Showing papers in "International Archives of Allergy and Immunology in 2020"
TL;DR: The latest insights into the roles of angiotensin-converting enzyme II (ACE2) and Ang II receptor-1 (AT1-R) in this disease are provided and potential targeting of this pathway using JAK inhibitors (JAKinibs) is suggested as a promising approach in patients with COVID-19 who are admitted to hospitals.
Abstract: After the advent of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the outbreak of coronavirus disease 2019 (COVID-19) commenced across the world. Understanding the Immunopathogenesis of COVID-19 is essential for interrupting viral infectivity and preventing aberrant immune responses before a vaccine can be developed. In this review, we provide the latest insights into the roles of angiotensin-converting enzyme II (ACE2) and Ang II receptor-1 (AT1-R) in this disease. Novel therapeutic strategies, including recombinant ACE2, ACE inhibitors, AT1-R blockers, and Ang 1-7 peptides, may prevent or reduce viruses-induced pulmonary, cardiac, and renal injuries. However, more studies are needed to clarify the efficacy of these therapeutics. Furthermore, considering the common role of the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway in AT1-R expressed on peripheral tissues and cytokine receptors on the surface of immune cells, potential targeting of this pathway using JAK inhibitors (JAKinibs) is suggested as a promising approach in patients with COVID-19 who are admitted to hospitals. In addition to antiviral therapy, potential ACE2- and AT1-R-inhibiting strategies, and other supportive care, we suggest other potential JAKinibs and novel anti-inflammatory combination therapies that affect the JAK-STAT pathway in patients with COVID-19. Since the combination of MTX and baricitinib leads to outstanding clinical outcomes, the addition of baricitinib to MTX might be a potential strategy.
147 citations
Humboldt University of Berlin1, Karolinska Institutet2, University of Navarra3, Vrije Universiteit Brussel4, University of Basel5, University of Giessen6, Hannover Medical School7, I.M. Sechenov First Moscow State Medical University8, Ajou University9, Uppsala University10, Heidelberg University11, University of Bern12
TL;DR: An update on chronic urticaria (CU), the expanding spectrum of patient-reported outcome measures (PROMs) for assessing CU disease activity, impact, and control, as well as future treatment options for CU are needed.
Abstract: This update on chronic urticaria (CU) focuses on the prevalence and pathogenesis of chronic spontaneous urticaria (CSU), the expanding spectrum of patient-reported outcome measures (PROMs) for assessing CU disease activity, impact, and control, as well as future treatment options for CU. This update is needed, as several recently reported findings have led to significant advances in these areas. Some of these key discoveries were first presented at past meetings of the Collegium Internationale Allergologicum (CIA). New evidence shows that the prevalence of CSU is geographically heterogeneous, high in all age groups, and increasing. Several recent reports have helped to better characterize two endotypes of CSU: type I autoimmune (or autoallergic) CSU, driven by IgE to autoallergens, and type IIb autoimmune CSU, which is due to mast cell (MC)-targeted autoantibodies. The aim of treatment in CU is complete disease control with absence of signs and symptoms as well as normalization of quality of life (QoL). This is best monitored by the use of an expanding set of PROMs, to which the Angioedema Control Test, the Cholinergic Urticaria Quality of Life Questionnaire, and the Cholinergic Urticaria Activity Score have recently been added. Current treatment approaches for CU under development include drugs that inhibit the effects of signals that drive MC activation and accumulation, drugs that inhibit intracellular pathways of MC activation and degranulation, and drugs that silence MCs by binding to inhibitory receptors. The understanding, knowledge, and management of CU are rapidly increasing. The aim of this review is to provide physicians who treat CU patients with an update on where we stand and where we will go. Many questions and unmet needs remain to be addressed, such as the development of routine diagnostic tests for type I and type IIb autoimmune CSU, the global dissemination and consistent use of PROMs to assess disease activity, impact, and control, and the development of more effective and well-tolerated long-term treatments for all forms of CU.
103 citations
TL;DR: Patients with asthma, especially children, appear to be less susceptible to the coronavirus with a low rate of asthma exacerbations, although recent reports from the USA and the UK suggest that asthma is much more common in children and adults with mild to severe COVID-19.
Abstract: Even though respiratory viruses are one of the most common triggers for asthma exacerbations, not all of these viruses affect patients equally. There is no strong evidence supporting that patients with asthma have a higher risk of becoming seriously ill from coronavirus disease 2019 (CO-VID-19), although recent reports from the USA and the UK suggest that asthma is much more common in children and adults with mild to severe COVID-19 than has previously been reported in Asia and in Europe. As in previous severe acute respiratory syndrome (SARS) outbreaks, patients with asthma, especially children, appear to be less susceptible to the coronavirus with a low rate of asthma exacerbations. A different expression of viral receptors and T2 inflammation can be responsible for different outcomes. Future studies focused on asthma and on other allergic disorders are needed to provide a greater understanding of the impact of underlying asthma and allergic inflammation on COVID-19 susceptibility and disease severity. However, for the moment, it is crucial that asthmatic patients maintain their controller medication, from inhaled corticosteroids to biologics, without making any dose adjustments on their own or stopping the medication. New data are emerging daily, rapidly updating our understanding of this novel coronavirus.
67 citations
TL;DR: Recent literature pointing to important roles for eosinophils in promoting immune defense, antibody production, activation of adipose tissue, and tissue remodeling and fibrosis is reviewed.
