Allergy Cohort Research Articles

Nasal secretions trace epithelial type 2 response to allergen-specific immunotherapy.

Allergen-specific immunotherapy (AIT) is a disease-modifying therapy and is effective to reduce the symptoms of grass pollen-allergy. The airway epithelium of these patients releases inflammatory mediators including type-2 cytokines, which are associated with cellular processes involved in the symptomatic response of the affected tissue. Aim of the study was to identify epithelial biomarkers indicating AIT progress. In an exploratory, observational allergy cohort, we longitudinally phenotyped 56 grass pollen-allergic patients undergoing AIT for over three years and 18 controls using nasal secretions at critical time windows during therapy to assess peak-season responses along the course of therapy. Type-2 cytokine protein levels were analyzed using the high-sensitivity multiplex electrochemiluminescence mesoscale technique. The type-2 cytokines CCL26 and POSTN oscillated seasonally, in contrast to TSLP and IL-33. However, only POSTN was reduced over the three-year AIT progression. In addition to POSTN, IL-24 and IL-37 levels were continuously reduced during AIT, while IFN-g and CCL27 were increased. Compared to healthy individuals, AIT did not restore healthy secretion levels but rather induced a novel homeostasis CONCLUSION: Nasal secretions trace the epithelial response during different phases of AIT. We demonstrate that AIT only partially controls the epithelial type 2 cytokine CCL26, which also adapts to seasonal changes, while POSTN and IL-24 are potential indicators of therapy success. Therefore, nasal secretions represent a promising, non-invasive tool for monitoring seasonal progress of AIT.

Clinical utility analysis of the Hoxb8 mast cell activation test for the diagnosis of peanut allergy.

Peanut allergy is among the most severe and common food allergies. The diagnosis has a significant impact on the quality of life for patients and their families. An effective management approach depends on accurate, safe, and easily implementable diagnostic methods. We previously developed a cell-based assay using Hoxb8 mast cells (Hoxb8 MCs) aimed at improving clinical allergy diagnosis. In this study, we assessed its diagnostic performance by measuring blinded sera from a prospectively enrolled and pre-validated peanut allergy cohort. Hoxb8 MCs were passively sensitized with sera from peanut-allergic and peanut tolerant children and adolescents (n = 112). Degranulation of Hoxb8 MCs was quantified upon stimulation with dose-titrated peanut extract by means of flow cytometry, using CD107a as activation marker. The results from the Hoxb8 mast cell activation test (Hoxb8 MAT) were compared to established diagnostic assays such as the skin prick test (SPT), specific IgE (sIgE) levels, and the basophil activation test (BAT). Additionally, serum samples from BAT nonresponders were assessed with the Hoxb8 MAT. Hoxb8 MAT displayed a robust dose-dependent activation to peanut extract, with a cutoff value of ≤5.2% CD107a positive cells. The diagnostic accuracy was highest at allergen concentrations ≥100 ng/mL, with an area under the receiver operating characteristic curve (AUROC) of 0.97, 93% sensitivity, and 96% specificity, outperforming traditional SPT and sIgE tests. When compared to BAT, Hoxb8 MAT exhibited comparable diagnostic efficacy. Moreover, sera from BAT nonresponders were accurately classified into allergics and nonallergics by the Hoxb8 MAT. The Hoxb8 MAT demonstrated a very good diagnostic precision in patients prospectively assessed for peanut allergy comparable to the fresh whole blood-based BAT. Additionally, it demonstrated its value for accurate classification of BAT nonresponders into allergic and nonallergic individuals. Further investigations into its utility in the routine clinical setting are warranted.

Prenatal exposure to perfluoroalkyl and polyfluoroalkyl substances and childhood bone mineral density: A prospective birth cohort study

