European annals of allergy and clinical immunology最新文献

Summary: Background. Common Variable Immunodeficiency (CVID) is a primary immunodeficiency disorder characterized by B-cell dysfunction and immunoglobulin production deficiency. Dysregulation of interleukin-17 (IL-17) and its receptor IL-17RA have been reported in various immune disorders. This study aimed to investigate the expression of IL-17RA in innate immune cells of CVID patients and its correlation with clinical manifestations. Methods. A cross-sectional study included 22 CVID patients and 14 age- and sex-matched healthy controls. IL-17RA expression was assessed in various immune cell subsets using flow cytometry. Demographic and clinical data were collected, and statistical analysis was performed. Results. CVID patients had elevated IL-17RA expression in neutrophils, non-classical monocytes, and dendritic cells compared to healthy controls. Patients with a history of intestinal microbial colonization, particularly with Campylobacter jejuni and Giardia intestinalis, showed significantly higher IL-17RA expression in innate cells. Elevated IL-17RA expression in monocytes and dendritic cells also correlated with higher fecal calprotectin levels in CVID patients, regardless of microbial colonization. Conclusions. The study suggests that despite previous reports of reduced circulating Th17 cells and IL-17 levels in CVID patients, IL-17RA expression in innate cells may be elevated, potentially indicating altered IL-17 signaling. This heightened IL-17RA expression could contribute to a persistent pro-inflammatory state, possibly due to microbial translocation or other inflammatory factors. The association of IL-17RA expression with gastrointestinal microbial colonization and its correlation with fecal calprotectin underscores the complexity of IL-17RA's role in CVID pathophysiology. Further research in larger cohorts could elucidate the implications of IL-17RA expression in both infectious and non-infectious inflammatory aspects of CVID.

Summary: Background. In patients whose chronic urticaria (CU) cannot be controlled with omalizumab 300 mg and antihistamines, the dose can be increased up to 600 mg. The study aimed to compare the clinical characteristics of patients receiving 300 mg versus higher doses of omalizumab, and to evaluate baseline predictors for updosing. Methods. A total of 159 patients who have been followed up at a tertiary care allergy center and received omalizumab for at least 12 months were included. The clinical characteristics of those who received the standard-dose omalizumab (Group 1) were compared to the ones who received therapy over the standard dose (Group 2).  Results. A total of 139 (87%) were in Group 1, and 20 (13%) were in Group 2. CU duration at baseline was shorter in Group 2. Chronic inducible urticaria was present in 2%, and 40% of the patients in Group 1 and 2, respectively. Elevated D-dimer level was associated with high-dose omalizumab use (p < 0.001). Area under the curve in the ROC analysis was 0.812 and the cutoff value of D-dimer level was 0.46 mg/dl (p = 0.001, sensitivity and specificity 67%, and 84%, respectively). The anti-TPO positivity was higher in patients with low IgE (31% vs 8%, p = 0.008). Conclusions. Nearly one in every ten patients required higher doses of omalizumab therapy. D-dimer level seems to be a predictor for omalizumab updosing and unresponsiveness to standard dose. IgG-anti-TPO positivity and low IgE do not predict the need for dose escalation; however, this result should be strengthened with a larger number of patients.

Summary: Background. Chronic spontaneous urticaria (CSU) response to anti-IgE treatment can be rapid, late or absent. Recently, potential mechanisms of activation of mast cells alternative to FceRI, including mas-related G protein-coupled receptor X2 (MRGPRX2), activation of coagulation cascade, and activation of eosinophils have been described. We measured several potential in-vitro markers, including well-known MRGPRX2 activators, in sera of patients CSU both responding and not responding to omalizumab. Methods. D-dimer, substance P (SP), eosinophil cationic protein (ECP), soluble MRGPRX2, IgE anti-FceRI, IgE anti-FceRII, IgG anti-FceRI and IgG anti-FceRII were measured in 32 patients with severe CSU at baseline and one week after the start of omalizumab therapy, and in 20 healthy controls. Results. At baseline CSU patients showed significantly higher levels of D-dimer, IgE anti-FceRI, IgG anti-FceRI, and ECP (p < 0.001 in all cases), and significantly lower levels of soluble MRGPRX2 (p = 0.009) than controls. The two groups showed similar levels of IgG and IgE to FceRII and SP. One week after the first omalizumab administration there was a significant drop of IgE anti-FceRI (p < 0.001) and D-dimer (p = 0.028), in early responders. SP increased in all CSU patients (p < 0.001) irrespective of the final response to omalizumab. IgE anti-FceRI response at one week was associated with the final response to omalizumab (OR:0.12 [95%CI 0.01-1.06]). Conclusions. Severe CSU is associated with high plasma levels of several biomarkers including D-dimer, IgE anti-FceRI, IgG anti-FceRI and ECP and low levels of soluble MRGPRX2. IgE anti-FceRI response at one week may predict the final response to omalizumab.