Abstract: Eosinophils and their secretory mediators play an important role in the pathogenesis of infectious and inflammatory disorders. Although eosinophils are largely evolutionally conserved, their physiologic functions are not well understood. Given the availability of new eosinophil-targeted depletion therapies, there has been a renewed interest in understanding eosinophil biology as these strategies may result in secondary disorders when applied over long periods of time. Recent data suggest that eosinophils are not only involved in immunological effector functions but also carry out tissue protective and immunoregulatory functions that actively contribute to the maintenance of homeostasis. Prolonged eosinophil depletion may therefore result in the development of secondary disorders. Here, we review recent literature pointing to important roles for eosinophils in promoting immune defense, antibody production, activation of adipose tissue, and tissue remodeling and fibrosis. We also reflect on patient data from clinical trials that feature anti-eosinophil therapeutics.
61 citations
TL;DR: Investigating the role of age, severity, family history, phenotype, and genetic traits may give a better indication into the progression of allergic diseases, and studies following patients from infancy into adulthood and a general increase in longitudinal studies would help broaden the knowledge of allergic disease progression.
Abstract: In recent decades, the worldwide prevalence of allergic disease has increased considerably. The atopic march is a model aimed at explaining the apparent progression of allergic diseases from atopic dermatitis (AD) to allergic asthma (AA) and to allergic rhinitis (AR). It hypothesizes that allergic disease begins, typically in children, with the development of AD, then AA, and finally progresses to AR. This theory has been widely studied in cross-sectional and long-term longitudinal studies and it has been found that as prevalence of AD declines, prevalence of AA increases. A similar relationship is reported between AA and AR. The legitimacy of the atopic march model is, however, currently debated. Epidemiological evidence and criticism of longitudinal studies point to an overstatement of the atopic march's prevalence and incorrect mechanisms, opening a discussion for alternative models to better explain the pathophysiological and epidemiological processes that promote this progression of allergic diseases. Albeit, risk factors for the development and progression of allergic disease, particularly AD, are critical in identifying disease progression. Investigating the role of age, severity, family history, phenotype, and genetic traits may give a better indication into the progression of allergic diseases. In addition, studies following patients from infancy into adulthood and a general increase in longitudinal studies would help broaden the knowledge of allergic disease progression and the atopic march.
50 citations
TL;DR: Commentary on the interplay between the genetic sex and mitochondria and how this may affect a sex-dependent immune response in COVID-19 infection is focused on.
Abstract: The difference between the female and male immune response to COVID-19 infection, and infections in general, is multifactorial The well-known determiners of the immune response, such as X and Y chromosomes, sex hormones, and microbiota, are functionally interconnected and influence each other in shaping the organism's immunity We focus our commentary on the interplay between the genetic sex and mitochondria and how this may affect a sex-dependent immune response in COVID-19 infection Realizing the existence of these interactions may help in designing novel methods or fine-tuning the existing and routine therapies to fight COVID-19 and other infections
43 citations
TL;DR: The aims of this review is to summarize the recent findings on the immunology of this heterogeneous disease and to present the advances in its clinical management.
Abstract: Cutaneous T-cell lymphoma (CTCL) is a heterogeneous disease group of unknown etiology with a complex immunological background. As CTCL arises from T cells that have a vital role in the antitumor response, their therapy is largely aimed at reversing the immunological mechanisms leading to or manifesting during this malignancy. Early disease stages can be controlled with skin-directed therapy in most CTCL cases. Still, advanced CTCL has a dismal prognosis and warrants systemic therapy. Despite considerable progress in understanding the pathophysiology of the disease and the numerous systemic treatment options available, long-term remission rates with conventional treatments alone are still low. Allogeneic hematopoietic stem cell transplantation is currently the only curative option for advanced CTCL, including mycosis fungoides and Sezary syndrome. The aims of this review is to summarize the recent findings on the immunology of this heterogeneous disease and to present the advances in its clinical management.
32 citations
TL;DR: The identification of risk factors, geographical variables, and drugs associated with higher risk for DIA may improve the outcomes of this entity.
Abstract: Drug hypersensitivity is one of the most frequent causes of anaphylaxis, particularly in adults and in hospitalized patients. Drug-induced anaphylaxis (DIA) is also associated with more severe outcomes than other anaphylaxis triggers, and drugs are responsible for the majority of deaths due to anaphylaxis. We here review the current knowledge on the incidence, prevalence, drugs involved, mortality, and mortality risk factors for DIA. The incidence of both anaphylaxis and DIA seems to be increasing worldwide. Antibiotics and analgesics are the most frequently reported triggers of DIA. However, the importance of other drug groups should be taken into account, especially in particular settings (e.g., peri-operative and oncology). The identification of risk factors, geographical variables, and drugs associated with higher risk for DIA may improve the outcomes of this entity.
27 citations
TL;DR: While SCIT and SLIT have similar rates of clinical improvement, the 2 modes reveal heterogeneous changes of CD4+CD25+Foxp3+ Tregs, sIgG4 and cytokines.