Background and aimPerfluoroalkyl and polyfluoroalkyl substances (PFAS) have demonstrated potential toxicity in skeletal development. However, the relationship between prenatal PFAS exposure and offspring bone health remains unclear in epidemiological studies. Therefore, we aim to investigate whether prenatal exposure to PFAS is associated with bone mineral density (BMD) in offspring. MethodThis study population included 182 mother-child pairs in the Shanghai Obesity and Allergy Cohort, enrolled during 2012–2013. 10 PFAS were measured by liquid chromatography-mass spectrometry (LC-MS) in cord plasma. The child's spinal BMD was measured using a dual-energy X-ray absorptiometry (DXA) scanner at the age of 8. Multivariable linear regression models were used to estimate the associations between individual PFAS concentrations (as a continuous variable or categorized into quartiles) and child BMD. Bayesian kernel machine regression (BKMR) was employed to explore the joint effects of PFAS mixtures on BMD. ResultsAmong the 10 PFAS, 8 of them had a detection rate >90% and were included in the subsequent analysis. We observed no significant associations between individual PFAS (as a continuous variable) and spinal BMD in 8-year-old children using the multivariable linear regression model. When treated as quartile categories, the second and fourth quartiles of perfluorobutane sulfonate (PFBS) was associated with higher BMD in the first lumbar vertebra, compared with the lowest quartile. BKMR analysis revealed no association between the PFAS mixture and child BMD. ConclusionWe observed no associations of prenatal PFAS exposure with child BMD at 8 years of age. Given the inconsistent epidemiological evidence, further research is needed to confirm these findings from other studies or elucidate the potentially toxic effects of PFAS on bone.

Immune Hypersensitivity Is Associated With Higher Graft Failure Rate After Osteochondral Allograft Transplantation of the Knee

To analyze the effects of 1 or more patient-reported allergies on clinical outcomes, in particular graft failure rate, and patient-reported outcomes (PROs) following osteochondral allograft transplantation (OCA) of the knee. Retrospective review of patients who underwent knee OCA from August 2010 to May 2021 with a minimum of 2-year follow-up. Patients were initially divided into 2 cohorts: those with at least 1 allergy and those without any allergies. Clinical outcomes assessed included graft failure, reoperation rates, deep vein thrombosis/pulmonary embolism, and manipulation under anesthesia/lysis of adhesions (MUA/LOA). PROs assessed, including the visual analog scale (VAS) for pain and satisfaction, the Knee injury and Osteoarthritis Outcome Score (KOOS), and return to sport rates, were compared. In total, 285 patients were included with a mean clinical follow-up of 4.8 ± 2.0 years. The allergy cohort had a significantly higher rate of graft failure (P= .008). In a regression analysis controlling for confounding variables, graft failure remained significantly associated with the presence of medication allergies (odds ratio [OR], 3.631; 95% CI, 1.139-11.577; P= .029). Furthermore, an increasing number of allergies were associated with an increased rate of graft failure (OR, 1.644; 95% CI, 1.074-2.515; P= .022). There was no difference in rate of reoperation, complications, infection, and MUA/LOA. Of the 100 patients who completed PROs, there was no difference in VAS satisfaction, pain, and any of the KOOS outcome scores or return to sport. The presence of 1 or more patient-reported allergies was shown to be significantly associated with OCA graft failure. Furthermore, an increasing number of patient-reported allergies were associated with a higher rate of graft failure. However, there were no significant differences in VAS satisfaction or pain, KOOS symptom, quality of life, pain, or return to sport in patients with at least 1 patient-reported allergy and those without allergies. Level III, retrospective cohort study.

Patients with higher numbers of allergies have lower levels of anti-inflammatory cytokines and increased pain at the time of ACL reconstruction

BackgroundSynovial fluid biomarkers are well studied indicators of inflammation and healing in the setting of orthopedic injuries. However, it has not been studied if patients with one or more allergies have a difference in the concentrations of synovial fluid inflammatory cytokines compared to patients without allergies. The purpose of the current study is to analyze the concentration of 10 pro- and anti-inflammatory cytokines in the synovial fluid of isolated ACL injury patients with and without at least one allergy. Study DesignRetrospective Case-Control. MethodsA database of patients who underwent surgery for isolated ACL injury between September 2011 and July 2023 was analyzed. All patients had SF aspirated from the operative knee prior to the surgical incision and the concentrations of pre- and anti-inflammatory biomarkers were quantified. From this cohort, 24 patients were identified to have allergies by chart review. These patients were matched 1:1 to 24 patients without allergies based on age and sex. ResultsThere were no significant differences between the allergy and no allergy cohorts with respect to age (28.5 ± 10.3 vs. 29.5 ± 8.9, p = 0.76) and sex (70.8 % female vs. 70.8 % female, p = 1.00). The allergy cohort had a decreased concentration of TIMP-1 (492.41 ± 616.20 ng/mL vs. 1041.48 ± 942.04 ng/mL, p = 0.03) and IL-1Ra (101.70 ± 93.37 pg/mL vs. 359.94 ± 399.77 pg/mL, p = 0.01) compared to patients without allergies. A linear regression analysis found a significant association between increasing number of patients reported allergies and decreasing concentration of TIMP-1 (β = -231.59, p = 0.03) and IL-1Ra (β = -71.69p = 0.03) concentrations when controlling for age and sex. Finally, the allergy cohort was found to have a significantly higher value for the VAS pain scale at the time of surgery (26.84 ± 24.73 vs. 7.37 ± 10.98, p < 0.01) compared to those without an allergy. ConclusionPatients undergoing ACL reconstruction with at least one allergy were found to have decreased concentrations of the anti-inflammatory cytokines TIMP-1 and IL-1Ra in their synovial fluid compared to those without allergies on the day of surgery. Furthermore, an increase in total number of allergies was found to be an associated with a decrease in TIMP-1 and IL-1Ra levels. Finally, the allergy cohort also had a higher value for the VAS pain scale at the time of surgery, implicating the role of a patient’s innate immune system to their biologic and symptomatic response to injury.