Summary: Background. Children with milk and egg allergies have outcomes in which three-quarters are tolerant to baked forms of the allergenic food. Identifying predictors of tolerance to baked foods for IgE-mediated immediate-type reactions may guide the early introduction of baked allergens to diet and tolerance development. This study explores factors associated with early tolerance to baked foods. Methods. We retrospectively analyzed patients with IgE-mediated immediate-type food allergy in infancy who either became tolerant to the baked form before two years or remained reactive after two years. Results. We examined 143 patients solely with IgE-mediated immediate-type egg and/ or milk allergies excluding those with atopic dermatitis. 76 (42 egg-allergics; 34 milk-allergics) achieved tolerance, and 67 (38 egg-allergics; 29 milk-allergics) were reactive beyond the age of two. Receiver operating characteristic analysis determined cut-off values for specific-Immunoglobulin E (sIgE) levels (kU/L) predicting mild phenotype at first admission: egg white-sIgE ≤ 7.39, milk-sIgE ≤ 5.99, and casein-sIgE ≤ 4.99, with AUC values of 0.703, 0.716, and 0.749, respectively. Conclusions. This study identifies key prognostic factors for tolerance to baked allergen for IgE-mediated immediate-type reactions, providing valuable insights to determine the patients who need more intensive care versus the ones who don't need baked allergen avoidance early in their life from their initial admission at infancy.

Summary: Spice allergies are often under-recognized and under-researched, leading to delays in diagnosis and treatment. Cross-reactivity with other plant allergens further complicates accurate diagnosis. This literature review seeks to systematize and analyze current data on hypersensitivity to spices, including pepper, cumin, oregano, anise, mustard, and other seasonings. The review covers research published from 2010 to 2023 in peer-reviewed journals, books, and conference proceedings, sourced from databases such as PubMed, Scopus, Web of Science, and Google Scholar. The main pepper allergens are PR-10 proteins, profilins and defensins. They can cause cross-allergic reactions with pollen and other plant allergens. Cumin allergens belong to the PR-10 family and can provoke allergic reactions. Cross-reactivity between cumin and other umbelliferae is common. Oregano contains Bet v 1 allergens and profilins, often leading to cross-allergies with other spices and plants. Allergies to anise are less common but can be a serious problem due to cross-reactivity with birch pollen. Mustard is one of the most allergenic spices. These proteins can cause severe reactions even in small amounts. Diagnosis is carried out using skin prick tests and blood tests for specific IgE antibodies. Cross-reactivity among spices and other allergens complicates the diagnosis and management of spice allergies. This review will be useful for the development of personalized dietary recommendations for patients, accounting for cross-reactivity and individual sensitization profiles.

