apart. MDH presents clinically as immediate and/or non-immediate reactions. The main drugs responsible for MDH are antibiotics, non-steroidal anti-inflammatory drugs (NSAIDs), antiepileptics, hypnotics, antidepressants, corticosteroids, and local anesthetics. There are two pathogenic mechanisms of developing MDH: the first is T cell mediated and the second is IgE mediated. Activated T cells are directed against the culprit drug or its metabolites. MDH can be proven by positive responses to patch tests and/or delayed-reading intradermal tests as well as a positive lymphocyte transformation test. During the first DHR, the immune stimulation may lower the threshold of T cell reactivity to that drug and facilitate the immune response to the second drug, similar to viral infections. The drug-reactive T cells in patients with MDH display an enhanced state of activation. Less frequently, the pathogenic mechanism is IgE mediated. This can be proven by positive responses to an immediate-reading intradermal test and provocation test, as well as with positive specific IgE to culprit drug and a basophil activation test (BAT). A T cell-mediated reaction might be built on the IgE-mediated reaction. It is well-known that the tolerance mechanism to small molecular compounds fails in MDH patients, although the pathogenic mechanisms of this syndrome are still unknown.

International audience; A recent survey of the European Academy of Allergy and Clinical Immunology (EAACI) Drug Allergy Interest Group (DAIG) on how European allergy specialists deal with beta-lactam (BL) hypersensitivity demonstrated a significant heterogeneity in current practice, suggesting the need to review and update existing EAACI guidelines in order to make the diagnostic procedures as safe and accurate, but also as cost-effective, as possible. For this purpose, a bibliographic search on large studies regarding BL hypersensitivity diagnosis was performed by an EAACI task force, which reviewed and evaluated the literature data using the GRADE system for quality of evidence and strength of recommendation. The updated guidelines provide a risk stratification in BL hypersensitivity according to index reaction(s), as well as an algorithmic approach, based on cross-reactivity studies, in patients with a suspicion of BL hypersensitivity and an immediate need for antibiotic therapy, when referral to an allergist is not feasible. Furthermore, the update addresses availability and concentrations of skin test (ST) reagents, ST and drug provocation test (DPT) protocols, as well as diagnostic algorithms and administration of alternative BL in allergic subjects. Specifically, distinct diagnostic algorithms are suggested depending on risk stratification of the patient into high and low risk based on the morphology and chronology of the reaction, immediate (i.e., occurring within 1 to 6 hours after the last administered dose) or nonimmediate (i.e., occurring more than 1 hour after the initial drug administration), and the reaction severity. Regarding the allergy workup, the main novelty of this document is the fact that in some low-risk nonimmediate reactions ST are not mandatory, especially in children. For DPT, further studies are necessary to provide data supporting the standardization of protocols, especially of those regarding nonimmediate reactions, for which there is currently no consensus.

International audience; An accurate diagnosis of β‐lactam (BL) allergy can reduce patient morbidity and mortality. Our aim was to investigate the availability of BL reagents, their use and test procedures in different parts of Europe, as well as any differences in the diagnostic workups for evaluating subjects with BL hypersensitivity. A survey was emailed to all members of the EAACI Drug Allergy Interest Group (DAIG) between February and April 2016, and the questionnaire was meant to study the management of suspected BL hypersensitivity. The questionnaire was emailed to 82 DAIG centres and answered by 57. Amoxicillin alone or combined to clavulanic acid were the most commonly involved BL except in the Danish centre, where penicillin V was the most frequently suspected BL. All centres performed an allergy workup in subjects with histories of hypersensitivity to BL: 53 centres (93%) followed DAIG guidelines, two national guidelines and two local guidelines. However, there were deviations from DAIG recommendations concerning allergy tests, especially drug provocation tests. A significant heterogeneity exists in current practice not only among countries, but also among centres within the same country. This suggests the need to re‐evaluate, update and standardize protocols on the management of patients with suspected BL allergy.