Food allergy: Trends in the development of allergen-specific immunotherapy technologies

BACKGROUND: Food allergy is an urgent problem for public health around the world. One of the most promising methods of food allergy treatment is allergen-specific immunotherapy.&#x0D; AIM: to analyze the results of clinical studies on the effectiveness and safety of modern allergen-specific immunotherapy technologies in the treatment of food allergies published over the past three years.&#x0D; MATERIALS AND METHODS: A search and analysis of scientific publications was carried out using resources cataloging biomedical scientific literature: PubMed and eLibrary. The review includes original studies published between January 1, 2020 and December 31, 2022.&#x0D; RESULTS: The review made it possible to systematize the data accumulated over the past three years, reflecting the main trends in allergen-specific immunotherapy of food allergy. The analysis of studies showed modern approaches to oral and epicutaneous immunotherapy and affected the efficacy and safety of these types of treatment. In food allergy cohorts, the allergen-specific immunotherapy approach of oral and epicutaneous allergen-specific immunotherapy has been shown to be highly effective in achieving tolerance and desensitization to the food trigger it was revealed that epicutaneous allergen-specific immunotherapy is characterized by a high level of adherence of patients to treatment.&#x0D; CONCLUSION: It is necessary to continue conducting large-scale clinical studies on modern methods of allergen-specific immunotherapy in patients with food allergies to form standardized therapy protocols.

Severe food allergy reactions are associated with α-tryptase

Increased TPSAB1 copy numbers encoding ⍺-tryptase are associated with severe reactions in adults with Hymenoptera venom allergy, systemic mastocytosis, and idiopathic anaphylaxis. The primary objective was to assess the association between ⍺-tryptase and severity of food allergy. A total of 119 subjects underwent tryptase genotyping; 82 of them were from an observational food allergy cohort at the National Institute of Allergy and Infectious Disease (NIAID), and 37 were from a cohort of children who reacted to peanut oral food challenge (OFC) at Lurie Children's Hospital of Chicago. The primary predictor was presence or absence of ⍺-tryptase. The primary outcomes for both cohorts were measures of severity of food allergy reaction. Secondary outcomes included OFC symptom scores (Bock/Practical Allergy [PRACTALL] and Severity Grading Score for Acute Reactions [SGSAR]). Correlation between total α-tryptase isoforms and OFC scores was also assessed to account for gene dosage effects. Among the subjects in the NIAID cohort, the presence of ⍺-tryptase was associated with a higher prevalence of food-triggered anaphylaxis than in those with only β-tryptase (P= .026). Similarly, only 1 of 6 subjects in the OFC cohort with only β-tryptase (17%) had a severe reaction, whereas 20 of 31 of subjects with α-tryptase (65%) had a severe reaction (P= .066). Subjects with ⍺-tryptase also had higher total SGSAR scores than did the subjects with no ⍺-tryptase (P= .003). In addition, there were also significant positive correlations between ⍺-tryptase isoform copy numbers and both higher total SGSAR and Bock/PRACTALL OFC scores (P= .008 and P= .003, respectively). The presence of α-tryptase in subjects is correlated with a higher prevalence of anaphylaxis or severe reaction to food than in subjects without any α-tryptase.

COVID-19 Incidence and Disease Course Among Patients at an Allergy Department.

