European annals of allergy and clinical immunology最新文献

Summary: Long-lived plasma cells (LLPCs) constitute a specialized and durable arm of humoral memory. While their role in maintaining long-term IgG and IgA immunity is firmly established, their contribution to IgE-mediated allergic disease remains clinically unproven. Nevertheless, recent advances in LLPC biology-accelerated substantially since 2021-have shown that IgE⁺ LLPC-like cells do exist in human bone marrow and chronically inflamed tissues, providing an immunological basis for exploring their potential involvement in persistent sensitization. LLPCs arise through tightly orchestrated developmental programs and rely on survival niches shaped by stromal cells, cytokines and metabolic adaptations. These features allow continuous antibody secretion for years or decades, independently of antigen re-exposure. Their metabolic resilience and resistance to apoptosis make them among the most durable effector cells in adaptive immunity. In parallel, several mechanisms already known to support IgE persistence-early-life programming of type-2 responses, Treg/Tfr disequilibrium, sequential class switching from IgG1 memory, and rapid recall from non-IgE memory B cells-form a robust framework capable of sustaining long-term allergic sensitization irrespective of LLPC involvement. Within this architecture, the confirmed presence of IgE⁺ long-lived plasma cells offers a biologically plausible, though not yet clinically validated, explanation for the remarkable stability of IgE profiles observed in many allergic conditions. Considering LLPCs within the broader context of IgE persistence highlights an area of growing immunological relevance while underscoring that their precise contribution to allergic disease remains to be determined.

Summary: Background. The diagnosis of immediate drug allergy (DA) relies on a combination of skin tests (ST), drug provocation tests (DPT), specific IgE levels (sIgE) and/or basophil activation tests (BAT). We aimed to compare BAT results with those of other allergy tests in patients with suspected immediate DA to a heterogeneous group of drugs, aiming to assess its diagnostic value. Methods. Patients who underwent BAT for suspected immediate DA at our hospital from January 2018 to December 2023 were included. Each case (suspected drug) was classified based on diagnostic tests performed - probable vs. improbable allergy (assessed by ST and/or sIgE only) or confirmed vs. excluded allergy (assessed by DPT). Inter-method agreement was assessed with Cohen's kappa index (κ). Results. Eighty-five patients were included: 51 female (60.0%), median age 53.0 years [interquartile range (IQR) = 33.0, Q1-Q3=31.0-64.0]. Median time elapsed since index reaction was 1.0 year [IQR=3.0, Q1-Q3 = 1.0-3.0]. We identified 112 suspected drugs: out of 16 cases with positive BAT (14.3%), 6 were probable (37.5%) and 1 confirmed allergy (6.3%). From 89 drugs with negative BAT (79.5%), 41 were improbable (46.1%) and 5 excluded allergy (5.6%). Seven agents had an inconclusive BAT (6.3%). A slight agreement (κ = 0.201) between BAT and other studies was observed when combining probable/improbable and confirmed/excluded results (n = 76). When limiting these findings to confirmed/excluded results (n=6), we found a perfect agreement (κ = 1).  Conclusions. We assessed BAT performance in a larger sample than those from previous studies. Slight agreement between methods increased to a perfect agreement when limiting to confirmed cases. Larger studies are needed to establish BAT's diagnostic value.

Summary: NOT AVAILABLE.