Background Diagnosis of hypersensitivity (HS) reactions to nonsteroidal anti-inflammatory drugs (NSAIDs) in children is complex. The real prevalence of NSAID HS remains unknown because a drug provocation test (DPT) is not always performed with the culprit NSAID. Objective To describe and compare the diagnostic workup among different European centers and to find out the real proportion of NSAID HS by performing a DPT with the culprit drug. Methods We retrospectively collected data from children (0-10 years) and adolescents (10-18 years) with a history of NSAID reactions and who underwent a complete allergy workup including DPTs with the culprit in 6 different pediatric centers: Belgrade, Florence, Geneva, Madrid, Porto, and Rome. Results A total of 693 children with a history of NSAID reactions were enrolled, and a total of 526 DPTs were performed with the culprit NSAID. The diagnosis of NSAID HS was confirmed in 19.6% (103 of 526) of children by performing a DPT with the culprit drug. The major differences in the allergy workup among the 6 centers concerned the duration of the DPT and the practical use of skin tests for diagnosing NSAID HS. In addition, the use of acetyl salicylic acid to differentiate single reactor or cross-intolerance patients is not common, except in Spain. Conclusion The value of this study is that although different approaches are used around Europe to diagnose NSAID HS, we found that the percentage of confirmed NSAID HS is less than 20%. This highlights the importance of the DPT in confirming or excluding NSAID HS in the pediatric population.

Background Antiepileptic drugs (AEDs) can cause hypersensitivity reactions in children. These reactions are mainly cutaneous, self-limiting, and benign, but life-threatening severe cutaneous adverse reactions can occur. Infections can lead to skin eruptions and mimic drug hypersensitivity reactions, if a drug is taken at the same time. The aims of our study were to confirm or rule out the diagnosis of hypersensitivity reactions to AEDs in children and to detect an infection which mimics these reactions. Methods A prospective survey was conducted in a group of 100 children with histories of hypersensitivity reactions to AEDs by performing patch tests, delayed-reading intradermal test, and, in case of negative results, challenge test. In all children, a study was performed to detect infections by viruses or Mycoplasma pneumoniae. Results Maculopapular exanthema and delayed-appearing urticaria were the most reported hypersensitivity reactions to AEDs. Sixty-six (66%) of 100 children had confirmed hypersensitivity reactions to AEDs. Fifty-nine children had positive patch test. No children had positive challenge tests. The most common AEDs causing hypersensitivity reactions were carbamazepine (45.4%) and lamotrigine (43.6%). Thirty-two children had positive tests for viruses or M pneumoniae, and nine of them had also a positive allergy work-up. Conclusion Considering that there are no specific tests to distinguish between a viral infection and hypersensitivity reactions to AEDs in the acute phase, a diagnostic work-up should be performed in all children with suspected hypersensitivity reactions to AEDs, as well as infectious agent study, to remove a false label of hypersensitivity.

BACKGROUND Group 1 and group 2 allergens from house dust mite are the major elicitors of respiratory allergic diseases and the main candidates for immunotherapy. RESULTS The potential therapeutic role of a chimera composed of recombinant Der p 2 (D2) linked to Influenza A virus hemagglutinin 1 (H1) for intranasal application was created, expressed and tested in a mouse model. H1D2 and D2 were produced by genetic engineering in E. coli and their primary structure was confirmed by mass fingerprint. Both antigens preserved IgE reactivity in immunoblot with serum from seven house dust mite allergic persons. Balb/c mice were sensitized with D2 allergen in alum and subsequently received H1D2 or D2, intranasally. The reduced levels of serum D2 specific IgE, together with the increased serum specific IgG and IgA were detected in both groups which received H1D2 and D2 intranasally. A higher level of effector CD4+CD25+ spleen lymphocytes was found only in the group of mice which received i.n. H1D2. CONCLUSION H1D2 chimera can have a therapeutic potential in Der p 2 allergic persons as dual vaccine which, beside protective allergen specific, can provide protective antibodies against Influenza A virus hemagglutinin 1.

The strongest and best-documented risk factor for drug hypersensitivity (DH) is the history of a previous reaction. Accidental exposures to drugs may lead to severe or even fatal reactions in sensitized patients. Preventable prescription errors are common. They are often due to inadequate medical history or poor risk assessment of recurrence of drug reaction. Proper documentation is essential information for the doctor to make sound therapeutic decision. The European Network on Drug Allergy and Drug Allergy Interest Group of the European Academy of Allergy and Clinical Immunology have formed a task force and developed a drug allergy passport as well as general guidelines of drug allergy documentation. A drug allergy passport, a drug allergy alert card, a certificate, and a discharge letter after medical evaluation are adequate means to document DH in a patient. They are to be handed to the patient who is advised to carry the documentation at all times especially when away from home. A drug allergy passport should at least contain information on the culprit drug(s) including international nonproprietary name, clinical manifestations including severity, diagnostic measures, potential cross-reactivity, alternative drugs to prescribe, and where more detailed information can be obtained from the issuer. It should be given to patients only after full allergy workup. In the future, electronic prescription systems with alert functions will become more common and should include the same information as in paper-based documentation.

