Allergology International最新文献

Background: Skin reaction patterns vary across patients with cholinergic urticaria (CholU), but their definition, prevalence, and clinical significance remain ill characterized.

Methods: Patients with CholU underwent pulse-controlled ergometry provocation testing to analyze skin reaction patterns and their correlation with location, onset, severity, sweating behaviour, clinical features, disease control, and quality of life (QoL) impairment.

Results: Based on the size, color, spacing, and shape of wheals as well as their surrounding skin responses, we identified six distinct types of CholU skin reactions, which differed in prevalence, from 83% (Type I) to 11% (Type VI) of patients affected. Almost all patients (94%) had ≥1 type of skin reaction pattern. Sweating was reduced in the majority of CholU patients and most prominently reduced in patients with Type VI skin signs (very small, round, red, widely spaced wheals with surrounding anemic halo), which emerged exclusively on the extremities. Type V skin signs (large, irregular, anemic, widely spaced wheals with moderate size erythema) were associated with the most severe clinical presentation and poorest QoL.

Conclusions: Our analysis showed that most patients have more than one type of skin reaction patterns and that different skin signs are linked to distinct features. Future studies should determine any links between treatment response and types of skin signs in CholU.

Allergen-specific IgE is a major mediator of allergic responses and contributes greatly to allergic disease in the human population. Therapies that inhibit the production of IgE would be useful for lessening the burden of allergic disease. A great deal of research has focused on how IgE responses are regulated, and several factors that promote the production of allergic IgE have been characterized. T follicular helper (TFH) cells expressing IL-4 are required for the development of IgE expressing B cells in the germinal center (GC). Ig somatic hypermutation and B cell selection in the GC leads to the development of high affinity allergen-specific IgE that promotes anaphylaxis, a severe form of allergic response. T follicular regulatory (TFR) cells are also found in the GC response and act with TFH cells in the selection of high affinity IgE + B cells. This review examines the current literature on IgE responses and TFR cells. In mouse studies, TFR cells have a suppressive role on IgE responses in allergic airway disease, however TFR cells also play a helper role in the IgE response in food allergy. In human studies, TFR cells correlate with a decreased allergic response but evidence for a direct suppressive role of TFR cells on IgE in vivo is lacking. TFR cells may represent a new target for allergy therapies, but caution must be exercised to promote the suppressor activity of TFR cells and not the helper activity of TFR cells on IgE responses.

Background: The latest guidelines on hypersensitivity pneumonitis (HP) categorise the disease as either fibrotic or non-fibrotic because of the greater clinical utility of this stratification. However, the prevalence and incidence of fibrotic and non-fibrotic HP are unknown. This study assessed the exact prevalence and incidence of fibrotic and non-fibrotic HP in Japan in 2021.

Methods: For adults, the study hospitals were selected by stratified random sampling according to numbers of beds. The sampling rate was set at about 20%. The questionnaire survey was submitted to the target hospitals. For pediatric cases, a survey was distributed to all members of the Japanese Society of Pediatric Pulmonology and Japanese Society of Pediatric Allergy and Clinical Immunology.

Results: Regarding adult cases, in total, 575 facilities responded to the survey, resulting in a response rate of 36.4%. The estimated prevalence and incidence of fibrotic HP were 6.3 and 2.5 per 100,000 population, respectively, versus 3.6 and 2.0 per 100,000 population, respectively, for non-fibrotic HP. Both fibrotic and non-fibrotic HP were more prevalent in southern Japan (Kyushu) and less prevalent in northern Japan (Hokkaido). The incidence of non-fibrotic HP was significantly lower in December than in the other months (relative risk ratio = 0.36, p < 0.001). Three cases of fibrotic HP and five cases of non-fibrotic HP were identified in children.

Conclusions: This study determined the prevalence and incidence of fibrotic and non-fibrotic HP in Japan for the first time.

Background: In many countries, neuro-muscular blocking agents (NMBAs) are the first cause of perioperative anaphylaxis. Epidemiological studies identified pholcodine, a quaternary ammonium-containing opiate as one of the sensitization sources. However, NMBA anaphylaxis exists in countries where pholcodine was unavailable, prompting the hypothesis of other sensitizing molecules, most likely quaternary ammonium compounds (QACs). Indeed, QACs are commonly used as disinfectants, antiseptics, preservatives, and detergents. Occupational exposure to QACs has been reported as a risk factor for NMBA anaphylaxis, but little is known about the sensitization mechanism and the capacity of these molecules to elicit an immune response. We aimed to establish the immunogenicity of QACs representative of the main existing chemical structures.