Abstract: BACKGROUND Few studies have directly compared the immunologic responses to specific subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT). OBJECTIVE We aimed to directly compare clinical efficacy and immunological responses between SLIT and SCIT in allergic rhinitis (AR) sensitized to house dust mites. METHODS Sixty-seven patients (age 5-55 years) with moderate-severe Dermatophagoides pteronyssinus (Der-p) and Dermatophagoides farinae AR with or without asthma were randomized (2:2:1) into SLIT (n = 27), SCIT (n = 26) and placebo (n = 14) groups. Symptom and medication scores, visual analogue score, serum Der-p specific immunoglobulin G4 (Der-p-sIgG4), CD4+CD25+FoxP3+ regulatory T cells (Tregs) and serum cytokines were measured. RESULTS After 1-year treatment, a significant improvement of total rhinitis score (TRS), total rhinitis medication score (TRMS) and visual analogue score occurred in both SLIT and SCIT. There were no differences in clinical efficacy except for TRMS (p = 0.026) when SLIT and SCIT were directly compared. CD4+CD25+FoxP3+ Tregs had a trend towards upregulation in the 2 modes and inversely correlated with TRS (p = 0.024) only in SLIT. Der-p-sIgG4 significantly increased in SLIT and SCIT (p < 0.05), and it was 30 times higher in SCIT than SLIT after the treatment (p < 0.05). Serum interferon-γ significantly increased only in SCIT after 1 (p = 0.008), 6 (p = 0.007) and 12 (p = 0.008) months of treatment and inversely correlated with TRS (p = 0.032). CONCLUSION While SCIT and SLIT have similar rates of clinical improvement, the 2 modes reveal heterogeneous changes of CD4+CD25+Foxp3+ Tregs, sIgG4 and cytokines.
26 citations
TL;DR: A better understanding of the molecular mechanisms involved in the mode of action of specific cannabinoids and cannabinoid receptors on relevant immune cells under different biological contexts might well contribute to the design of novel strategies for the prevention and treatment of allergic diseases.
Abstract: The human endocannabinoid system (ECS) is a complex signalling network involved in many key physiological processes. The ECS includes the cannabinoid receptors, the endocannabinoid ligands, and the enzymes related to their synthesis and degradation. Other cannabinoids encompass the phytocannabinoids from Cannabis sativaL.(marijuana) and the synthetic cannabinoids. Alterations in the ECS are associated with different diseases, including inflammatory and immune-mediated disorders such as allergy. Allergy is a global health problem of increasing prevalence with high socio-economic impact. Different studies have convincingly demonstrated that cannabinoids play a role in allergy, but their actual contribution is still controversial. It has been shown that cannabinoids exert anti-inflammatory properties in the airways and the skin of allergic patients. Other studies reported that cannabinoids might exacerbate asthma and atopic dermatitis mainly depending on CB2-mediated signalling pathways. A better understanding of the molecular mechanisms involved in the mode of action of specific cannabinoids and cannabinoid receptors on relevant immune cells under different biological contexts might well contribute to the design of novel strategies for the prevention and treatment of allergic diseases. Future research in this promising emerging field in the context of allergy is warranted for the upcoming years.
23 citations
TL;DR: MiR-204-5p inhibits TGF-β1-induced proliferation and ECM production of airway smooth muscle cells by regulating Six1, identifying a potential therapeutic target for preventing airway remodeling in asthma.
Abstract: Background Transforming growth factor-β1 (TGF-β1)-in-duced proliferation of airway smooth muscle cells plays critical roles in the development of airway remodeling. Six1 (sine oculis homeobox homolog 1) has been demonstrated to be involved in airway inflammation and remodeling in asthmatic mice. Objectives The aim of this work was to investigate the potential role of miR-204-5p in the proliferation and extracellular matrix (ECM) production of airway smooth muscle cells in asthma. Methods Real-time PCR was used to measure the expression of miR-204-5p in asthmatic airway smooth muscle cells. Cell viability and apoptosis were detected to evaluate the effect of miR-204-5p on airway smooth muscle cells. Dual-luciferase reporter experiments were applied to identify the target genes of miR-204-5p. Results MiR-204-5p was downregulated notably in asthmatic airway smooth muscle cells as well as cells stimulated with TGF-β1. Overexpression of miR-204-5p markedly suppressed the TGF-β1-induced proliferation of airway smooth muscle cells and the deposition of ECM, whereas the inhibition of miR-204-5p significantly enhanced the proliferation of airway smooth muscle cells and upregulated the level of fibronectin and collagen III. Furthermore, subsequent analyses demonstrated that Six1 was a direct target of miR-204-5p, and Western blot further indicated that miR-204-5p negatively regulated the expression of Six1. Most importantly, the restoration of Six1 expression reversed the inhibitory effect of miR-204-5p on TGF-β1-induced proliferation and ECM production. Conclusions MiR-204-5p inhibits TGF-β1-in-duced proliferation and ECM production of airway smooth muscle cells by regulating Six1, identifying a potential therapeutic target for preventing airway remodeling in asthma.
TL;DR: The anticipated characteristics of a COVID-19 vaccine are reviewed to avoid vaccine-associated eosinophil immunopathology and there is a concern regarding both vaccine-induced eOSinophilic lung disease and eos inophil-associated Th2 immunopotentiation following infection after vaccination.
Abstract: A vaccine to protect against COVID-19 is urgently needed. Such a vaccine should efficiently induce high-affinity neutralizing antibodies which neutralize SARS-CoV-2, the cause of COVID-19. However, there is a concern regarding both vaccine-induced eosinophilic lung disease and eosinophil-associated Th2 immunopotentiation following infection after vaccination. Here, we review the anticipated characteristics of a COVID-19 vaccine to avoid vaccine-associated eosinophil immunopathology.
TL;DR: A significant rise in the total number of weed pollen sensitization as well as increases in polysensitization, predominantly in younger patients is demonstrated over the last 20 years.