Drug hypersensitivity reactions (DHR) constitute a major and common public health problem, particularly in children. One of the most severe manifestations of DHR is anaphylaxis, which might be associated with a life-threatening risk. During those past decades, anaphylaxis has received particularly a lot of attention and international consensus guidelines have been recently published. Whilst drug-induced anaphylaxis is more commonly reported in adulthood, less is known about the role of drugs in pediatric anaphylaxis. Betalactam antibiotics and non-steroidal anti-inflammatory drugs are the most commonly involved drugs, probably related to high prescription rates. Diagnosis relies on the recognition of symptoms pattern and is based on complete allergic workup, particularly including skin tests and/or specific IgE. However, the real diagnostic value of those tests to diagnose immediate reactions in children remains not well defined for a significant number of the drugs. Generally, a drug provocation test is discussed to confirm or exclude an immediate-onset drug-induced hypersensitivity. Although avoidance of the incriminated drug (and related drug) is the rule, rapid desensitization is useful in selected subgroups of patients. There is a need for large, multicentric studies, to evaluate the real diagnostic value of the currently available skin tests. Moreover there is also a need to develop new diagnostic tests in the future to improve the management of these children.

Despite their low frequency, drug hypersensitivity reactions (DHRs) can be serious and result in lifelong sequelae. The diagnosis is critical to avert future reactions and should identify the culprit drug or drugs and safe alternatives. However, making the diagnosis can be complex and challenging. Reliable in vitro tests can offer the potential to improve a diagnosis of DHR and influence medical decision making. Importantly, in vitro testing is frequently not performed as a test in isolation but rather as a component of a diagnostic algorithm along with additional tests. There are several in vitro approaches for the different endotypes of DHRs. However, only few are available for routine diagnosis, and many are restricted to research laboratories. In vitro tests exhibit varying sensitivity and specificity depending on the drug involved and the clinical phenotype. In vitro tests can complement skin tests, especially in patients with negative or equivocal skin test responses inconsistent with the clinical presentation and in severe reactions in which drug provocation tests are contraindicated. The main unmet need for many in vitro tests for the diagnosis of DHRs is validation in larger studies with standardized controls that could harmonize diagnostic management between the United States, European Union, and other regions of the world.

The history of pediatric allergology (PA) in Europe is relatively youthful, dating back to 1984, when a small group of pediatricians founded the European Working Group on Pediatric Allergy and Immunology-later giving rise to ESPACI (European Society on Pediatric Allergology and Clinical Immunology). In 1990, the first dedicated journal, Pediatric Allergy and Immunology (PAI), was founded. There are striking differences across Europe, and even within European countries, in relation to the training pathways for doctors seeing children with allergic disease(s). In 2016, the EAACIClemens von Pirquet Foundation (CvP) organized and sponsored a workshop with the European Academy of Allergy and Clinical Immunology (EAACI) Pediatric Section. This collaboration focussed on the future of PA and specifically on education, research, and networking/ advocacy. The delegates representing many countries across Europe have endorsed the concept that optimal care of children with allergic diseases is delivered by pediatricians who have received dedicated training in allergy, or allergists who have received dedicated training in pediatrics. In order to meet the needs of children and families with allergic disease(s), the pediatric allergist is highly encouraged to develop several networks. Our challenge is to reinforce a clear strategic approach to scientific excellence to across our member base and to ensure and enhance the relevance of European pediatric research in allergy. With research opportunities in basic, translational, clinical, and epidemiologic trials, more trainees and trained specialists are needed and it is an exciting time to be a pediatric allergologist.

Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used in the pediatric population as antipyretics/analgesics and anti-inflammatory medications. Hypersensitivity (HS) reactions to NSAID in this age group, while similar to adults, have unique diagnostic and management issues. Although slowly accumulating, published data in this age group are still relatively rare and lacking a unifying consensus. This work is a summary of current knowledge and consensus recommendations utilizing both published data and expert opinion from the European Network of Drug Allergy (ENDA) and the Drug Hypersensitivity interest group in the European Academy of Allergy and Clinical Immunology (EAACI). This position paper summarizes diagnostic and management guidelines for children and adolescents with NSAIDs hypersensitivity.

