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BackgroundPrimary ciliary dyskinesia (PCD) is a motile ciliopathy, whose symptoms include airway infections, male infertility and situs inversus. Apart from the typical forms of PCD, rare syndromic PCD forms exist. Mutations of the X-linked OFD1 gene cause several syndromic ciliopathies, including oral-facial-digital syndrome type 1, Joubert syndrome type 10 (JBTS10), and Simpson-Golabi-Behmel syndrome type 2, the latter causing the X-linked syndromic form of PCD. Neurological and skeletal symptoms are characteristic for these syndromes, with their severity depending on the location of the mutation within the gene.ObjectivesTo elucidate the role of motile cilia defects in the respiratory phenotype of PCD patients with C-terminal OFD1 mutations.MethodsWhole-exome sequencing in a group of 120 Polish PCD patients, mutation screening of the OFD1 coding sequence, analysis of motile cilia, and magnetic resonance brain imaging.ResultsFour novel hemizygous OFD1 mutations, in exons 20 and 21, were found in men with a typical PCD presentation but without severe neurological, skeletal or renal symptoms characteristic for other OFD1-related syndromes. Magnetic resonance brain imaging in two patients did not show a molar tooth sign typical for JBTS10. Cilia in the respiratory epithelium were sparse, unusually long and displayed a defective motility pattern.ConclusionConsistent with the literature, truncations of the C-terminal part of OFD1 (exons 16–22) almost invariably cause a respiratory phenotype (due to motile cilia defects) while their impact on the primary cilia function is limited. We suggest that exons 20–21 should be included in the panel for regular mutation screening in PCD.

The rising prevalence of food allergies, particularly to peanuts and tree nuts, poses significant challenges for pediatric health worldwide. These allergens are among the leading causes of severe allergic reactions, including anaphylaxis, often manifesting in early life. This review synthesizes the current knowledge on the immune mechanisms underlying these allergies, emphasizing the interplay between genetic, immunologic, and environmental factors in shaping allergic sensitization. Advances in prevention strategies, including early allergen introduction, have been critically evaluated. Predictive and diagnostic methodologies, from traditional IgE evaluation to cutting-edge proteomics and metabolomics approaches, have been explored to identify biomarkers that predict allergy onset and severity. By unraveling early immunological and molecular signatures, this study aimed to summarize the early prediction, prevention, diagnosis, and treatment of peanut and tree nut allergies, ultimately contributing to more effective interventions and a better quality of life for affected children.

IntroductionIntroducing baked milk into the diet of children with cow’s milk protein allergy (CMPA) has been shown to potentially accelerate the development of tolerance to non-heated milk. However, there is no standardised milk ladder (ML) protocol, and different scientific societies across countries recommend varying versions. This study aims to assess the effectiveness and safety of the four-step ML (4-ML) compared with the six-step ML (6-ML) in children with IgE-mediated CMPA.Methods and analysisWe will perform an open-label randomised trial with two parallel arms in two departments of the same academic hospital. A total of 92 children with IgE-mediated CMPA will be allocated in a 1:1 ratio to introduce cow’s milk into their diet according to either 4-ML or 6-ML with a 4-week break period between subsequent steps. Oral food challenge (OFC) with tested products at each subsequent step of the ML will be conducted in hospital settings. The primary outcome will be the percentage of children with tolerance to non-heated cow’s milk proteins defined as no allergic reaction to raw cow’s milk (120–240 mL depending on the age of the patient) during the last OFC; measured at the end of the 12-week observation period for the 4-ML and 20-week observation period for the 6-ML. Secondary outcomes will include the percentage of children with a negative OFC to each ML step; the percentage of children with anaphylaxis (both those who were treated and those who were not treated with epinephrine); the percentage of children with exacerbation of atopic dermatitis; growth; compliance; and quality of life of the caregivers and parents’ anxiety about adverse events during their child’s OFC.Ethics and disseminationThe bioethics committee of the Medical University of Warsaw, Poland, approved this protocol (KB/107/2024). The findings will be published in a peer-reviewed journal and submitted to relevant conferences no later than 1 year after data collection.Trial registration numberNCT06664918.