Abstract: Background In contrast to the 3 major aeroallergens tree pollen, grass pollen, and house dust mites, allergic rhinitis caused by herbal pollen has received comparatively little attention in recent clinical studies. Since various weeds flower during summer until fall, allergic rhinitis to weeds may be underdiagnosed and/or mistakenly diagnosed as grass pollen allergy. Objective To investigate (i) the currently most frequent weed allergy between mugwort, ragweed, plantain, chamomile, nettle, and oilseed rape and (ii) time trends in prevalence of sensitization to weed pollen in the middle of Germany over the last 20 years. Methods This study, the largest of its kind to date, monocentrically evaluated the prick test results of a total of 6,220 patients with suspected RCA over a period of 20 years (1998-2017). Results In the study cohort, sensitization rates to plantain almost doubled from 26.6% in the decade 1998-2007 to 50.5% in 2008-2017. Identical increases were observed for ragweed, while sensitization rates for mugwort stayed largely unchanged. The most prominent increase in positive skin prick tests to plantain and ragweed pollen was mainly observed in younger patients. Further, we identified a trend toward polysensitization, currently dominated by plantain and ragweed. Sensitization to weed pollen was found to be highly associated with additional sensitizations to grass and/or birch pollen. Conclusion Plantain is currently the best choice to screen rhinitis patients for weed allergy which identifies 86% of all weed-sensitized individuals, at least in Germany. Over the last 20 years, we demonstrate a significant rise in the total number of weed pollen sensitization as well as increases in polysensitization, predominantly in younger patients.
TL;DR: Although severe and early-onset AD is a predictor of the presence and magnitude of FA in infancy, the spectrum of FA is a reflection of cultural characteristics and may be an expression of the extent of the immune dysregulation underlying atopy and allergy.
Abstract: OBJECTIVE Precise diagnosis of allergy requires knowledge of the population's food allergy (FA) spectrum and predictors. METHODS Medical charts of Turkish children aged 0-2 years with FA and/or atopic dermatitis (AD) were reviewed. RESULTS A total of 1,389 patients, 912 with FA and 1,140 with AD, were included. In the FA group, the most frequently diagnosed FAs were egg white (75.9%), cow's milk (55.7%), tree nuts (31.5%) and sesame (20.6%). The detection of FA in 99% of children with any kind of FA necessitate testing with egg white, cow's milk, hazelnut, sesame, walnut, cashew, and pistachio. In the FA group, 72.7 and 56.8% had AD and multiple FA respectively. Multiple FA (56.8 vs. 49.8%) and hen's egg allergy (85.5 vs. 50.2%, p < 0.005) were more common and cow's milk allergy (51.4 vs. 67.1%, p < 0.005) less common in the AD subgroup of the FA group than in the non-AD subgroup. Multiple FA likelihood increases parallel to the severity of AD (p < 0.05). In the AD group, 58.2% had an immunoglobulin E-mediated FA. The risk of concomitant FA increased as the age at symptom onset of AD decreased (OR 0.800 [95% CI 0.731-0.875]; p < 0.001) and the severity of AD increased (OR 2.350 [95% CI 1.898-2.911]; p < 0.001). CONCLUSION Although severe and early-onset AD is a predictor of the presence and magnitude of FA in infancy, the spectrum of FA is a reflection of cultural characteristics. The clinical presentations of both AD and FA may in fact be an expression of the extent of the immune dysregulation underlying atopy and allergy.
TL;DR: The structural characteristics, expression patterns, and biological characteristics of IL-17D along with its potential function in the pathogenesis of disease are introduced.
Abstract: The interleukin-17 (IL-17) family is a relatively new family of cytokines consisting of 6 related factors (IL-17A-IL-17F), while the receptor family consists of 5 members: IL-17RA-IL-17RE. IL-17A is the prototype member of this family, which is also the signature cytokine of T helper 17 (Th17) cells. Th17 cells are involved in the development of autoimmune disease, inflammation, and tumors. Although IL-17D is similar to IL-17A in its ability to induce inflammatory cytokine production, there are fewer studies on IL-17D. Recently, the role of IL-17D in tumors and infections has attracted our attention. Some knowledge of function of IL-17D has been gained by studies using nonmammalian species. In this review, we introduce the structural characteristics, expression patterns, and biological characteristics of IL-17D along with its potential function in the pathogenesis of disease.
TL;DR: Alpha-gal sIgE is a sensitive marker in the diagnosis of alpha-gal syndrome but has limited predictive value for the characteristics or severity of this allergy.
Abstract: Background Alpha-gal syndrome is a complex allergy with high clinical relevance regarding mammalian-derived food and drugs and is characterized by the presence of IgE antibodies directed at the carbohydrate galactose-α-1,3-galactose. As not all alpha-gal sIgE-positive individuals pre-sent clinical symptoms upon consumption of mammalian meat, the diagnostic value of alpha-gal sIgE has yet to be clarified. Objective To investigate the prevalence of alpha-gal-sIgE positivity among allergy patients, examine the impact of tick bites as associated risk factors and determine the diagnostic value of alpha-gal-sIgE positivity. Methods A retrospective cross-sectional study evaluating patients in the Allergy Unit was performed. Alpha-gal-sIgE levels were assessed by ImmunoCAP assay. Exposure to tick bites was assessed by a questionnaire. A receiver operating characteristics (ROC) curve analysis was performed to determine the diagnostic value of alpha-gal sIgE for the diagnosis of alpha-gal syndrome. Results In the study population (n = 1369), the overall prevalence of alpha-gal-sIgE-positive (≥0.10 kUA/L) individuals was 19.9%, and the highest prevalence (30.2%) was found in patients with insect venom allergies. A reported tick bite within the 12 months prior to blood sampling significantly increased the risk of alpha-gal-sIgE positivity (OR 2.084). The ROC curve analysis indicated alpha-gal sIgE ≥0.54 kUA/L as the optimal cutoff point for assessing the diagnostic value of alpha-gal syndrome in allergy patients. Conclusions In allergy care settings, alpha-gal-sIgE positivity is a common finding. Alpha-gal sIgE is a sensitive marker in the diagnosis of alpha-gal syndrome but has limited predictive value for the characteristics or severity of this allergy.
