Basophil Histamine Release Assay Research Articles

Detection of Sensitization Profiles with Cellular In Vitro Tests in Wheat Allergy Dependent on Augmentation Factors (WALDA).

Wheat allergy dependent on augmentation factors (WALDA) is the most common gluten allergy in adults. IgE-mediated sensitizations are directed towards ω5-gliadin but also to other wheat allergens. The value of the different in vitro cellular tests, namely the basophil activation test (BAT) and the active (aBHRA) and passive basophil histamine-release assays (pBHRA), in the detection of sensitization profiles beyond ω5-gliadin has not been compared. Therefore, 13 patients with challenge-confirmed, ω5-gliadin-positive WALDA and 11 healthy controls were enrolled. Specific IgE (sIgE), skin prick tests, BATs, aBHRA, and pBHRA were performed with allergen test solutions derived from wheat and other cereals, and results were analyzed and compared. This study reveals a distinct and highly individual reactivity of ω5-gliadin-positive WALDA patients to a range of wheat allergens beyond ω5-gliadin in cellular in vitro tests and SPT. In the BAT, for all tested allergens (gluten, high-molecular-weight glutenin subunits, α-amylase/trypsin inhibitors (ATIs), alcohol-free wheat beer, hydrolyzed wheat proteins (HWPs), rye gluten and secalins), basophil activation in patients was significantly higher than in controls (p = 0.004-p < 0.001). Similarly, significant histamine release was detected in the aBHRA for all test substances, exceeding the cut-off of 10 ng/mL in all tested allergens in 50% of patients. The dependency of tests on sIgE levels against ω5-gliadin differed; in the pBHRA, histamine release to any test substances could only be detected in patients with sIgE against ω5-gliadin ≥ 7.7 kU/L, whereas aBHRA also showed high reactivity in less sensitized patients. In most patients, reactivity to HWPs, ATIs, and rye allergens was observed. Additionally, alcohol-free wheat beer was first described as a promising test substance in ω5-gliadin-positive WALDA. Thus, BAT and aBHRA are valuable tools for the identification of sensitization profiles in WALDA.

Circulating basophils in patients with type IIb autoimmune chronic spontaneous urticaria have a lower histamine content

AbstractBackgroundPatients suffering from chronic spontaneous urticaria (CSU) are typically classified as type I or type IIb autoimmune CSU, but further patient stratification is hindered by the lack of biomarkers.ObjectivesWe investigated whether the histamine content of individual basophils differ between patient subtypes in CSU to evaluate its potential as a biomarker.MethodsA total of 101 patients diagnosed with CSU were included in the study. The histamine content per circulating basophil was derived from the basophil count in peripheral blood and levels of total cellular blood histamine. These measures, together with results from the serum‐induced basophil histamine release assay (s‐BHRA), were correlated to information on demographics, clinical characteristics, patient reported outcomes and laboratory analyses.ResultsThe histamine content per basophil was significantly different between s‐BHRA positive and ‐negative patients (0.175 vs. 1.40 pg/cell, p &lt; 0.001) and showed a significant negative correlation to the degree of basophil activation in s‐BHRA (ρ = −0.209, p = 0.036). Furthermore, the amount of histamine in individual basophils was found to be significantly correlated with levels of total cellular blood histamine (ρ = 0.376, p &lt; 0.001), eosinophil counts (ρ = 0.205, p = 0.040), levels of thyroid stimulating hormone (ρ = −0.246, p = 0.014) and titre of antibodies against thyroid peroxidase (ρ = −0.216, p = 0.031) and thyroglobulin (ρ = −0.203, p = 0.044).ConclusionsLow content of intracellular histamine in circulating basophils is associated with known markers of type IIb autoimmune CSU. Further studies are required to assess whether the amount of histamine in basophils can be used to monitor or predict response to treatment in patients.

Positive basophil histamine release assay predicts insufficient response to standard-dosed omalizumab in patients with chronic spontaneous urticaria.

Positive basophil histamine release assay predicts insufficient response to standard-dosed omalizumab in patients with chronic spontaneous urticaria.

Omalizumab versus cyclosporin-A for the treatment of chronic spontaneous urticaria: can we define better-responding endotypes?

BackgroundChronic Spontaneous Urticaria (CSU) is characterized by recurrent wheals and/or angioedema for longer than 6-weeks. Guidelines recommend Omalizumab (Oma) as first-line and Cyclosporine-A (Cs-A) as second-line treatment in antihistamine resistant CSU. This step-wise algorithm might be time-consuming and costly. ObjectiveTo determine indicators of response to Oma or Cs-A in CSU patients. MethodsWe retrospectively analyzed data from seven centers in Turkey; the inclusion criteria for patients were to receive both Oma and Cs-A treatment (not concurrently) at some point in time during their follow-up. Clinical and laboratory features were compared between groups. ResultsAmong 110 CSU patients; 47 (42.7%) were Oma-responders, 15 (13.6%) were Cs-A-responders, and 24 (21.8%) were both Oma and Cs-A responders and 24 (21.8%) were non-responders to either drug. High CRP levels were more frequent in Cs-A-responders (72.7% vs. 40.3%; p = 0.055). Oma-responders had higher baseline UCT (Urticaria Control Test) scores (6 vs. 4.5; p = 0.045). Responders to both drugs had less angioedema and higher baseline UCT scores compared to other groups (33.3% vs. 62.8%; p = 0.01 and 8 vs. 5; p = 0.017). Non-responders to both drugs had an increased frequency in the female gender and lower baseline UCT scores compared to other groups (87.5% vs. 61.6%; p = 0.017 and 5 vs. 7; p = 0.06). Study LimitationsRetrospective nature, limited number of patients, no control group, the lack of the basophil activation (BAT) or BHRA (basophil histamine release assay) tests. ConclusionsBaseline disease activity assessment, which considers the presence of angioedema and disease activity scores, gender, and CRP levels might be helpful to predict treatment outcomes in CSU patients and to choose the right treatment for each patient. Categorizing patients into particular endotypes could provide treatment optimization and increase treatment success.