Since the coronavirus pandemic in 2020, there is not much reported about the disease course of COVID-19 in patients with allergic diseases. The aim of this study was to investigate the cumulative incidence and severity of COVID-19 among patients from the allergy department compared with the general Dutch population and people from their household. We conducted a comparative longitudinal cohort study. In this study patients of the allergy department were included with their household members as a control group. Data from the beginning of the pandemic were systematically obtained through questionnaires by telephonic interviews and retrieved from electronic patient files between October 15, 2020 and January 29, 2021. Main outcomes were confirmed SARS-CoV-2 infection, disease duration, hospitalization, intensive care admission, and mortality. Questions regarding applied social distancing measures were inventoried as well. Three hundred and eighty nine patients (median age 39.1 (18.7-84.7) years, 69.9% female) and 441 household members (median age 42.0 (18.0-91.5), 44.1% female) were included. The cumulative COVID-19 incidence in patients was higher compared with the general population (10.5% vs 5.6%, P < .001). In total, 41 (10.5%) patients attending the allergy clinic compared to 38 (8.6%) household members were infected with SARS-CoV-2 (P = .407). Median disease duration was 11.0 (0.0-61.0) days in patients compared to 10.5(1.0-232.0) days in household members (P = .996). The cumulative COVID-19 incidence in patients from the allergy cohort was higher compared with the general Dutch population, but similar compared with household members. There was no difference in symptoms, disease duration, or hospitalization rate between the allergy cohort and their household members.

Prospective Assessment of Penicillin Allergy (PAPA): Evaluating the performance of penicillin allergy testing and post-delabelling outcomes among Hong Kong Chinese.

Incorrect penicillin 'allergy' labels predispose patients to adverse outcomes but are under-recognised in many Asian countries. Studies on performance and post-delabelling outcomes of penicillin allergy evaluation among Chinese remain scarce. To evaluate the diagnostic performance of allergy testing and post-delabelling outcomes among Chinese patients in a prospective penicillin allergy cohort - Prospective Assessment of Penicillin Allergy (PAPA). All adult patients (age ≥ 18 years) who underwent penicillin allergy evaluation between January 2020 to December 2021 were recruited and prospectively reviewed by both medical records and individual interviews at least 6 months after delabelling or allergy confirmation. Out of 372 patients who completed penicillin allergy evaluation, 335 (90%) patients were delabelled. The overall negative predictive value of penicillin skin testing was 95%, but lower for patients with non-immediate type reactions (88%). History of non-immediate symptom onset (OR = 4.501 [95%CI = 2.085-9.716], p < 0.001) and duration since index reaction (OR = 0.942 [95%CI = 0.899-0.987], p = 0.012) were associated with positive skin testing. After at least 6 months, 60 (18%) of de-labelled patients had received penicillins again without any adverse reactions. Fluoroquinolone-use was significantly lower among delabelled patients compared to those with penicillin allergy (38[11%] vs 11[30%], p = 0.004). After at least 6 months, one in six delabelled patients already received penicillins again safely, with significantly lower fluoroquinolone usage. None experienced adverse reactions. History of non-immediate onset and shorter duration since index reaction were associated with genuine allergy. In patients with severe non-immediate reactions, skin tests should be supplemented with thorough clinical history and adjunct diagnostic evaluations.

Low dose rivaroxaban therapy in aspirin allergic patients undergoing percutaneous coronary intervention