IntroductionSesame allergy, though with low prevalence, can result in severe, potentially life-threatening reactions and poses challenges in allergen avoidance due to hidden sources. In the majority of patients, sesame allergy persists and there is currently no effective long-term treatment available. Therefore, oral immunotherapy (OIT) is a promising alternative approach to managing sesame allergy. In this study protocol, we present a randomised controlled trial evaluating the efficacy and safety of OIT with low-dose sesame protein in paediatric patients. The study’s aim is to compare OIT with a 300 mg maintenance dose of sesame protein against controls.Methods and analysis39 participants aged 3–17 with IgE-mediated sesame allergy confirmed by oral food challenge will be enrolled into the study. The trial will be conducted at the Paediatric Hospital of the Medical University of Warsaw, Poland. The study comprises two arms—sesame OIT and control. In the sesame OIT group, interventions will be administered once daily for up to 18 months. During the first phase, the dose will be escalated every 2–4 weeks, and in the second phase, the maintenance dose of 300 mg sesame protein will continue for 3 months. Members of the control group will receive standard treatment, which includes an elimination diet and will remain under observation for 1 year. The primary outcome is the proportion of participants tolerating a single dose of 4000 mg of sesame protein during the final oral food challenge in the experimental group versus the control group. Secondary outcomes assess adverse events, changes in immunological parameters and the maximum tolerated doses of sesame protein in each group.Ethics and disseminationThis study has been approved by the Ethics Committee of the Medical University of Warsaw (approval number: KB/269/2023). Results will be published in peer-reviewed journals and disseminated via presentations at international conferences.Trial registration number NCT06261554.

To compare the efficacy and safety of two sesame protein maintenance doses (300 mg vs 1200 mg) in pediatric oral immunotherapy (OIT) for sesame allergy. In this randomized, single-center, open-label trial (NCT05158413), 26 children aged 4-17 years with confirmed sesame allergy were allocated 1:1 to receive either 300 mg or 1200 mg sesame protein as maintenance therapy following dose escalation. Inclusion criteria included positive skin prick test (SPT) and/or elevated sesame-specific IgE (sIgE), as well as clinical reactivity during oral food challenge (OFC). The primary endpoint was the proportion of patients tolerating 4000 mg of sesame protein at the end-of-treatment OFC. Secondary outcomes included changes in immunologic markers (SPT wheal size, sIgE, IgG4) and safety. The rate of negative OFCs in our study (81.8% in the high-dose group and 69.2% in the low-dose group; p = 0.649) was comparable to outcomes reported in previous sesame OIT trials (19-22), indicating similar efficacy across different maintenance dose regimens. Both groups showed significant reductions in SPT wheal size and increases in sesame-specific IgG4 (p < 0.005), with no significant changes in sIgE levels. The rate of World Allergy Organization (WAO) grade I adverse events per dose was comparable between groups (4.74% vs 3.88%, p = 0.706), with three WAO grade II events (2 high-dose, 1 low dose) and no grade III or adrenaline-requiring reactions reported. This interim analysis, based on a limited sample size, suggests that both low- and high-dose sesame OIT regimens are consistent with being effective and well tolerated in children, with similar immunologic responses and a favorable safety profile. Given the pilot nature of the study, the results should be interpreted as preliminary and hypothesis-generating, warranting confirmation in larger, long-term trials to optimize sesame OIT dosing strategies.

IntroductionThe prevalence of food allergies, particularly IgE-mediated allergies, is rising in developed countries, with cashew nut allergy emerging as a significant public health concern due to its potential for severe anaphylaxis and frequent association with atopic disorders. Cashew nuts are among the most common allergens in Europe and Australia, often involving cosensitisation with pistachios, hazelnuts and other allergens. Diagnosis relies on clinical history, measurement of specific IgE (sIgE) levels, skin prick tests (SPT) and oral food challenges (OFCs). Current management strategies focus on allergen avoidance and emergency interventions, whereas oral immunotherapy (OIT) represents a promising approach to desensitisation. Recent studies, including the NUT CRACKER trial, have reported high desensitisation rates with cashew OIT, although these are associated with a risk of adverse events. This study introduces a novel randomised controlled trial aimed at evaluating the efficacy and safety of cashew immunotherapy in children.Methods and analysisThis randomised, open-label, parallel-group trial, with a 2:1 allocation ratio, will be conducted at the Department of Paediatric Pneumology and Allergology, Medical University of Warsaw, Poland. Thirty-nine children, aged 4–17 years, with confirmed IgE-mediated cashew allergy via open OFC will be enrolled. Participants in the experimental group will undergo OIT, which involves gradually increasing doses of cashew protein up to a maintenance dose of 1200 mg. The duration of OIT will range from 12 to 60 weeks, depending on individual baseline tolerance. The control group will receive standard management, including strict cashew avoidance and emergency response strategies to accidental exposure, for 1 year.The primary endpoint is to determine the proportion of participants tolerating a 4043 mg dose of cashew protein at the study’s end in the OIT group compared with the control group. Secondary outcomes include evaluating the safety profile of OIT, assessing changes in laboratory markers such as sIgE and IgG4 levels for cashew and the major cashew allergen Ana o 3, analysing basophil activation test responses and measuring changes in SPT wheal diameter at baseline and study completion.Ethics and disseminationThe study has been approved by the Ethics Committee of the Medical University of Warsaw (approval number: KB/267/2023). Study findings will be published in peer-reviewed journals and presented at international conferences.Trial registration numberNCT06328504.