Summary: Background. Hereditary angioedema (HAE) is a rare genetic disorder with variable prevalence, characterized by recurrent swelling in various parts of the body, including potential laryngeal attacks, significantly affecting patients' quality of life. Methods. A nationwide, cross-sectional survey study was conducted between December 2023 and June 2024, targeting adults (aged 18 and older). The patients filled out different HAE-related questionnaires. Descriptive statistics were used to analyze and summarize the data. Results. The prevalence of HAE in Croatia is estimated to be 3.10 per 100,000 people. The majority were females, patients with positive family history, and type 1 HAE. The median diagnostic delay was 13 years, with initial attacks typically occurring in adolescence, but diagnosis was often not established until young to middle adulthood. Regarding quality of life, approximately 51% reported a significant impact. Fatigue was prevalent, with 46.9% of patients experiencing mild to moderate levels, and 22.4% suffering from severe fatigue. Most patients reported minimal depression, and 37.7% presented with moderate to severe anxiety. Among employed individuals, a median presenteeism of 20% indicated productivity loss while at work, in contrast to generally minimal absenteeism. Conclusions. Recent more substantial diagnostic efforts and increased awareness are contributing factors to the higher observed prevalence of HAE in Croatia, mainly due to the sustained work of a dedicated patient organization and a well-developed network of national HAE experts. Patients still experience a high disease burden, impaired quality of life, and difficulties with daily activities, which trends also observed in other HAE cohorts worldwide.

Summary: Background. Anaphylaxis is the most severe form of acute systemic allergic reactions. Several recommendations have been proposed to guide and standardize anaphylaxis approach and management. The objective of this study is to characterize a cohort of patients referred through an anaphylaxis fast-track system, to enhance and standardize anaphylaxis patient care. Methods. Observational study including patients with anaphylaxis admitted in the emergency department (ED) and/or referred through the fast-track system (June 2022 - June 2025). Collected data included demographics, clinical presentation, aetiology, treatment, adrenaline autoinjector (AAI) prescription, request for serum tryptase testing, biphasic reactions, diagnosis and follow-up care. Results. Over the 399 patients referred through the fast-track system for specialist evaluation, anaphylaxis was confirmed in 120 patients. Drug-induced anaphylaxis was the most prevalent, with nonsteroidal anti-inflammatory drugs the most reported (46.3%). Food-induced anaphylaxis was the second cause, with shellfish accounting for most cases (63.5%). The most common association of symptoms was mucocutaneous and respiratory symptoms (49.5%). Among the 120 confirmed cases, intramuscular adrenaline was administered in 68.4% (67/98) of patients admitted to ED and AAI in only 18.4% (18/98). Biphasic reactions were only reported in three patients. No fatalities or recurrent episodes were documented. Conclusions. These findings highlight the importance of standardized protocols or fast-track systems for anaphylaxis diagnosis and management, allowing for a rapid recognition, treatment and management of patients. Nevertheless, the need to continually improve medical education and training remains. This study is limited by its selected cohort, the exclusion of primary-care emergency department data owing to coding limitations, and its inherently descriptive design.

Summary: Background. Flaxseed allergy is a rare and potentially underdiagnosed condition. In recent years, sensitization to flaxseed has increased due to its growing presence in the human diet. This study presents three distinct cases of flaxseed allergy and discusses the strengths and limitations of current diagnostic tools in identifying this emerging allergy. Methods. Each case underwent a detailed clinical history followed by an allergological evaluation using in vivo testing (skin prick-to-prick) and in vitro methods (serum specific IgE testing with singleplex and multiplex immunoassays) for flaxseed and other suspected seeds or tree nuts. Results. Case 1: A male patient, previously diagnosed with pumpkin seed allergy, experienced multiple episodes of urticaria and angioedema following ingestion of bread containing unspecified dark seeds. Testing revealed sensitization to flaxseed, pumpkin, sunflower, sesame seeds and storage proteins from soy, walnut, and hazelnut. Case 2: A male patient developed cutaneous symptoms after ingesting an energy bar. Testing showed positivity only to flaxseed, while results for other seeds and tree nuts were negative. Case 3: A female patient with repeated episodes of labial angioedema and anaphylaxis, initially misdiagnosed with sesame allergy, was found to be allergic to flaxseed. Conclusions. Flaxseed allergy remains a rare but emerging condition that is difficult to diagnose, partly due to its frequent omission from ingredient labels and the absence of specific allergenic molecules in commercial diagnostic tests. Future regulatory consideration should evaluate the inclusion of flaxseed among priority food allergens.

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.