Polyphenols, the potent plant secondary metabolites, have beneficial effects on human health, but the mechanism(s) by which these effects are exerted is not well understood. Here, we present the detailed analysis of the interactions between the major green tea catechin, epigallo-catechin 3-gallate (EGCG), and the major dietary protein and allergen, ovalbumin (OVA). We show that EGCG binds to the pocket that partly overlaps with the previously identified IgE-binding region in OVA, and that this interaction induces structural changes in the allergen. Moreover, our ex vivo studies reveal that OVA binds IgE and stimulates degranulation of basophils, and that its uptake by monocytes proceeds at a slower rate in the presence of EGCG. This study provides further evidence in support of the proposed mechanism by which EGCG interactions with the food allergens contribute to its diverse biological activities and may impair antigen uptake by antigen-presenting cells. (C) 2014 Elsevier Ltd. All rights reserved.

ackground: Protein oxidation can occur as a consequence of lipid peroxidation during food processing. The aim of this work was to explore the effect of malondialdehyde (MDA) modification of ovalbumin (OVA) on its interaction with T84 intestinal cells. Methods: Molecular dynamics simulation was employed for the prediction of MDA modification in the OVA, while introduced structural changes were evaluated by measurement of carbonyl group content, fluorescence spectra, MS/MS analysis, and IgE reactivity. Effects of MDA modified OVA on T84 epithelial cells were analyzed by gene expression for pro-inflammatory cytokines and protein secretion. Results: Out of 9 predicted, five modified Lys residues were confirmed by MS/MS analysis: (51)TQINKVVR(58), (85)DILNQITKPNDVYSFSLASR(104), (111)YPILPEYLQCVKELYR(126), (187)AFKDEDTQAMPFR(99), (KIKVYLPR284)-K-277, and (IKVYLPR284)-I-278. The introduced MDA modifications influenced profile of IgE reactivity to OVA. Treatment of T84 epithelial cells with OVA and OVA modified with 1 mM MDA, induced up-regulation of pro-inflammatory cytokines (IL-1 beta,IL-25, IL-33, TSLP and TNF alpha), while OVA modification with 10 mM MDA induced down regulation of the cytokine expression profile, except for IL-1 beta. OVA and OVA modified with 1 mM MDA induced secretion of epithelial cells specific cytokine IL-33. Conclusions: This finding indicated that OVA and its MDA modified form have the potential to trigger the innate immunity by inducing up-regulation and secretion of pro-allergenic IL-33 in T84 intestinal epithelial cells. General significance: Interactions of ovalbumin and its MDA modified form with intestinal epithelial cells can induce a specific immunological priming necessary for the downstream activation of innate immunity. (C) 2016 Elsevier B.V. All rights reserved. This is the peer-reviewed version of the following article:Nikolic, J.; Nešić, A. N.; Cavic, M.; Dordevic, N.; Andelkovic, U.; Atanaskovic-Markovic, M.; Drakulić, B. J.; Gavrović-Jankulović, M. Effect of Malondialdehyde on the Ovalbumin Structure and Its Interactions with T84 Epithelial Cells. Biochimica et Biophysica Acta: General Subjects 2017, 1861 (2), 126–134. [https://doi.org/10.1016/j.bbagen.2016.11.021]

The arm of this review was to help general pediatricians and primary care physicians in diagnosing and managing cow's milk protein allergy in exclusively breast-fed infants. Allergic proctocolitis is a cause of rectal bleeding in exclusively breast-fed infants aged from 1 to 6 months.It is due to cow's milk protein transferred via breast milk. Diagnosis is based on clinical features and recovery after dietetic therapy. Rectal bleeding generally resolves within 72-96 hours of cow's milk protein maternal avoidance. Most infants tolerate cow's milk by their first birthday.