Abstract Aspirin in combination with a P2Y12 inhibitor is the mainstay of treatment post percutaneous coronary intervention (PCI) for coronary artery disease (CAD). However, patients who are allergic to or intolerant to aspirin pose a therapeutic challenge especially when encountered in the setting of acute coronary syndrome. Aspirin desensitization strategies have been used in clinical practice to build tolerance prior to coronary intervention but clearly are not practical in the setting of ACS or significant symptomatic CAD. Low dose rivaroxaban (2.5 mg twice a day) has been previously shown to be safe in combination with a P2Y12 inhibitor post ACS compared to aspirin. We therefore sought to see if low dose rivaroxaban is a safe and effective alternative to aspirin in patients post PCI who are unable to take aspirin.This study aims to compare the efficacy (Major adverse cardiovascular events (MACE)) and safety (Bleeding events as defined by Bleeding Academic Research Consortium (BARC) criteria) in patients with confirmed aspirin allergy who were treated with low dose rivaroxaban therapy in place of aspirin in combination with P2Y12 inhibitors post PCI. Methods This was a single center observational study which looked at 50 cases of patients with aspirin allergy (47 cases) or significant confirmed aspirin intolerance (3 cases) who underwent PCI between December 2017 and February 2022. Patients were advised to take low dose rivaroxaban 2.5 mg twice a day as an alternative to aspirin 75 mg once a day. A comparator group of 50 matched patients without aspirin allergy who underwent PCI during the same time period and treated with standard aspirin therapy (75mg) along with a P2Y12 inhibitor. Outcomes over follow-up were MACE (mortality, myocardial infarction, stroke, and unscheduled revascularisation) and bleeding events defined by–BARC criteria. Results The median age of the aspirin allergy cohort was 62 years old with typical comorbidities associated with CAD. The cohort included a case mix of ACS and stable angina.The P2Y12 inhibitor in the majority of cases (76%) was Clopidogrel; Ticagrelor was used in 20% of cases and Prasugrel in 4% cases. No differences existed between the rivaroxaban and matched patient groups. The median follow-up as 626 days (Interquartile range 237–549). The duration of low dose rivaroxaban therapy was for 12 months with a P2Y12 in 72%, 1–3 months for 22% and finally continued long term (with P2Y12 discontinuation at 12 months) in 6%. No difference existed in the incidence of MACE between the low dose rivaroxaban group (12%) compared to the matched cohort (10% p=0.266). No difference in bleeding outcomes (any bleeding event BARC type &amp;gt;0) were seen (14% in rivaroxaban and 16% in control, p=0.329). Conclusions This study provides more supporting evidence that low dose rivaroxaban therapy is an alternative to aspirin when used in combination with a P2Y12 inhibitor post PCI. Funding Acknowledgement Type of funding sources: None.

Peanut anaphylaxis in 2022: Decoupling epinephrine usage from emergency department evaluation

Peanut anaphylaxis in 2022: Decoupling epinephrine usage from emergency department evaluation

Latex Allergy as an Independent Risk Factor for Prosthetic Joint Infection.

In response to increasing rates of self-reported latex allergies, changes have been made to prevent anaphylaxis in the operating room, including the use of latex-free gloves. However, the impact of these changes on the risk of prosthetic joint infection (PJI) after arthroplasty is unclear. This study evaluated whether documented latex allergy is an independent risk factor for PJI and aseptic revision surgery after total hip arthroplasty (THA) and total knee arthroplasty (TKA). A retrospective matched cohort study was conducted with an administrative claims database. A total of 17,501 patients who underwent TKA and had documented latex allergy were matched 1:4 with 70,004 control subjects, and 8221 patients who underwent THA and had documented latex allergy were matched 1:4 with 32,884 control subjects. Multivariable logistic regression showed that patients who had TKA and had a latex allergy showed significantly higher risk of PJI at both 90 days (odds ratio [OR], 1.26) and 1 year (OR, 1.22) and significantly higher risk of aseptic revision TKA at 1 year (OR, 1.21) after surgery compared with control subjects. Patients who had THA and had a latex allergy had significantly higher risk of PJI at 1 year (OR, 1.19) compared with control subjects. Rates of aseptic revision THA were higher in the latex allergy cohort but statistically comparable (P>.05). Latex allergy was associated with significantly increased risk of PJI and aseptic revision after TKA and significantly increased risk of PJI after THA. More work is needed to determine whether these risks can be mitigated or if latex allergy is an inherent, nonmodifiable risk factor requiring modification to typical arthroplasty pathways. [Orthopedics. 2022;45(4):244-250.].

Immediate Hypersensitivity to Fluoroquinolones: A Cohort Assessing Cross-Reactivity.