TL;DR: This study suggests that mepolizumab is effective in improving control of asthma, lung function parameters, exhaled biomarkers, and nasal symptoms in patients with severe eosinophilic asthma.
Abstract: Introduction Interleukin-5 (IL-5) is the principal cytokine regulating eosinophil growth, differentiation, activation, and expression. It is a specific target of mepolizumab, an anti-IL-5 monoclonal antibody used in the treatment of severe eosinophilic asthma. This new drug can improve symptoms, reduce asthma exacerbations and steroid use. Few data are available on its efficacy for nasal symptoms. Objective To describe the all-round clinical impact of mepolizumab in a real-life setting, evaluating the efficacy and safety of the drug in severe eosinophilic asthma patients. Population and methods We retrospectively collected the clinical and functional data on 27 patients (16 males) affected with severe eosinophilic asthma, diagnosed at the Siena Regional Referral Centre and monitored for 6 months. Clinical, immunological, and functional data at baseline and follow-up were entered in a database together with comorbidities, number of exacerbations, steroid treatment, multiple-flow exhaled nitric oxide, and validated questionnaires. Results A significant reduction in asthma exacerbations was observed in all patients after 6 months of the biological therapy (p = 0.0009), and 4/6 patients discontinued chronic oral steroids. A significant improvement in ACT, FEV1, SNOT22, and alveolar nitric oxide was observed after 1 month of mepolizumab (p = 0.003, p = 0.007, p = 0.047, and p = 0.019, respectively) and maintained after 6 months of treatment. After 6 months, FeNO 50 was reduced as well (p = 0.030). Mepolizumab was very well tolerated, and no major side effects were observed. Conclusions Our study suggests that mepolizumab is effective in improving control of asthma, lung function parameters, exhaled biomarkers, and nasal symptoms in patients with severe eosinophilic asthma.
TL;DR: Results indicate that besides eosinophils, KL-6 and sL-selectin are useful as biomarkers of early response that can also involve in the pathogenesis of severe asthma.
Abstract: Background New anti-IL-5 antibodies, mepolizumab and benralizumab, have recently been approved for severe asthma, sharing the same inclusion criteria. Objective To contribute on biomarkers research leading to the personalized choice, we investigated L-selectin, Krebs von den Lungen (KL-6), and lymphocyte subsets as bioindicators of airway hyper-responsiveness and remodeling. Materials and methods A cohort of 28 patients affected by severe eosinophilic asthma were treated with anti-IL-5 drugs. According to clinical parameters, patients were subdivided into early and partial responders. Lymphocytes subsets were analyzed through flow cytometry, while KL-6 and sL-selectin were analyzed on serum samples. Clinical, functional, and immunological data at baseline (T0), after 1 month (T1), and 6 months of therapy were collected in a database. Results All treated patients showed an increase in the percentage of forced expiratory volume in the first second (FEV1) and FEV1/forced vital capacity ratio and a decrease of peripheral eosinophils for both drugs after 1 month of treatment. Mepolizumab-treated patients also showed decreased CD8+ and NKT-like cell percentages and a significant increase in sL-selectin concentrations between T0 and T1. Stratifying the cohort of our patients in early and partial responders at T0, they showed a reduction of peripheral eosinophils, sL-selectin and KL-6, while no differences were found at T0 between early and partial responders patients treated with benralizumab. Conclusions This real-life study provides new insights for the personalized approach to severe asthma therapy. Although preliminary, the results indicate that besides eosinophils, KL-6 and sL-selectin are useful as biomarkers of early response that can also involve in the pathogenesis of severe asthma.
TL;DR: Treatment with omalizumab was effective and safe in patients with ABPA, regardless of comorbid chronic respiratory tract infections.
Abstract: Background Allergic bronchopulmonary aspergillosis (ABPA) develops in the presence of predisposing conditions such as asthma and cystic fibrosis. Even ABPA accompanied by asthma is often complicated by chronic Pseudomonas aeruginosa or nontuberculous mycobacterial infection of the lower respiratory tract, rendering treatment with corticosteroids difficult. There have been several reports on the effectiveness of omalizumab, an anti-IgE antibody, in patients with ABPA. We analyzed the effectiveness and adverse effects of omalizumab in ABPA patients with chronic respiratory infections. Methods Using our nationwide survey database and published case reports, we identified patients with severe asthma and ABPA who fulfilled the International Society for Human and Animal Mycology criteria and who had been treated with omalizumab. Exacerbation rates, control of symptoms, doses of oral corticosteroids, and pulmonary function were evaluated. Results Among 25 patients with ABPA treated with omalizumab (median age 62 years, range 33-83 years), 12 patients had a chronic bacterial infection of the lower airways attributable to P. aeruginosa (n = 6) or nontuberculous mycobacteria (n = 6) at the initiation of omaliz-umab. Treatment with omalizumab reduced the frequency of exacerbations and systemic corticosteroid doses and improved pulmonary function. There were no significant adverse events or worsening of infection during treatment with omalizumab, except for injection-site reactions. Conclusions Treatment with omalizumab was effective and safe in patients with ABPA, regardless of comorbid chronic respiratory tract infections.