Background The role of pet exposure in childhood asthma and allergy is still controversial. The aim of this study was to investigate the association between pet-keeping during different periods of childhood and asthma and sensitization in school children. Methods One hundred and forty-nine children aged between 7 and 14 years were enrolled in this study. Seventy-four children had current physician-diagnosed asthma, while 75 children did not have asthma. Pet-keeping was investigated by questionnaire. Allergic sensitization to pet allergen was assessed on skin prick tests and specific serum IgE concentration. Logistic regression analysis was performed, taking into account potential confounders. Results Early, past and current pet-keeping was not significantly associated with asthma. Neither owning a cat nor dog during childhood was associated with asthma. Early pet-keeping, however, was significantly associated with sensitization to pet allergens (adjusted odds ratio [aOR], 24.11; 95% confidence interval [CI]: 3.28–177.27). Further analysis showed that only early cat-keeping was significantly associated with sensitization to cat allergen (aOR, 51.59; 95%CI: 2.28–1167.07). Keeping a cat or a dog after the first year of life was not associated with sensitization to those allergens. Conclusions Keeping a cat or a dog does not increase risk for asthma. Keeping a cat in the first year of life, however, increases risk of sensitization to cat allergen. Considering that this is a relatively small study, larger, prospective, birth cohort studies are required in Serbia to accurately assess the relationship between pet-keeping, asthma and sensitization.

Allergic diseases are common in childhood and can cause a significant morbidity and impaired quality-of-life of the children and their families. Adequate allergy testing is the prerequisite for optimal care, including allergen avoidance, pharmacotherapy and immunotherapy. Children with persisting or recurrent or severe symptoms suggestive for allergy should undergo an appropriate diagnostic work-up, irrespective of their age. Adequate allergy testing may also allow defining allergic trigger in common symptoms. We provide here evidence-based guidance on when and how to test for allergy in children based on common presenting symptoms suggestive of allergic diseases.

Background: Non-immediate reactions to beta-lactam antibiotics (BL) occur more than one hour after drug administration, and the most common manifestations are maculopapular exanthemas and delayed-appearing urticaria and/or angioedema. Infections can lead to skin eruptions and mimic drug hypersensitivity reactions (DHR), if a drug is taken at the same time. The most of children are labeled as drug allergic' after considering only the clinical history. Objective: To diagnose/detect a hypersensitivity or an infection which mimic DHR in children with non-immediate reactions to BL Methods: A prospective survey was conducted in a group of 1026 children with histories of non-immediate reactions to BL by performing patch tests, skin tests, and in case of negative results, drug provocation tests (DPTs). In 300 children, a study was performed to detect infections by viruses or Mycoplasma pneumoniae. Results: Urticaria and maculopapular exanthemas were the most reported non-immediate reactions. Only 76 (7.4%) of 1026 children had confirmed non-immediate hypersensitivity reactions to BL. Fifty-seven children had positive delayed-reading intradermal tests (18 of these with a positive patch test). Nineteen children had positive DPT. Sixty-six of 300 children had positive tests for viruses or Mycoplasma pneumoniae and 2 of them had a positive allergy work-up. Conclusions: A diagnostic work-up should be performed in all children with non-immediate reactions to BL, to remove a false label of hypersensitivity. Even though only 57 (5.5%) of 1026 children displayed positive responses to delayed-reading intradermal tests to BL, such tests appear to be useful in order to reduce the risk for positive DPTs.

Modified allergens are a safer and more efficient alternative to natural allergens for specific immunotherapy. As the modification of an allergen can diminish its immunogenicity due to the alteration of T-cell epitopes, in this paper we study the effects of a reversible chemical modification of Art v 1, the main allergen of mugwort pollen, on its allergenicity and immunogenicity. Modification of Art v 1 by cis-aconitylation into a polyanionic derivative (CAA) did not result in any significant structural alteration. However, IgE-binding epitopes on CAA were blocked, resulting in a reduced IgE-binding and basophil activation. Both proteins induced proliferation of CD3(+)CD4(+) T-cells in mugwort-allergic patients, but only unmodified allergens increased IL-4, IL-5 and IL-10 production. Rabbit and mouse anti-CAA antibodies exhibited cross-reactivity with native allergens and blocked human IgE-binding to Art v 1. Degradation of CAA by lysosomal fraction enzymes resulted in a similar set of peptides, harboring MHC class II-binding peptides, as unmodified proteins. Thus, cis-aconitylation modified Art v 1 had a significantly reduced allergenicity, whereas its immunogenicity was completely preserved. Acid-environment-responsive modification, which releases a full repertoire of native allergen epitopes within a particular site, can be considered a smart drug delivery system, which is able to deliver a therapeutically-effective dose in a controlled manner, and minimizes adverse side effects. Supplementary material: [http://cherry.chem.bg.ac.rs/handle/123456789/3528]