BackgroundFluoroquinolones are the second-most prescribed antimicrobial and are frequently associated with causing hypersensitivity reactions. Existing evidence regarding cross-reactivity of fluoroquinolones is limited, offering clinicians little guidance in understanding the implications of selecting an in-class alternative among patients with histories of allergic reactions to fluoroquinolones. The aim of this study was to compare the frequency of immediate hypersensitivity reactions to ciprofloxacin, levofloxacin, and/or moxifloxacin among patients with a history of immediate hypersensitivity to a different fluoroquinolone.MethodsThis retrospective chart review included adult patients with a history of an immediate hypersensitivity reaction to ciprofloxacin, levofloxacin, and/or moxifloxacin and a documented prescription for a different fluoroquinolone. The primary outcome was documentation of a hypersensitivity reaction upon second fluoroquinolone exposure.ResultsA total of 321 cases met inclusion criteria. Of these cases, 2.5% experienced an immediate hypersensitivity reaction after second fluoroquinolone exposure to ciprofloxacin, levofloxacin, and/or moxifloxacin. Within the ciprofloxacin, levofloxacin, and moxifloxacin index allergy cohorts, the frequency of cross-reactivity was 2.5%, 2.0%, and 5.3%, respectively.ConclusionsOur data suggest that patients with a history of immediate hypersensitivity reaction to ciprofloxacin, levofloxacin, and/or moxifloxacin are at low risk of experiencing a cross-reaction when exposed to a different fluoroquinolone. Avoidance of all fluoroquinolones in this patient population may not be warranted.

The predictive value of self-reported allergies for reoperation after index hip arthroscopy.

ABSTRACTThe purpose of this study is to compare the rate of reoperation after index hip arthroscopy for symptomatic femoroacetabular impingement in patients with, and without, at least one self-reported allergy. Data were collected prospectively in 1468 patients whose records were retrospectively reviewed. After the application of inclusion and exclusion criteria, two cohorts were formed: (i) a study cohort (n = 261) composed of patients with a self-reported allergy and (ii) a control cohort. (n = 666). The allergy cohort had a significantly larger [P < 0.001] reoperation rate (24.1% [63/261]) compared to the control cohort (9.6% [64/66]). Univariate analysis (UVA) and multivariate analysis (MVA) were then performed to better understand the implications of allergy status on the arthroscopic outcome. On UVA the presence of an allergy increased the odds of reoperation after index hip arthroscopy by 2.99 [OR (95% CI): 2.99 (2.04, 4.39); P < 0.001] and for each additional allergy a patient reported, their odds of subsequent surgery increased by 1.27 per allergy [OR (95% CI): 1.27 (1.15, 1.39); P < 0.001]. However, on the MVA, allergy status was not an independent risk factor for reoperation. These findings suggest that allergy status is associated with a higher reoperation rate, however, allergy status alone cannot prognosticate the risk of subsequent surgery. Therefore, allergy status and its association with future surgery after hip arthroscopy should be considered in the context of multiple patient-specific factors that influence the surgical outcome. An understanding of this association enables patient-centered care and will strengthen the physician–patient relationship.

Omega-5 and Gamma Gliadin are the Major Allergens in Adult-Onset IgE-Mediated Wheat Allergy: Results from Thai Cohort with Oral Food Challenge.

BackgroundVarious clinical patterns based on routes of sensitization and sensitized allergens are reported in adult-onset IgE-mediated wheat allergy. There is still a paucity of data on IgE-bound wheat allergen profiles in wheat challenge-proven adult-onset wheat allergic cases. Therefore, we aim to identify the major sensitized allergens in Thai adult-onset wheat allergic patients whose first symptom occurred after the age of 18 years despite previous tolerance.MethodsThis cross-sectional pilot study recruited patients from the Thai Adult-onset IgE-mediated Wheat Allergy Cohort (TAWAC). The sera of patients with mostly challenge-proven cases were selected for allergen study, including ImmunoCAP and IgE-bound gliadins along with glutenins profiles. The IgE-bound proteins were identified by liquid chromatography-tandem mass spectrophotometry (LC-MS/MS). Direct binding of IgE to recombinant gliadin and glutenin was performed to confirm the results of immunoblot and LC-MS/MS.ResultsEleven wheat-dependent exercise-induced anaphylaxis (WDEIA) and 4 typical wheat allergy (WA) patients were enrolled. Serum IgE from >50% of bound proteins had a molecular weight ranging from 35 to 55 kDa in both gliadin and glutenin extracts. Further, ELISA demonstrated that γ-gliadin and ω5-gliadin were the most important major allergens. Other major allergens include α/β-gliadin, HMW glutenin, and possibly α-amylase inhibitor or LWM glutenin. Gamma-gliadin sensitization was found in all WA patients (4/4), while ω-5 gliadin was found in all WDEIA patients (11/11) from ELISA.ConclusionWheat γ-gliadin and ω-5 gliadin are major wheat allergens among adult-onset wheat allergy patients in Thailand. Component-resolved diagnosis using γ-gliadin might be helpful in high suspicion of wheat allergy.