TL;DR: In patients with severe eosinophilic asthma, 1 year of treatment with mepolizumab was safe, resulted in significant reduction of the annual exacerbation rate, reduction (or even discontinuation) of the needed dose of OCS, and improvements of asthma control and lung function.
Abstract: Introduction Mepolizumab is a monoclonal antibody against IL-5 for the treatment of severe eosinophilic asthma. The aim of the current study was to present a predesigned interim analysis of the data of patients who have completed 1 year of therapy with mepolizumab. Methods This study is a prospective multicenter, noninterventional 2-year observational study and aims to describe the clinical benefit and safety profile of mepolizumab in patients with severe eosinophilic asthma. Results Compared to the year preceding the initiation of treatment, the annual rate of exacerbations decreased significantly, from 4.3 ± 2.3 to 1.3 ± 1.8; p Conclusions We have shown that in patients with severe eosinophilic asthma, 1 year of treatment with mepolizumab was safe, resulted in significant reduction of the annual exacerbation rate, reduction (or even discontinuation) of the needed dose of OCS, and improvements of asthma control and lung function.
TL;DR: It is shown in peanut-allergic mice that a single high-affinity mAb specific for Ara h 2 is able to block systemic and local allergic reactions induced by the complex peanut extract, and in vivo that protection was dependent on FcγRIIb.
Abstract: Background: peanut allergy is the most prevalent and dangerous food allergy. Peanuts consist of a large number of different allergens and peanut-allergic patients are frequently sensitized to multiple allergens. Hence, conventional de-sensitization approaches aim at targeting as many allergens as possible. Methods: the monoclonal anti-Ara h 2 antibody (mAb) was produced by hybridoma cells derived from WT BALB/c mice after immunization with a vaccine based on Virus-Like-Particles coupled to Ara h 2. BALB/c mice were sensitized intraperitoneally with peanut extract absorbed to Alum and mAbs were applied i.v.. Challenge was performed the next day with the whole peanut extract intravenously and via skin prick test. Results: here we show in peanut-allergic mice that a single high-affinity monoclonal antibody specific for Ara h 2 is able to block systemic and local allergic reactions induced by the complex peanut extract. We confirm in vitro binding of the mAb to the inhibitory low-affinity FcRIIb receptor using a sensitive biosensor and demonstrate in vivo that protection was dependent on FcRIIb. Conclusion: a single mAb specific for Ara h 2 is able to improve local and systemic allergic symptoms induced by the whole allergen mixture.
TL;DR: The results suggest that CM- and egg-specific IgE levels at the first reaction are the most significant prognostic factors in predicting acquisition of oral tolerance.
Abstract: Background: Most of children with cow’s milk (CM) and hen’s egg allergies are known to outgrow their diseases with time, but recent studies have demonstrated that children tend to continue to have allergic symptoms in adolescence and adulthood. The aim of this study was to investigate the natural course of CM and egg allergies in Korean children and analyze prognostic factors. Methods: In this retrospective study, we reviewed data of children with CM allergy and with egg allergy using medical records and parental telephone interviews. Diagnosis of CM or egg allergy was based on positive oral food challenge test or convincing history of allergic symptoms in combination with positive allergen-specific IgE. Acquisition of tolerance was defined by the absence of allergic symptoms after reintroduction of the offending foods. Results: Half of the children outgrew CM allergy at a median age of 8.7 years. CM-specific IgE level at the first reaction was a significant prognostic factor for oral tolerance in CM allergy (p < 0.05). The median age to acquire oral tolerance in 50% of patients with egg allergy was 5.6 years. Egg-specific IgE level at the first reaction and family history of allergic diseases significantly affected the prognosis in children with egg allergy (p < 0.05). Conclusions: Half of Korean children with CM and egg allergies had symptom resolution at 8.7 and 5.6 years of age, respectively. Our results also suggest that CM- and egg-specific IgE levels at the first reaction are the most significant prognostic factors in predicting acquisition of oral tolerance.
TL;DR: The systematic review suggests that EPIT might induce desensitization in peanut allergy and an increased risk of local AEs, and should be interpreted with caution owing to the limited study and heterogeneity.
Abstract: Objectives: To systematically review the effect and safety of epicutaneous immunotherapy (EPIT) for allergic diseases. Methods: We searched PubMed, EMBASE, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, CQ VIP Database, Wanfang Data, and international trial register from their inception to July 29, 2019, without language restrictions, for randomized controlled trials (RCTs) that compared EPIT versus no EPIT for allergen-triggered allergic reactions. We assessed certainty of evidence by the GRADE approach. Results: Ten RCTs with 1,085 participants (aged from 10 months to 65 years) comparing EPIT with placebo for peanut, cow milk, or grass-pollen allergy met the eligibility criteria. A substantial benefit in terms of desensitization in EPIT group was more likely for peanut or cow milk protein allergy (risk ratio [RR] 2.34, 95% CI 1.69–3.23; I2 = 0%; high certainty evidence). EPIT increased local-treatment-related adverse events (L-TRAE; RR 1.56, 95% CI 1.03–2.36; I2 = 82%; moderate certainty evidence). But there were no significantly increased risk of any TRAEs (low certainty evidence) or systemic-TRAEs (S-TRAEs; very low certainty evidence) in EPIT group. The incidence rate of serious AEs, the use of rescue medications, and anaphylactic reactions stratified by organ systems including skin and mucosa, eyes and upper respiratory, lower respiratory, and gastrointestinal system in EPIT group were similar to placebo group. In subgroup analysis, desensitization of EPIT was significantly effective in peanut allergy (RR 2.29, 95% CI 1.64–3.21; I2 = 0%) and children <12 years (RR 2.85, 95% CI 1.92–4.24; I2 = 0%) with high certainty evidence. Only epicutaneous grass-pollen immunotherapy significantly increased the risk of S-TRAE (RR 4.65, 95% CI 1.10–19.64; I2 = 0%). Conclusion: The systematic review suggests that EPIT might induce desensitization in peanut allergy and an increased risk of local AEs. These findings should be interpreted with caution owing to the limited study and heterogeneity. More data in the older (children ≥12 years and adults) and other allergic diseases are needed.