Summary: Background. Oral immunotherapy (OIT) is a promising strategy for severe and persistent cow's milk (CM) allergy. However, clinical experience concerning long-term follow-up is scarce. The objective is to assess long-term efficacy and safety of maintenance phase of OIT in real-life. Methods. Prospective study of children with severe IgE-mediated CM allergy that underwent CM-OIT, and were followed-up by the authors, up to 15 years. Complete desensitisation was defined when maintenance dose of 200 mL daily was achieved. Characterization (clinical and laboratory) was performed before and after OIT during follow-up.  Results. Thirty-three patients enrolled: 58% male, 70% asthmatics and 67% with previous history of CM-anaphylaxis. Mean age at onset of CM-OIT was 7±2.8 years. Complete desensitisation was ensured in 94% (free diet with dairy 200mL of CM or equivalent). During maintenance phase 79% developed allergic reactions, with anaphylaxis in 33%, including exercise-induced anaphylaxis in 15% and with cheese intake in 15%. We stress that eosinophilic esophagitis appeared in 12%. Specific IgE levels and skin prick tests (SPT) to CM and casein have significantly decreased, and in most patients (61%) SPT became negative. When available, specific IgG4 levels have significantly increased. Conclusions. This real-life study supports long-term efficacy and safety of CM-OIT. CM-OIT had a high success rate, allowing diet without restrictions with persistence of the effect up to 15 years. However, one-third of patients experienced anaphylaxis during maintenance phase. CM-OIT should always be performed by allergy experts and only motivated families should be enrolled, since long-term follow-up is required, and daily intake of CM is needed to ensure desensitization.

Summary: Background.Soy allergy represents a diagnostic challenge, particularly when mediated by Gly m 4, a PR-10 protein known for its cross-reactivity with birch pollen allergens. Traditional diagnostic methods, including skin prick tests (SPTs) and specific IgE assays, often lack sensitivity or specificity, especially for Gly m 4-mediated allergies. Methods. In this study, the basophil activation test (BAT) was evaluated as a tool to distinguish true allergy from mere sensitization to Gly m 4. Results.A total of four patients sensitized to Gly m 4 and Bet v 1 (PR-10 of soy and birch) were included in this study. Two patients were confirmed allergic to soy based on positive BAT results with Gly m 4 and soy total extract, correlating with clinical symptoms of allergy. Conversely, two other patients were determined to be sensitized but clinically tolerant, as BAT results were negative, consistent with their symptom-free status during oral food challenges. Conclusions. The study highlights the limitations of traditional diagnostic methods, which often yielded false-negative or inconclusive results, and underscores the BAT's ability to provide functional evidence of allergen reactivity. We demonstrate the utility of BAT in identifying clinically relevant Gly m 4-mediated soy allergies. By enabling precise differentiation between allergy and sensitization, the BAT emerges as a valuable diagnostic tool, complementing molecular allergen-specific IgE assays and offering a safer and more specific alternative to oral food challenges.

Summary: Background. Asthma control can be influenced by several factors, including obstructive sleep apnea (OSA). The literature reports variable prevalence and magnitude of OSA impact on asthma outcomes. The aim of our study is to analyze the frequency of high-risk for OSA in asthma patients and its impact on disease severity and control. Methods. We conducted a cross-sectional study at an Allergy Department with adult asthma patients recruited while undergoing routine lung function tests. Data on sex, age, body mass index, allergen sensitization, smoking habits, risk of OSA (using the Berlin questionnaire), rhinitis control (through CARAT), asthma severity (based on GINA 2023), asthma control (using the ACT), adherence to asthma treatment (through Treatment Adherence Measure) and pulmonary function test results were collected. Results. We included 216 patients, predominantly women (70.4%), with a median (P25-P75) age of 29.0 (21.0-45.0) years, of whom 28.2% were on GINA treatment levels 4-5. In 75.5% of cases asthma was controlled. High-risk for OSA was identified in 21.8% of patients. Asthma patients with high-risk for OSA were more likely to have uncontrolled [(47.8%; n = 22) vs (15.8%; n = 26); p less than 0.001] and more severe disease [(44.7%; n = 21) vs (23.7%; n = 40), p = 0.006]. In multivariable analysis, high-risk for OSA (OR 2.81 [95%CI 1.1.28-6.17], p = 0.010), sex (women) (OR 5.21 [95% CI 1.70-15.96], p = 0.004), uncontrolled rhinitis (OR 3.65 [95%CI 1.38-9.64], p = 0.009) and GINA asthma treatment steps 4-5 (OR 2.46 [95%CI 1.15-5.26], p = 0.020) were associated with uncontrolled asthma. Conclusions. It is crucial to actively investigate OSA, especially in patients with uncontrolled and more severe forms of asthma.