International Archives of Allergy and Immunology最新文献

Introduction: An increasing number of studies have demonstrated that dynamic changes in lipid species can affect allergic diseases; however, the causal relationship and mediating role of immune cells remain unclear.

Methods: We conducted a bidirectional two-sample mendelian randomization (MR) analysis using genome-wide association study (GWAS) data on 179 lipid species (n = 7,174) and three types of allergic diseases including allergic rhinitis (AR) (n = 370,158), allergic asthma (n = 219,753), and allergic conjunctivitis (n = 377,277). The principal model used was the inverse variance-weighted approach, and a series of sensitivity analyses were conducted to ensure the robustness of the results. We used a two-step MR approach to assess whether the causal effect was mediated by immune cells (n = 3,757).

Results: Sterol ester and sphingomyelin played pathogenic roles in allergic asthma, AR, and allergic conjunctivitis; however, the effective subtypes differed. Among them, CD45RA- CD4+ mature T cells and CCR2 on CD14+ CD16+ monocytes affected the promoting impact of sterol ester's metabolism on allergic asthma and AR with different mediating proportions, while the role of sphingomyelin may not involve the immune cells. Moreover, we observed that HLA-DR on CD33- HLA DR+ myeloid cells, CD11b on CD66b++ myeloid cells, and IgD+ CD38- B cells played the most mediating effect of phosphatidylethanolamine (O-18:2_20:4) in allergic asthma, phosphatidylinositol (16:0_18:1) in AR, and phosphatidylethanolamine (18:0_18:2) in allergic conjunctivitis.

Conclusion: This MR study provides evidence for specific lipid species associated with the risk of allergic diseases, especially sterol esters, and identifies the immune cells that mediate this causal relationship.

Introduction: Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by eczematous lesions and severe itching. However, its pathogenesis has not yet been fully elucidated. The aim of this study was to investigate the causal relationship between plasma proteins and AD, as well as to identify and quantify the potential roles of immune cell phenotypes as mediators.

Methods: We utilized summary-level data from genome-wide association studies and conducted a two-sample Mendelian randomization (MR) analysis involving 4,907 circulating plasma proteins, 731 immune cell phenotypes, and AD. Initially, we conducted bidirectional univariate MR analyses to forecast causal effects linking circulating plasma proteins and AD. Subsequently, we employed a two-step MR analysis to scrutinize the immune cell phenotypes that could mediate these effects. The inverse variance weighted was the main method employed for MR analysis, while the Cochran's Q test and MR-Egger intercept test were used to assess the presence of heterogeneity and pleiotropy, respectively. We then determined whether our results could be influenced by individual single-nucleotide polymorphisms using the "leave-one-out" test.

Results: Positive correlations were observed between KRT1, IL18R1, and SEMA6A and the risk of AD, whereas BDH2, ADAMTS3, ANKRD1, TIAM1, MID2, and IFNA16 all showed negative correlations with the risk of AD. Mediation analysis indicated that CD8 on CM CD8br cells acted as a mediator between IFNA16 and AD, with a mediation effect proportion of 11.2%. In addition, sensitivity analyses did not reveal significant heterogeneity or level pleiotropy.

Conclusion: Our findings indicated the presence of a one-way causal relationship between the circulating plasma protein IFNA16 and AD. This study also explored immune cell phenotypes that may serve as mediators, offering novel insights into the etiology, pathogenesis, and potential clinical interventions in AD. Nevertheless, these findings need to be validated by clinical and laboratory studies.

Introduction: Cow's milk (CM) is one of the most common food allergens in Japan. The oral food challenge (OFC) of CM is important for the definite diagnosis of children with CM allergy, and it is recommended to be actively and safely performed in individuals with low CM-sIgE levels. This study aimed to investigate the safety of low-dose CM-OFC in individuals with low CM-sIgE levels and discuss the prognostic factors and appropriate approaches for assessing the starting doses of CM-OFC in these individuals.

Methods: We retrospectively analyzed 6,929 OFC tests conducted between January 1, 2017, and December 31, 2021; of which, 1,390 were CM-OFC tests. The characteristics, OFC-positive rates, CM loading, and related factors were analyzed in 138 cases involving low CM-sIgE levels. Stepwise OFC tests were conducted according to the food allergies guidelines in Japan using an open and unblinded method.