TL;DR: Accelerated VIT protocols, namely, rush and ultra-rush protocols are safe therapeutic options for Hymenoptera venom-allergic patients and displayed fewer SR than cluster V IT protocols in this study.
Abstract: INTRODUCTION Venom immunotherapy (VIT) is highly effective and the treatment of choice for patients with a history of systemic anaphylactic reactions to a Hymenoptera sting. It has been assumed that VIT protocols with a rapid dose increase during the induction phase are associated with a higher frequency of systemic reactions (SR); however, study data addressing this issue are conflicting. OBJECTIVE The aim of this study was to compare the safety of 3 different Hymenoptera VIT protocols (half-day ultra-rush, 3-day rush, 3-week cluster). METHODS This retrospective 2-center study included 143 Hymenoptera venom-allergic patients, who underwent 147 VIT procedures during the years 2015-2018. Twenty cluster, 75 rush, and 52 ultra-rush VIT protocols were performed with honeybee (54 protocols) and wasp (93 protocols) venom. All documented side effects were classified into large local and SR (Ring and Messmer classification). RESULTS SR were observed during 11 (7.5%) VIT procedures and did not exceed severity grade II. SR occurred more frequently in cluster compared to accelerated protocols. This result was observed for both honeybee (cluster: 25%, rush: 8.7%, and ultra-rush: 15.8%) and wasp VIT (cluster: 12.5%, rush: 0%, and ultra-rush: 6.1%), though the differences were statistically significant only in the wasp VIT subgroup. Honeybee venom elicited more SR than wasp venom (14.8 and 3.2%, respectively, p = 0.01). The risk for SR did not depend on age, sex, concomitant antihypertensive medication, hypertryptasemia, or severity of the index sting reaction. CONCLUSION Accelerated VIT protocols, namely, rush and ultra-rush protocols are safe therapeutic options for Hymenoptera venom-allergic patients and displayed fewer SR than cluster VIT protocols in our study.
TL;DR: A comprehensive, updated summary on the variety of non-anaphylactic conditions where hypertryptasemia may be seen and the practicing clinician ought to be aware of these important differential diagnoses.
Abstract: One of the most important blood tests in the field of allergy, mast cell tryptase has numerous diagnostic uses, particularly for anaphylactic reactions and for the diagnosis of mastocytosis. However, there are numerous other non-anaphylactic conditions where clinicians may see elevated serum tryptase (hypertryptasemia) and the practicing clinician ought to be aware of these important differential diagnoses. Such conditions include systemic mastocytosis, hematological malignancies, and chronic kidney disease. This article provides a comprehensive, updated summary on the variety of non-anaphylactic conditions where hypertryptasemia may be seen.
TL;DR: A meta-analysis of relationships between IL-8, IL-10, or IL-18 polymorphisms and predisposition of IBD by merging the results of eligible literatures shows thatIL-8 rs4073,IL-10 rs1800871, ILs1800872, IL,10 rs1800896, andIL-18 rs1946518 polymorphism may influence predispositionof IBD.
Abstract: BACKGROUND Whether interleukin (IL)-8, IL-10, and IL-18 polymorphisms influence predisposition of inflammatory bowel disease (IBD) remains uncertain. OBJECTIVES The authors conducted a meta-analysis to explore relationships between IL-8, IL-10, or IL-18 polymorphisms and predisposition of IBD by merging the results of eligible literatures. METHODS A thorough literature search in MEDLINE, Embase, Wanfang, VIP, and CNKI was conducted by the authors to identify eligible literatures, and 33 literatures were finally selected for merged analyses. RESULTS We found that genotypic frequencies of IL-8 rs4073, IL-10 rs1800871, IL-10 rs1800872, and IL-10 rs1800896 polymorphisms among cases with IBD and population-based controls differed significantly. Moreover, we found that genotypic frequencies of IL-8 rs4073, IL-10 rs1800871, and IL-18 rs1946518 polymorphisms among cases with IBD and population-based controls of Asian origin differed significantly, whereas genotypic frequency of IL-10 rs1800896 polymorphism among cases with IBD and population-based controls of Caucasian origin also differed significantly. Furthermore, genotypic frequency of IL-18 rs187238 polymorphism among cases with Crohn's disease (CD) and population-based controls also differed significantly. CONCLUSIONS The present meta-analysis shows that IL-8 rs4073, IL-10 rs1800871, IL-10 rs1800872, IL-10 rs1800896, and IL-18 rs1946518 polymorphisms may influence predisposition of IBD. Furthermore, IL-18 rs187238 polymorphism may influence predisposition of CD, but not predisposition of ulcerative colitis.
TL;DR: Specific abnormalities in B- and T-lymphocyte compartments were identified in pediatric-onset CVID patients and appear to be associated with end organ manifestations.