Methods: We measured the sensitization potential of seven QACs (two polyquaterniums, three alkyl-ammoniums and two aromatic ammoniums) by using two standard dendritic cells (DCs) models (THP-1 cell line and monocyte derived-dendritic cells). The allergenicity of the sensitizing compounds was further tested in heterologous and autologous T-cell-DC co-culture models.

Results: Amongst the seven molecules tested, four could modulate activation markers on DCs, and thus can be classified as chemical sensitizers (polyquaterniums-7 and -10, ethylhexadecyldimethylammonium and benzethonium). This activation was accompanied by the secretion of pro-inflammatory and maturation cytokines. Furthermore, activation by polyquaternium-7 could induce T-cell proliferation in heterologous and autologous coculture models, demonstrating that this molecule can induce a specific CD4⁺ T cell response.

Conclusions: We provide evidence at the cellular level that some QACs can elicit an immune response, which could be in line with the hypothesis of these molecules' role in NMBA sensitization.

Background: The therapeutic effectiveness of dupilumab for severe asthma in real-world settings is yet to be prospectively investigated across multiple institutions, and uncertainties persist regarding predictive factors for its effectiveness. We aimed to assess the effectiveness of dupilumab and identify predictors of its effectiveness in real-world settings using two type-2 biomarkers: FeNO concentration and blood eosinophil count.

Methods: This prospective multicenter study included 103 patients with severe asthma. Exacerbations and respiratory functions were monitored for 24 weeks. Asthma control was evaluated using the Asthma Control Questionnaire-5. Clinical symptoms and their impact on cough and sputum were assessed using the Cough and Sputum Assessment Questionnaire (CASA-Q). Subgroup analyses of type-2 biomarkers were conducted based on FeNO levels and blood eosinophil counts at baseline.

Results: Treatment with dupilumab led to a reduction in exacerbations and enhancement in asthma control, FEV₁, and CASA-Q scores. FEV₁ improvement was correlated with enhancement in the sputum domain of the CASA-Q. Patients exhibiting elevated FeNO levels and blood eosinophil counts demonstrated more significant enhancements in FEV₁. CASA-Q sputum domain scores were significantly higher in the group with elevated eosinophil counts. Regression analysis revealed that FeNO levels and blood eosinophil counts are significant predictors of FEV₁ improvement, with blood eosinophil counts also predicting sputum improvement in patients treated with dupilumab.

Conclusions: Type-2 biomarkers may act as indicators of improvement in FEV₁ and sputum outcomes among patients with severe asthma undergoing dupilumab treatment in real-world settings.

Human T follicular helper (Tfh) cells play a crucial role in orchestrating B cell differentiation, maturation, and immunoglobulin class switching. Recent studies have underscored the presence of Bcl-6 + Tfh cells not only in secondary lymphoid organs but also within tertiary lymphoid structures at inflammatory sites, emphasizing their pivotal role in disease pathogenesis. Furthermore, Tfh cells have been found to transit between lesion sites, lymph nodes, and peripheral blood, as revealed by T cell receptor repertoire analysis. Among Tfh subsets, Tfh2 cells have emerged as central orchestrators in driving the production of IgE and IgG4 from B cells. Their critical role in diseases such as allergy, malignancy, and IgG4-related disease highlights their profound impact on balancing inflammation and immune tolerance. Our current review provides the molecular characteristics of human Tfh cells, the differentiation pathways of Tfh subsets, mechanisms by which Tfh subsets induce IgE and IgG4 production, and their clinical implications in allergy, malignancy, and IgG4-related disease.

IgE antibodies raised against innocuous environmental antigens cause allergic diseases like allergic rhinitis, food allergy, and allergic asthma. While some allergies are often outgrown, others (peanut, shellfish, tree nut) are lifelong in the majority of individuals. Lifelong allergies are the result of persistent production of allergen-specific IgE. However, IgE antibodies and the plasma cells that secrete them tend to be short-lived. Persistent allergen-specific IgE titres are thought to be derived from the continued renewal of IgE plasma cells from memory B cells in response to allergen encounters. The initial generation of allergen-specific IgE is driven by B cell activation by IL-4 producing Tfh cells, but the cellular and molecular mechanisms of the long-term production of IgE are poorly characterized. This review investigates the mechanisms governing IgE production and Tfh activation in the primary and recall responses, towards the objective of identifying molecular targets for therapeutic intervention that durably inactivate the IgE recall response.