Results: Among 138 individuals with low CM-sIgE levels, 110 (79.7%) passed the OFC test without any symptoms. Among the cases with OFC-positive status, 50.0% (14/28) cases showed symptoms with low-dose OFC (30-105 mg CM protein). Moreover, complete CM elimination was associated with a significantly high OFC-positive rate, and 60.0% (12/20) of the cases involving complete CM elimination showed symptoms with low-dose OFC.

Conclusion: Eighty percent of the patients with low CM-sIgE levels safely completed the OFC test. Nevertheless, careful observation is essential during low-dose OFC test in cases with low CM-sIgE levels, especially in the cases with complete elimination. The starting dose of the OFC test should be reevaluated, and modified using baked milk or a lower dose of CM to ensure safety and early outgrowth of CM allergy.

Introduction: So far, no definitive conclusions have been reached regarding the preventive effect of moisturizers on atopic dermatitis (AD). The variability in results may be due to differences in skin care methods, including bathing and washing, among studies and study design. In hot and humid Japan, bathing and gauze washing have been routinely practiced from the neonatal period, but this may impair the skin barrier function. To address this gap, we determined whether a combination of minimally invasive cleaning methods and moisturizing may prevent AD in infants in Japan.

Methods: Mothers of children born between January and September 2019 were instructed in traditional skin care methods (control group; 132 subjects), and mothers of children born between January and September 2020 were instructed in a new skin care method combining less invasive washing and moisturizing (intervention group; 140 subjects). Mothers and babies with and without a history of allergy were recruited, and the incidence of AD at 1 year of age was investigated by questionnaire.

Results: Skin care-related behaviors such as face washing, hand washing, and use of moisturizers were more frequent in the intervention group than in the control group. At 6 and 12 months of age, there was no difference in the incidence of AD between the two groups. However, for children born between January and March, the prevalence of AD at 12 months was significantly lower in the intervention group than in the control group (2.9% vs. 21.2%, p = 0.0253).

Conclusions: This study suggests that for children born during dry and cold seasons, strengthening the skin barrier function early in life through routine skin care with less invasive washing and moisturizing may prevent AD in Japan. Appropriate skin care practices for newborns and infants may vary in regions and environments.

Introduction: Hereditary alpha-tryptasemia (HαT) is associated with postural orthostatic tachycardia syndrome (POTS), hypermobile Ehlers-Danlos syndrome (hEDS), and mast cell activation syndrome (MCAS). While POTS, hEDS, and MCAS have all demonstrated increased prevalence of autoimmunity, this has not been investigated in HαT populations. Our objective was to describe the prevalence of autoantibodies in individuals with HαT.

Methods: We retrospectively studied a cohort of patients with positive genotyping for HαT at a tertiary-care allergy clinic. Demographic data including previous autoimmune history and autoantibody serologies were extracted on chart review. A literature search was conducted to determine the prevalence of specific autoimmune and autoantibody prevalences in the general population. We compared the proportions of autoantibody positivity and established autoimmune diseases in our cohort of HαT individuals against those in general populations.

Results: We identified 101 patients with HαT. Median age was 43 years (range 15-75), and most were female (87/101; 86.1%). Prevalence of self-reported drug hypersensitivity was 52/101 (52.5%) patients. The proportion of individuals with HαT with positive tTG antibody (3/61, 4.9%) was significantly higher than that reported in the general population (133/16,667, 0.8%) (p < 0.001). The prevalence of systemic lupus erythematosus (SLE) (1/101, 1%) and celiac disease (5/101, 5%) in our cohort were found to be significantly higher than the prevalence in the general population (194/96,996, 0.2% [p = 0.035] and 26/2,845, 0.9% [p < 0.001], respectively).

Conclusion: Patients with HαT have increased prevalence of celiac disease, SLE, and positive anti-tTG serology, as well as self-reported drug hypersensitivity, relative to general populations.