For the heterologous production of a banana glucanase in Escherichia coli, its gene (GenBank GQ268963) was cloned into a pGEX-4T expression vector as a fusion protein with glutathione-S-transferase (GST). BL21 cells transformed with the GST-Mus a 5 construct were employed for the protein production induced by 1 mM of isopropyl-?-D-tiogalactopyranoside (IPTG). Conditions for the protein expression were optimized by varying the temperature (25?C, 30?C, and 37?C) and duration of protein expression (3h, 6h and 12h). The level of protein production was analyzed by densitometry of sodium dodecyl sulfate - polyacrylamide gel (SDS-PAG) after electrophoretic resolution of respective cell lysates. The optimal protein expression for downstream processing was obtained after 12h of cell growth under 25?C upon addition of IPTG. Recombinant GST-Mus a 5 purified by glutathione affinity chromatography revealed a molecular mass of about 60 kDa. The IgE and IgG reactivity of rGST-Mus a 5 was confirmed by dot blot analysis with individual patient?s sera from subjects with banana allergy and polyclonal rabbit antibodies against banana extract, respectively. Purified recombinant glucanase is a potential candidate for banana allergy diagnosis.

Penicillins and cephalosporins are the most widely used antibiotics for the treatment of common infections, and they are the two main classes of β-lactams. On the basis of the time of appearance of the reaction after drug intake and for diagnostic purposes, hypersensitivity reactions to β-lactams have been classified as immediate or non-immediate. The diagnostic evaluation of allergic reactions to β-lactams has changed over the last decade, for several reasons. In many countries, major and minor determinants for skin testing are not available. In immediate allergic reactions, the sensitivity of skin testing is decreasing. For non-immediate reactions, skin testing appears to be less sensitive than previously reported. The drug provocation test is still necessary for diagnosis. In this education review series, we described three cases of β-lactam allergy: first, a child with an IgE-mediated allergy to benzyl-penicillin; second, a child with a non-allergic hypersensitivity to amoxicillin; and in the third patient, we will discuss about cross-reactivity between penicillins and cephalosporins. These cases are correlated with the practical management of evaluating β-lactam allergy.

Crosslinking enzymes are frequently used in bioprocessing of dairy products. The aim of this study was to examine the effects of enzymatic crosslinking on IgE binding, allergenicity and digestion stability of beta-casein (CN). beta-CN was crosslinked by transglutaminase, tyrosinase, mushroom tyrosinase/caffeic acid and laccase/caffeic acid. The IgE binding to beta-CN was compared in vitro by CAP inhibition assay, ELISA inhibition as well as ex vivo by basophil activation assay. Crosslinked CNs were digested by simulated gastric fluid for 15 and 60 min and obtained digests analyzed for their ability to inhibit IgE binding by CAP inhibition assay and SDS-PAGE. The ability of crosslinked CNs to activate basophils was significantly reduced in seven patients in the case of CN crosslinked by laccase and moderately reduced in the case of tyrosinase/caffeic acid crosslinked CN (in two cow's milk allergy patients tested with different allergen concentrations). The response to various crosslinked CNs differed individually among patients' sera tested by ELISA inhibition assay. The presence of caffeic acid hampered digestion by pepsin, and this effect was most pronounced for the tyrosinase/caffeic acid crosslinked CN. The laccase/caffeic acid and mushroom tyrosinase/caffeic acid had the highest potential in mitigating IgE binding and allergenicity of the beta-CN out of all investigated enzymes. The presence of a small phenolic compound also increased digestion stability of beta-CN.

Nonallergic hypersensitivity and allergic reactions are part of the many different types of adverse drug reactions (ADRs). Databases exist for the collection of ADRs. Spontaneous reporting makes up the core data-generating system of pharmacovigilance, but there is a large under-estimation of allergy/hypersensitivity drug reactions. A specific database is therefore required for drug allergy and hypersensitivity using standard operating procedures (SOPs), as the diagnosis of drug allergy/hypersensitivity is difficult and current pharmacovigilance algorithms are insufficient. Although difficult, the diagnosis of drug allergy/hypersensitivity has been standardized by the European Network for Drug Allergy (ENDA) under the aegis of the European Academy of Allergology and Clinical Immunology and SOPs have been published. Based on ENDA and Global Allergy and Asthma European Network (GA(2)LEN, EU Framework Programme 6) SOPs, a Drug Allergy and Hypersensitivity Database (DAHD((R))) has been established under FileMaker((R)) Pro 9. It is already available online in many different languages and can be accessed using a personal login. GA(2)LEN is a European network of 27 partners (16 countries) and 59 collaborating centres (26 countries), which can coordinate and implement the DAHD across Europe. The GA(2)LEN-ENDA-DAHD platform interacting with a pharmacovigilance network appears to be of great interest for the reporting of allergy/hypersensitivity ADRs in conjunction with other pharmacovigilance instruments.