An exhausted phenotype of TH 2 cells is primed by allergen exposure, but not reinforced by allergen-specific immunotherapy.

Studies show that proallergic TH 2 cells decrease after successful allergen-specific immunotherapy (AIT). It is likely that iatrogenic administration of allergens drives these cells to exhaustion due to chronic T-cell receptor stimulation. This study aimed to investigate the exhaustion of T cells in connection with allergen exposure during AIT in mice and two independent patient cohorts. OVA-sensitized C57BL/6J mice were challenged and treated with OVA, and the development of exhaustion in local and systemic TH 2 cells was analyzed. In patients, the expression of exhaustion-associated surface markers on TH 2 cells was evaluated using flow cytometry in a cross-sectional grass pollen allergy cohort with and without AIT. The treatment effect was further studied in PBMC collected from a prospective long-term AIT cohort. The exhaustion-associated surface markers CTLA-4 and PD-1 were significantly upregulated on TH 2 cells upon OVA aerosol exposure in OVA-allergic compared to non-allergic mice. CTLA-4 and PD-1 decreased after AIT, in particular on the surface of local lung TH 2 cells. Similarly, CTLA-4 and PD-1 expression was enhanced on TH 2 cells from patients with allergic rhinitis with an even stronger effect in those with concomitant asthma. Using an unbiased Louvain clustering analysis, we discovered a late-differentiated TH 2 population expressing both markers that decreased during up-dosing but persisted long term during the maintenance phase. This study shows that allergen exposure promotes CTLA-4 and PD-1 expression on TH 2 cells and that the dynamic change in frequencies of exhausted TH 2 cells exhibits a differential pattern during the up-dosing versus the maintenance phases of AIT.

Self-reported allergies correlate with a worse patient-reported outcome after hip arthroscopy: a matched control study.

Patient-reported outcome measures (PROMs) in patients with and without at least one self-reported allergy undergoing hip arthroscopy were compared. Data on 1434 cases were retrospectively reviewed, and 267 patients were identified with at least one self-reported allergy and randomly matched to a control group on a 1:2 ratio. Four PROMs [Modified Harris Hip Score (mHHS), Hip Outcome Score-Activities of Daily Living (HOS-ADL), Hip Outcome Score-Sports (HOS-Sport) and 33-item International Hip Outcome Tool (iHOT-33)] were collected preoperatively, and at 5–11, 12–23 and 24–35 months postoperatively. Significant PROM differences were found 5–11 months postoperative on mHHS (P < 0.001), HOS-ADL (P = 0.002), HOS-Sport (P < 0.001) and iHOT-33 (P < 0.001). At 12–23 months postoperative, the allergy cohort had significantly worse scores on mHHS (P = 0.002), HOS-ADL (P = 0.001), HOS-Sport (P < 0.001) and iHOT-33 (P < 0.001). They also had significantly worse measures 24–35 months postoperative on mHHS (P = 0.019), HOS-Sport (P = 0.006) and iHOT-33 (P < 0.001). Multivariable logistic regression showed that each additional allergy reported significantly increased the risk of failing to meet the minimal clinically important difference 5–11 months after surgery on mHHS by 1.15 [OR (95% CI): 1.15 (1.03, 1.30), P = 0.014], on HOS-ADL by 1.16 [OR (95% CI): 1.16 (1.02, 1.31), P = 0.021] and on iHOT-33 by 1.20 [OR (95% CI): 1.20 (1.07, 1.36), P = 0.002]. Results suggest self-reported allergies increase the likelihood of a patient-perceived worse outcome after hip arthroscopy. An understanding of this association by the physician is essential during presurgical planning and in the management of postoperative care.

Environmental factors associated with allergy in urban and rural children from the South African Food Allergy (SAFFA) cohort