Introduction: Alanyl-glutamine (Ala-Gln) is a compound known for its protective effects in various tissue injuries. However, its role in asthma-related lung injuries remains underexplored. This study investigates the mechanisms by which Ala-Gln modulates sDPP4-induced airway epithelial-mesenchymal transition and ovalbumin (OVA)-induced asthma in a mouse model.

Methods: An asthma model was established in female C57BL/6 J mice by using OVA. CD4+ T cells and bronchial epithelial cells (BECs) were isolated from the spleen and bronchi of the mice, respectively. Interventions included recombinant sCD26/sDPP4 protein, Ala-Gln, and EX527 (a SIRT1 inhibitor). Flow cytometry was used to assess Th17 and Treg cell populations. Mice were treated with Ala-Gln, EX527, and budesonide (BUD). Histopathological changes in lung tissues were evaluated using hematoxylin-eosin and Masson staining. White blood cell counts were measured with a hematology analyzer. The expression levels of DPP4, IL-17, SIRT1, SMAD2/3, N-cadherin, E-cadherin, MMP9, and α-SMA proteins were analyzed.

Results: Treatment with recombinant sCD26/sDPP4 resulted in decreased E-cadherin expression in BECs and increased levels of α-SMA, MMP9, and N-cadherin, effects that were mitigated by Ala-Gln. Ala-Gln also prevented the reduction in SIRT1 expression in BECs and the increase in Th17 cell differentiation induced by recombinant sCD26/sDPP4. EX527 administration alongside Ala-Gln reversed these changes and enhanced the phosphorylation of SMAD2/3 through SIRT1 signaling. BUD alone reduced inflammation and fibrosis in bronchial tissue and lowered the Th17/Treg ratio in peribronchial lymph nodes. The therapeutic effect of BUD was further improved with concurrent Ala-Gln treatment.

Conclusion: Ala-Gln can inhibit BEC fibrosis and Th17 cell differentiation mediated by recombinant sCD26/sDPP4 through the SIRT1 pathway. Combined with BUD, Ala-Gln enhanced therapeutic efficacy in OVA-induced asthma in mice, which could offer improved outcomes for asthmatic patients with elevated DPP4 levels.

Introduction: Esculentoside A (EsA) is one of the main components of the traditional Chinese medicine Phytolacca esculenta. The possible mechanism of action of EsA in the treatment of lupus nephritis (LN) was explored by observing the effects of EsA on CD19+ IL-35+regulatory B (IL-35+Breg) cells.

Methods: Twenty-four MRL/lpr mice were randomly divided into control, EsA, and EsA+IL-12p35 antibody groups. Mice were administered the respective treatments intraperitoneally once a day for 4 weeks. The urine protein/creatinine ratio (UPCR) and blood creatinine (Cr) and IL-35, IL-10, and IL-17 expression levels were measured. Body and spleen weight were measured to calculate the splenic index (SI). Flow cytometry was performed to determine the proportion of CD19+ IL-35+ Breg cells in the spleen. Hematoxylin-eosin and PASM-Masson staining of renal tissues were performed, and the "Austin" acute index (AI) system for LN was determined.

Results: The most severe conditions were seen in mice in the control group, with the highest UPCR, Cr, and IL-17 levels and SI and AI scores; the most severe renal histopathology, and the lowest proportion of CD19+ IL-35+ Breg cells and IL-35 and IL-10 levels. This was followed by the EsA+IL-12p35 antibody group. The EsA group had the lowest UPCR, Cr, and IL-17 levels and SI and AI scores; the mildest renal lesions; and the highest proportion CD19+ IL-35+ Breg cells and IL-35 and IL-10 levels.

Conclusion: EsA delayed the progression of LN by promoting the proliferation of CD19+ IL-35+ Breg cells, upregulating the expression of IL-35, and decreasing the secretion of IL-17.

Introduction: The objective of this study was to investigate the prevalence, characteristics, and risk factors of acquired punctal stenosis (APS) in adult patients with allergic conjunctivitis (AC).

Methods: This observational case series study included 210 adult AC patients at Zhongshan Ophthalmic Center. The demographic data were collected, and the ocular manifestations were assessed. Morphologies of AC patients' lacrimal puncta were evaluated and graded using the modified grading system by slit-lamp microscopy.