Background: Component-resolved diagnostics are used to diagnose food allergies. Currently, reports on sensitization profiles using peach-allergen components in a multicenter setting are lacking. In this study, sensitization profiling of peach allergy was performed to evaluate the clinical utility of each component specific-immunoglobulin E antibody (sIgE ab) test.

Methods: Sixty-seven patients with peach allergy were enrolled at four Japanese centers and classified into a local reaction group (LR) with only oral or pharyngeal mucosal symptoms in 36 patients and a systemic reaction group (SR) without LR in 31 patients. Serum sIgE ab tests to peach crude, Pru p 1, Pru p 3, Pru p 4, Pru p 7, and tree pollen were conducted.

Results: In the receiver operating characteristic curve analysis, Pru p 1 had the highest area under the curve (AUC) for diagnosing LR, followed by Pru p 4, which outperformed peach crude allergen. Pru p 7 had the highest AUC for diagnosing SR, with the other peach allergen components and peach crude allergen showing lower values.

Conclusions: Sensitization to Pru p 1 was associated with LRs, while sensitization to Pru p 7 was associated with SRs; approximately one-third of patients in the SR group tested negative for the titer of peach crude sIgE ab, many of whom tested positive for the titer of Pru p 7 sIgE ab. We conclude that measuring Pru p 1, Pru p 4, and Pru p 7 sIgE ab titers is useful to differentiate LRs and SRs in peach-allergic Japanese patients.

Background: Low-dose (LD) oral food challenge (OFC) with heated cow's milk (CM; 3 mL) effectively prevents CM elimination in children with CM allergy (CMA). We investigated the long-term prognoses after an LD-OFC for CMA.

Methods: Children with immediate CMA symptoms after consuming <25 mL of CM within 2 years of a baseline LD-OFC were retrospectively analyzed. Children who successfully passed the baseline LD-OFC (LD-passing) continued consuming 3 mL of CM at home, whereas those who failed (LD-failing) continued to avoid CM. Dose escalation occurred through stepwise OFCs or gradually at home. CM tolerance was defined as the ability to repeatedly consume ≥100 mL CM without experiencing symptoms; the inability to do so indicated persistent CMA. The prognoses of the LD-passing and LD-failing groups within 3 years of LD-OFC were compared.

Results: Among 113 children, the median age at baseline LD-OFC was 2.8 years; 41 % had an anaphylaxis history, with equal distribution between the LD-passing and LD-failing groups. Three years later, 63 % and 5 % of children demonstrated CM tolerance in the LD-passing and LD-failing groups, respectively (p < 0.001). In the LD-passing group, predictors of persistent CMA were older age (adjusted hazard ratio [95 % confidence interval], 1.37 [1.00-1.88]), higher CM-specific IgE level (2.95 [1.30-6.68]) and other food allergies (2.34 [1.12-4.90]).

Conclusions: Failure in LD-OFC is associated with persistent CMA, whereas successful LD-OFC outcomes are associated with a favorable prognosis thereafter, irrespective of a history of anaphylaxis.

Background: Type I allergy to sweat is involved in the pathogenesis of atopic dermatitis (AD) and cholinergic urticaria (CholU), with MGL_1304 from Malassezia globosa being the major causative antigen. Currently, no standard diagnostic test exists for sweat allergy that uses serum.

Methods: The ImmunoCAP (iCAP) system to measure antigen-specific IgE was developed using recombinant MGL_1304 (rMGL_1304). Using a positive histamine release test (HRT) against the semi-purified sweat antigen (QR) as a criterion for diagnosing sweat allergy, the diagnostic usefulness of anti-MGL_1304 IgE detected through iCAP was analyzed in comparison with conventional anti-Malassezia antigen m227 IgE (anti-m227 IgE).

Results: The iCAP system with rMGL_1304 detected anti-MGL_1304 IgE in serum samples without detection of non-specific reactions. In 93 patients with AD or CholU, of which 58 were HRT-positive, anti-MGL_1304 IgE titers correlated with histamine release levels in HRT against QR better than anti-m227 IgE titers. The cutoff value for sweat allergy diagnosis was 1.55 U_A/mL for anti-m227 IgE (sensitivity: 79.3 %; specificity: 65.7 %) and 0.671 U_A/mL for anti-MGL_1304 IgE (sensitivity: 84.5 %; specificity: 80.0 %). Clinical features of AD and CholU were partially associated with anti-m227 IgE and anti-MGL_1304 IgE titers but not with histamine release in HRT using QR.

Conclusions: Anti-MGL_1304 IgE detection using iCAP is simple and can help diagnosis of sweat allergy with better accuracy than conventional anti-Malassezia antigen IgE.