The recently published South African Food Allergy (SAFFA) study, indicates a clear rural and urban difference in allergy prevalence within a single country.1,2 Various protective and promoting environmental factors have been postulated to influence food and other forms of allergy. Dietary factors, including the consumption of unpasteurized cow’s milk, fermented milk and the variety of foods introduced during infancy were investigated. The influence of fast food, fried food, and microwaved meat and vegetable consumption on allergy were also assessed. This study also investigates the role of a westernized diet, high in advanced glycation end-products (AGE’s), in allergy prevalence. 398 rural and 1185 urban children (12 months to 36 months of age) were screened for self-reported allergic symptoms, food sensitization, and challenge-proven food allergy. Additionally, a subgroup of children (535 urban and 347 rural) was screened for aeroallergen sensitization. Parents/guardians completed questionnaires on antenatal and post-natal environmental and food exposure, including unpasteurized milk and fermented milk products (‘amasi’). 535 urban and 398 rural participants completed questionnaires on fast food consumption. Overall, higher rates of allergic diseases were reported in rural, as supposed to urban children. In the urban cohort, consumption of ‘amasi’ was associated with lower rates of AR (16.8% vs. 31.3%; p<0.001), AD (21.3% vs. 28.6%; p=0.01) and self-reported asthma (5.3% vs. 11.5%; p=0.003). When compared to rural children, consumption of food containing high advanced glycation end products (AGE’s) was associated with significantly higher aeroallergen sensitization rates in urban children (13.8% vs 2.8%; p<0.01, OR 5.5; 1.6-19.1; p<.0.01). In rural children, high consumption of fried/microwaved meat was associated with food sensitization at 1mm and 3mm with odds ratios of 4.4 (CI 1.5-13.0; p=0.01) and 5.0 (CI 1.2-19.9; p=0.02) respectively. Furthermore, high consumption of fruit and vegetables by rural children were associated with significantly higher rates of self-reported asthma (5.7% vs. 3.6%; p<0.001), food sensitization at ≥3mm (8.9% vs. 2.0%; p=0.01) and food allergy (4.4% vs. 0.0%; p<0.001). Early in life, rural exposure protects against some allergies in childhood. Urbanization may hamper exposure to these modifiable, protective elements.

A Potential Role for Epigenetically Mediated Trained Immunity in Food Allergy.

The prevalence of IgE-mediated food allergy is increasing at a rapid pace in many countries. The association of high food allergy rates with Westernized lifestyles suggests the role of gene-environment interactions, potentially underpinned by epigenetic variation, in mediating this process. Recent studies have implicated innate immune system dysfunction in the development and persistence of food allergy. These responses are characterized by increased circulating frequency of innate immune cells and heightened inflammatory responses to bacterial stimulation in food allergic patients. These signatures mirror those described in trained immunity, whereby innate immune cells retain a “memory” of earlier microbial encounters, thus influencing subsequent immune responses. Here, we propose that a robust multi-omics approach that integrates immunological, transcriptomic, and epigenomic datasets, combined with well-phenotyped and longitudinal food allergy cohorts, can inform the potential role of trained immunity in food allergy.

Early Life Domestic Pet Ownership, and the Risk of Pet Sensitization and Atopic Dermatitis in Preschool Children: A Prospective Birth Cohort in Shanghai.

Background: Although domestic pet ownership is on the rise, the impact of early life pet ownership on children's pet sensitization and atopic dermatitis (AD) remains controversial.Methods: Shanghai Allergy Cohort is an ongoing prospective study followed up to the age of 5 years. Pregnant mothers were recruited and their offspring were followed up every year by a group of pediatricians. Information on furred pet ownership was collected by the questionnaire. AD was diagnosed by dermatologists according to disease history and Williams criteria at 5 years ± 1 months. Skin prick test (SPT) was performed to determine sensitization to specific allergens. Multiple logistic regression models were used to evaluate the associations between pet ownership and AD, dog/cat sensitization.Results: In the 538 children at preschool age, 112 (20.82%) were diagnosed with AD. Dermatophagoides pteronyssinus and Dermatophagoides farina were the most common allergens, and almost 10% of children were positive to dog and cat. The percentage of positive SPT reactors at 5-year old was 65.28% in the group of children with AD, higher than that in non-AD group (44.57%). Domestic pet ownership at both infant and preschool period was positively associated with an increased risk of sensitization to dog (OR adjusted = 2.85 [95% CI: 1.08–7.50 for infant exposure], OR adjusted = 2.73 [95% CI: 1.33–5.61] for preschool exposure), and interestingly, pet ownership at infant period negatively associated with higher risk of AD at 5-year old (OR adjusted = 0.33 [95% CI: 0.12–0.88]).Conclusion: This is the first prospective birth cohort study in Shanghai that found half of preschool children had positive allergen sensitization even in the non-AD children. Although early life exposure to dog may increase the risk of dog sensitization, it significantly decreased the risk of AD. The underlying mechanisms warrant further investigations.