Results: There was 69.0% (145/210) of adult AC participants suffering from APS. Stenotic lacrimal puncta were present in 49.3% (414/840), with grade IIa being the most common (54.6%). Abnormal upper lacrimal puncta were more frequent than lower ones (89.0% vs. 73.1%, p = 0.001). AC patients with APS were significantly older than those without APS (p < 0.001). The percentage of patients with tear meniscus height (TMH) >0.3 mm was 40% in the APS group, compared to 12.5% in the non-APS group (p < 0.001). The age (OR = 1.589, 95% CI: 1.109-2.276, p = 0.012) and TMH (OR = 3.449, 95% CI: 1.224-9.719, p = 0.019) were positively associated with the occurrence of APS.

Conclusion: APS, especially the stenosis of upper lacrimal punctum, is frequently observed in the AC patients. Increased age and widened TMH are associated with the prevalence of APS in adult AC patients, suggesting a potential relationship between the long-term and recurrent course of AC and the development of APS.

Introduction: Peanut allergy is the main food allergy in childhood and poses significant health concerns. This study aimed to critically evaluate the effectiveness and safety of oral immune therapy (OIT) using crushed peanuts versus peanut puffs.

Methods: Children with an allergist diagnosed peanut allergy based on a history of an IgE-mediated reaction and a positive skin prick test for peanuts were recruited at the Montreal Children's Hospital and the Children's Clinic located in Montreal. Based on age and personal preference, initial doses of peanut were given in either puff (Bamba) or crushed peanut form. Patients continued the same dose for 2-5 weeks at home, filled out a symptom diary, and returned to the clinic for up-dosing until maintenance was reached (2 teaspoons of peanut butter). A continuation ratio regression model was used to evaluate the effect of the allergen type on the severity of anaphylactic and allergic reactions (ARs) during OIT while adjusting for potential confounders.

Results: Between October 2020 and June 2023, 191 children (59.6% male; median age 1.95 years) were recruited. Most patients (75.1%) had eczema, and 12.7% had asthma. Oral desensitization was performed using one of two strategies according to the allergist: crushed peanut (n = 60 [31.4%]) and peanut puff (n = 131 [68.6%]). Of the participants, the consumption of puff lowered reaction severity by a factor of 3.94 (95% CI, 1.6-9.6), in comparison to crushed peanuts. Older age markedly elevates the adjusted odds of reacting to a particular severity level as compared to a lower level by 1.20 (95% CI, 1-1.4).

Conclusion: Modified peanut desensitization using peanut puffs has shown potential in reducing the severity of ARs in younger children. Older children may experience a higher risk of severe reactions, indicating the need for age-specific approaches to desensitization protocols.

Introduction: Anaphylaxis is a severe allergic reaction which can be difficult to diagnose. Two strategies evaluating changes in tryptase levels were proposed for diagnosing anaphylaxis. Strategy 1 established a threshold of tryptase levels during reaction exceeding 2 ng/mL + 1.2* (baseline tryptase levels) as a rule for detecting anaphylaxis, while strategy 2 established the ratio of tryptase levels during reaction versus baseline tryptase exceeding a threshold of 1.685. We aimed to compare the diagnostic test accuracy of the two strategies in pediatric anaphylaxis.

Methods: We conducted a case-control study. Cases consisted of 89 patients with anaphylaxis who had reaction tryptase and subsequent baseline tryptase measured. Controls consisted of 25 patients with chronic urticaria who had two tryptase measurements. Sensitivity and specificity for each of the strategies were computed and compared using McNemar test. The area under the curve (AUC) between the two strategies was compared using the DeLong test.

Results: The sensitivity and specificity for strategy 1 was 53.3% and 95.0%, respectively. For strategy 2, the sensitivity and specificity was 54.4% and 85.0%, respectively. There was no significant difference between both strategies' sensitivity and specificity. The Delong test determined that the AUC was significantly (p < 0.05) higher for strategy 1 (0.69) than strategy 2 (0.64).

Conclusion: The Delong test determined that strategy 1 was slightly better in validating anaphylaxis diagnosis than strategy 2. However, both strategies demonstrated a low sensitivity <55%.