House dust mites (HDM) represent a major source of allergens, contributing to the increasing incidence of type I hypersensitivity disease worldwide. Over 30 different IgE-binding proteins from the HDM extract were detected. Although group 1 and 2 have been identified as major allergens, due to the safety and efficacy of allergy diagnosis and immunotherapy, there is a need to carefully evaluate the clinical relevance of other allergens present in the HDM extract. In regard to this, a high molecular mass allergen of about 68 kD was purified from the HDM extract using a combination of gel permeation chromatography and reversed-phase chromatography. The IgG and IgE reactivity of the purified protein were preserved during the purification process, as confirmed by Western blot analysis with polyclonal rabbit antibodies and dot blot analysis with a pool of sera from subjects with house dust mite allergy, respectively. In addition, the IgE reactivity was confirmed using ELISA testing with nine patient sera. The biological potency of the 68 kD allergen was confirmed by skin prick testing in five allergic subjects, suggesting that the high molecular mass allergen is a good candidate for component-resolved diagnosis of house dust mite allergy and eventual therapeutic treatment. Grinje iz kućne prašine predstavljaju jedan od glavnih izvora alergena koji su u značajnoj meri doprineli porastu prvog tipa preosetljivosti. Preko 30 IgE-vezujućih proteina iz kućne prašine je detektovano do danas. Alergeni grupe 1 i 2 označeni su kao glavni alergeni kućne prašine. Međutim, da bi se poboljšala sigurnost i efikasnost dijagnoze i terapije alergijskih oboljenja izazvanih grinjama iz kućne prašine, neophodno je odrediti klinički značaj svih alergena iz ovog alergenskog izvora. U ovom radu izolovan je alergen visoke molekulske mase od 68 kD iz ekstrakta kućne prašine kombinovanjem gel-permeacione hromatografije i reversno-fazne hromatografije. IgG i IgE reaktivnost prečišćenog proteina je proverena u 'Western blot'-u i 'dot blot'-u sa poliklonskim zečijim antitelima na ekstrakt kućne prašine i 'pool'-om seruma osoba alergičnih na kućnu prašinu, redom. 64 % pacijenata je pokazalo IgE reaktivnost na prečišćeni protein u ELISA testu. Biološka reaktivnost prečišćenog alergena je potvrđena u kožnim probama na pet pacijenata, ukazujući da je prečišćen alergen dobar kandidat za dijagnozu alergije na kućnu prašinu pojedinačnim komponentama i eventualni terapeutski tretman.

Introduction: According to recent studies the role of allergy in ethipathogenesis of secretory otitis media is the leading one.The incidence of allergy in secretory otitis media varies from 57% to 100% according to recent studies.The allergic inflammation of the middle aer mucosa is of Th 2 type inflammation of respiratory mucosa.Increased number of activated mast cells, mastocyte tryptase, eosinophyllic cationic protein and mRNA for IL 5 were found in mucosa and effusion in SOM. The aim of this sudy was to investigate the presence of allergies in children with secertory otitis media and to follow up the outcome after antoallergic therapy. Patients and Methods: In this study 71 children with SOM entered the diagnostic procedure for allergy tests. Clinical examination by alergologist, skin prick test, sIgE, eosinophils in nasal lavage were performed.Allergy management was introduced in group of 38 (54%) children with diagnosis of allergy and secretory otitis media. Antihistamines, intranasal cortocosteroids, and elimination of identified antigen were the first line therapy . Results: After follow up period of three months in 21(47%) children out of 38 with allergy an secretory otitis the complete recovery of middle ear function was seen. After follow up period of 6 months in 27 (61%) children was noticed complete recovery and the rest of 17 children underwent surgical therapy. Discussion and Conclusion: Allergy screening is not conventional tool in diagnosis of secretorz otiti media. The results of this study as well as results of other clinicall studies implies to introduction allergzy tests in clonicall diagnostic procedure Antiallergic therapy can contribute to conservative management of disease and decrease the number of patient for surgical therapy.