Primary immunodeficiencies (PIDs) are rare disorders of the immune system encompassing inborn errors of immunity. Primary antibody deficiencies constitute the largest group of PID with common variable immunodeficiency (CVID) being the most common symptomatic form. Combined immunodeficiencies (CID) accompanied by antibody deficiency can mimic CVID and these patients need the verification of the final diagnosis. Respiratory involvement, especially interstitial lung disease (ILD), poses a relevant cause of morbidity and mortality among patients with PID and in some cases is the first manifestation of immunodeficiency. In this study we present a retrospective analysis of a group of children with primary immunodeficiency and ILD - the clinical, radiological, histological characteristics, treatment strategies and outcomes. Eleven children with PID-related ILD were described. The majority of them presented CVID, in three patients CID was recognized. All patients underwent detailed pulmonary diagnostics. In eight of them histological analysis of lung biopsy was performed. We noted that in two out of 11 patients acute onset of ILD with respiratory failure was the first manifestation of the disease and preceded PID diagnosis. The most common histopathological diagnosis was GLILD. Among the analyzed patients three did not require any immunosuppressive therapy. All eight treated children received corticosteroids as initial treatment, but in some of them second-line therapy was introduced. The relevant side effects in some patients were observed. The study demonstrated that the response to corticosteroids is usually prompt. However, the resolution of pulmonary changes may be incomplete and second-line treatment may be necessary.

(1) Pediatric inflammatory multisystem syndrome (PIMS) is a relatively rare complication of coronavirus disease (COVID-19). So far, it is unclear why COVID-19 in children has usually mild or asymptomatic courses, whereas PIMS, which develops several weeks after COVID-19, is a serious life-threatening condition. (2) In this proof-of-concept study, using the ELISA method, we compared selected clinical and immunological parameters in small groups of children with PIMS and COVID-19. Children with various inflammatory diseases were included as a control. (3) Patients with PIMS revealed significantly higher levels of pro-inflammatory molecules (C-reactive protein and IL-6) and markers of heart injury (troponin I and N-terminal prohormone of brain natriuretic peptide) as compared to other groups. Moreover, these markers correlated with increased levels of soluble receptors for tumor necrosis factor (sTNF-R1 and sTNF-R2). (4) Our observation may be a step forward to better understand the phenomenon of mild COVID-19 in children and its severe complications in PIMS. It is hypothesized that the delayed inflammation results in excessive cardiomyocyte damage and the release of sTNF-R1 and -R2. Therefore, possibly the involvement of the TNF pathway in PIMS could be explored as a potential therapeutic target. However, further studies are required to validate this approach.

(1) Peanut allergy is associated with high risk of anaphylaxis which could be prevented by oral immunotherapy. Patients eligible for immunotherapy are selected on the basis of a food challenge, although currently the assessment of antibodies against main peanut molecules (Ara h 1, 2, 3 and 6) is thought to be another option. (2) The current study assessed the relationship between the mentioned antibodies, challenge outcomes, skin tests and some other parameters in peanut-sensitized children. It involved 74 children, divided into two groups, based on their response to a food challenge. (3) Both groups differed in results of skin tests, levels of component-specific antibodies and peanut exposure history. The antibody levels were then used to calculate thresholds for prediction of challenge results or symptom severity. While the antibody-based challenge prediction revealed statistical significance, it failed in cases of severe symptoms. Furthermore, no significant correlation was observed between antibody levels, symptom-eliciting doses and the risk of severe anaphylaxis. Although in some patients it could result from interference with IgG4, the latter would not be a universal explanation of this phenomenon. (4) Despite some limitations, antibody-based screening may be an alternative to the food challenge, although its clinical relevance still requires further studies.

IgE-mediated cow’s milk allergy is a significant clinical problem. It may be persistent in a large percentage of children. This allergy is associated with restrictive diet, limitations in social activities and anxiety arising from the fear of accidental exposure to the allergen and life-threatening anaphylaxis. Currently, elimination diet and education of the child and their caregivers are the basic approaches in IgE-mediated cow’s milk allergy. However, this strategy does not modify the natural course of allergy. The so-called milk ladder and specific immunotherapy with cow’s milk, which is still an experimental treatment, are methods allowing for increasing the reactivity threshold. Both treatments are causal and can lead to permanent milk tolerance in the patient. The scheme of dietary expansion in a child with IgE-mediated cow’s milk allergy using the milk ladder involves introducing food products containing milk that is processed to a varying degree. This method assumes that patients who can introduce baked dairy products into their diet develop tolerance to increasingly higher doses of allergen over time and, at the same time, less thermally processed products. Oral immunotherapy with cow’s milk involves administering the allergen, usually in the form of unprocessed milk, in increasing amounts until the target dose is reached. The article discusses the possibilities of inducing tolerance to cow’s milk proteins in IgE-mediated allergy using the milk ladder and oral immunotherapy, along with advantages and limitations of such approaches.