Abstract: INTRODUCTION Common variable immunodeficiency (CVID) is characterized by recurrent infections, autoimmunity, lymphoproliferation, hypogammaglobulinemia, and defective antibody production. In CVID, B-cell abnormalities were described to predict end organ involvement and prognosis. Pediatric-onset CVID is much rarer than adult CVID, and lymphocyte subset abnormalities have not been thoroughly evaluated. OBJECTIVE We sought to determine lymphocyte subset abnormalities and their association with end organ involvement in pediatric-onset CVID patients. METHODS The clinical manifestations and laboratory findings including absolute numbers and percentages of B-, T-, and NK cell populations were assessed in pediatric-onset CVID patients and compared to age-matched healthy controls. The patients were divided into 2 groups according to age at assessment (pediatric CVID patients: 10-16 years, n = 9; and adult CVID patients: >16 years, n = 13). The comparisons between lymphocyte subsets and organ involvement were also evaluated. RESULTS Mean age at symptom onset was 18 (3-204) months. All CVID patients with pediatric onset had decreased levels of total and memory B cells, CD4+ T cells, CD4+CD45RA+ naive T cells, and recent thymic emigrant (RTE) cells. On the other hand, they had increases in CD8+CD45RO+ memory T cells. Interestingly, adult CVID patients demonstrated high frequencies of activated and double-negative T cells, which were unique only for this group of patients. Specific cellular abnormalities associated with the reduction in B and NK cells and increase in CD8+ T cells were found in patients with bronchiectasis. Moreover, in pediatric CVID patients, low serum IgA levels and decreased numbers of naive T and RTE cells were determined as risk factors for chronic diarrhea. CONCLUSIONS Specific abnormalities in B- and T-lymphocyte compartments were identified in pediatric-onset CVID patients and appear to be associated with end organ manifestations.
TL;DR: The potential role of the gut mycobiome and the extent to which this is relevant to fungal allergy, diagnosis and human health is discussed, as well as the aetiology and pathogenies of these diseases, particularly the neglected fungal allergic diseases.
Abstract: The prevalence of allergic diseases in the African continent has received limited attention with the allergic diseases due to fungal allergens being among the least studied. This lead to the opinion being that the prevalence of allergic disease is low in Africa. Recent reports from different African countries indicate that this is not the case as allergic conditions are common and some; particularly those due to fungal allergens are increasing in prevalence. Thus, there is need to understand both the aetiology and pathogenies of these diseases, particularly the neglected fungal allergic diseases. This review addresses currently available knowledge of fungal-induced allergy, disease pathogenesis comparing findings from human versus experimental mouse studies of fungal allergy. The review discusses the potential role of the gut mycobiome and the extent to which this is relevant to fungal allergy, diagnosis and human health.
TL;DR: HIF1α deficiency in dendritic cells attenuates symptoms and inflammatory indicators of allergic rhinitis in a SIRT1-dependent manner.
Abstract: Background Allergic rhinitis is the most prevalent atopic disorder worldwide. Inflammation is believed to participate in allergic rhinitis. Previous studies indicate that hypoxia-inducible factor (HIF) promotes the development of allergic rhinitis, and dendritic cells are also involved in allergic rhinitis. Methods We explored the consequences of HIF1α deficiency in dendritic cells on allergic rhinitis. Allergic rhinitis in mice was induced by ovalbumin (OVA). The levels of IgE, leukotriene C4 (LTC4), eosinophil cationic protein (ECP), prostaglandin D2 (PGD2), IFN-γ, IL-2, IL-4, IL-5, IL-10, and IL-13 in serum or nasal lavage fluid (NLF) were detected by ELISA. Inflammatory cells in NLF were counted by hemocytometer. The protein levels of p-ERK1/2, p-p38, p-JNK2, SIRT1, p-IκBα, and p65 were determined by Western blot. Results HIF1α deficiency in dendritic cells (HIF1αCD11c-/-) decreased sneezing and nasal rubbing, the production of OVA-specific IgE, LTC4, and ECP in serum and NLF, and the numbers of leukocytes, eosinophils, lymphocytes, and neutrophils in NLF. Th1 cytokines increased, while Th2 cytokines decreased in HIF1aCD11c-/- mice. SIRT1/NF-κB signaling was inhibited in HIF1αCD11c-/- mice, while SIRT1 inhibitor administration in HIF1αCD11c-/- mice attenuated the symptoms and inflammatory indicators of allergic rhinitis. Conclusion HIF1α deficiency in dendritic cells attenuates symptoms and inflammatory indicators of allergic rhinitis in a SIRT1-dependent manner.
TL;DR: The allergy-related comorbidities of IBS are presented, including genetic, environmental, and immunologic factors, followed by potential implications in the screening and treatment of allergies in IBS patients.
Abstract: Irritable bowel syndrome (IBS) is a functional gastrointestinal disease and the most common cause of prolonged abdominal pain and bowel disturbances in the developed world. While initially thought to be functional or psychosomatic in nature, IBS is now recognized as a heterogeneous group of conditions. A subset of IBS patients and patients with allergic diseases share some characteristic inflammatory features. In fact, atopic children show an increased likelihood of developing IBS as adults. Given these findings, a subset of IBS may be suffering from allergy-related gut diseases. In this review, we present the allergy-related comorbidities of IBS, including genetic, environmental, and immunologic factors. We discuss studies demonstrating an increased sensitization of IBS patients to aeroallergens compared to food allergens. We then postulate potential pathophysiological mechanisms underlying both IBS and aeroallergens in the gut, followed by potential implications in the screening and treatment of allergies in IBS patients.