Background: Administration of meropenem to penicillin-allergic patients who might benefit from this treatment is usually avoided because of a 47.4% rate of cross-reactivity to imipenem, the prototype of the carbapenem class of β-lactam antibiotics, demonstrated in a single study on the basis of positive responses to skin tests with imipenem reagents. However, recent studies of ours have demonstrated a very low rate of cross-reactivity between penicillins and both meropenem and imipenem in adults. Objective: To assess cross-reactivity and tolerability of meropenem in children with documented penicillin allergy. Methods: One hundred and eight consecutive children who had suffered a total of 129 immediate reactions (120 urticarial and/or angioedematous manifestations and 9 anaphylactic shocks) to penicillins and had positive results to skin tests for at least one of the penicillin reagents tested underwent skin tests with meropenem and negative subjects were challenged with it. Results: One subject (0.9%) displayed a positive intradermal test to meropenem. The remaining 107 subjects with negative skin tests to meropenem tolerated challenges. Challenges were not followed by full therapeutic courses. Conclusions: Our results demonstrate a low rate of cross-reactivity between penicillins and meropenem. Therefore, the practice of avoiding meropenem in children with immunoglobulin E-mediated hypersensitivity could be abandoned; in those who especially require meropenem treatment, prophylactic skin tests are advisable, because negative results indicate tolerability.

Chemically modified allergens (allergoids) have found use in both traditional and novel forms of immunotherapy of allergic disorders. Novel forms of immunotherapy include local allergen delivery, via the gastrointestinal tract. This study conveys the gastrointestinal stability of three types of mugwort pollen allergoids under simulated conditions of the gut. Allergoids of the pollen extract of Artemisia vulgaris were obtained by means of potassium cyanate, succinic and maleic anhydride. Gastrointestinal tract conditions (saliva, and gastric fluid) were simulated in accordance with the EU Pharmacopoeia. The biochemical and immunochemical properties of the derivatives following exposure to different conditions were monitored by determining the number of residual amino groups with 2,4,6-trinitrobenzenesulfonic acid, SDS PAGE, immunoblotting and inhibition of mugwort-specific IgE. Exposure to saliva fluid for 2 min did not influence the biochemical and immunochemical properties of the derivatives. In the very acidic conditions of the simulated gastric fluid, the degree of demaleylation and desuccinylation, even after 4 h exposure, was low, ranging from 10 to 30 %. The digestion patterns with pepsin proceeded rapidly in both the unmodified and modified samples. In all four cases, a highly resistant IgE-binding protein the Mwof which was about 28-35 kD, was present. Within the physiological conditions, no new IgE binding epitopes were revealed, as demonstrated by immunoblot and CAP inhibition of the mugwort specific IgE binding. An important conclusion of this study is the stability of the modified derivatives in the gastrointestinal tract of patients, within physiological conditions. The means that they are suitable for use in much higher concentrations in local forms of immunotherapy than unmodified ones. U ovom radu su prikazani rezultati ispitivanja stabilnosti tri tipa alergoida polena pelina u simuliranom želudačnom soku. Koristeći kalijum-cijanat anhidrid ćilibarne i anhidrid maleinske kiseline, napravljeni su alergoidi polena pelina (Artemisia vulgaris). Saliva i želudačni sok su simulirani na osnovu evropske farmakopeje. Biohemijske i imunohemijske osobine derivata posle izlaganja različitim uslovima, praćene su: određivanjem broja slobodnih amino grupa u reakciji sa TNBS, SDS PAG elektroforezom, imunoblotom i određivanjem pelin-specifičnog imunoglobulina E (IgE). Izlaganje salivi u trajanju od 2 minuta ne utiče na biohemijske i imunohemijske osobine derivata. U kiseloj sredini želudačnog soka ne dolazi do značajnog demaleilovawa i desukcinilovanja. Čak i posle četvoročasovnog izlaganja, taj procenat je u opsegu 10-30 %. Alergoidi pelina se trenutno digestuju pepsinom, sa izuzetkom visoko rezistentne proteinske trake molekulske mase 28-35 kD, koja odgovara važnom IgE-vezujućem proteinu polena pelina. Imunoblotom i CAP-inhibicijom je pokazano da, u okviru fizioloških uslova, ne dolazi do stvaranja novih IgE-vezujućih epitopa. Hemijska stabilnost modifikovanih derivata u simuliranim uslovima želudačnog soka omogućuje da se tokom imunoterapije mogu primenjivati veće doze alergoida nego nemodifikovanog ekstrakta polena pelina.