The Allergen-Specific IgE Concentration Is Important for Optimal Histamine Release From Passively Sensitized Basophils.

BackgroundThe basophil histamine release (HR) assay can be used for allergy diagnosis in addition to the conventional measurement of allergen-specific IgE (sIgE). Passive sensitization of basophils increases the versatility and allows testing the biological relevance of allergen-induced IgE cross-linking in any serum unbiased by the cellular component. However, not all the patient sera perform equally well and we hypothesized that the absolute level and fraction of sIgE affect the performance. Choosing birch pollen allergy as a model, we investigated the concentration of sIgE needed for successful passive sensitization using soluble- or matrix-fixed Bet v 1.MethodsTwenty-eight sera with Bet v 1 sIgE [7 sera within each allergy class (1: 0.1–0.70 kUA/L, 2: 0.71–3.50 kUA/L, 3: 3.51–17.50 kUA/L, and 4+: >17.50 kUA/L)] and a negative control serum pool were used to passively sensitize donor basophils, obtained from buffy coat blood (n = 3). The cells were incubated (30 min) with a soluble allergen (rBet v 1 from 0.2 to 50 ng/ml), matrix-fixed allergen (ImmunoCAP™ containing recombinant Bet v 1), or phorbol 12-myristate 13-acetate (PMA)/ionomycin mixture (maximal HR) and released histamine was quantified fluorometrically.ResultsThe lowest level of Bet v 1 sIgE generating a detectable HR (HR > 10% of maximal release) in all the 3 runs was found to be 1.25 kUA/L (corresponding to allergy class 2, 0.71–3.50 kUA/L). Furthermore, sera from allergy classes 3 and 4+ ascertained a significant reproducible HR: 42/42 vs. 5/21 in allergy class 1 and 15/21 in allergy class 2. Using ImmunoCAP™s containing Bet v 1 as a matrix-fixed allergen system, similar results were obtained where the lowest sIgE concentration mediating an HR was 1.68 kUA/L and 7/7 for both allergy classes 3 and 4+.ConclusionThe results demonstrate that the IgE titer is strikingly robust in predicting the ability to sensitize basophils and produce a measurable HR.

Detection of Circulating Peanut Components in Serum after Ingestion

Introduction: Detection of specific food allergens brought into circulation following ingestion is complicated by the minute amounts present in serum. We therefore aimed to assess the utility of selective removal of IgE against peanut components using ImmunoCAP combined with the basophil histamine release (HR) assay (BHRA) to identify the absorbed allergen components after ingestion of peanut. Methods: Serum from six healthy individuals was drawn before and 1 h after ingestion of 100 g peanut. Serum from two peanut allergic patients was depleted for IgE against single allergen components by incubation with ImmunoCAPs coupled with either Ara h 1; 2; 3 or 6 before donor basophils were passively sensitized with the serum preparations. The sensitized cells were challenged with serum obtained from the six individuals before and after ingestion of peanut, and HR was measured after serum provocation. Results: Ara h 2 and Ara h 6 were detected in serum 1 h after ingestion in 6/6 individuals by negative selection. Depletion of specific IgE against Ara h 2 or Ara h 6 almost completely abolished the response to serum provocation, indicating a sequence homology between the two allergen components in serum. Ara h 1 was demonstrated in 5/6 sera and Ara h 3 in 1/6 sera. Conclusion: This study is a proof of concept showing that passive sensitization of basophils with sera depleted of component-specific IgE can be used to identify food allergen components present in serum after ingestion.

Ligelizumab Achieves Freedom from Signs and Symptoms of Chronic Spontaneous Urticaria Regardless of the CU Index (Basophil Histamine Release Assay) Status at Baseline

A positive Chronic Urticaria Index (basophil histamine release assay [BHRA]) is indicative of type-2 autoimmune mechanism of chronic spontaneous urticaria (CSU). This analysis evaluates the response to ligelizumab, a next-generation anti-IgE-antibody, in CSU patients who were either BHRA negative or BHRA positive at baseline.

Autologous serum skin test reactions in chronic spontaneous urticaria differ from heterologous cell reactions.

Autoimmune chronic spontaneous urticaria (CSU) is due to mast cell (MC)-activating autoantibodies, which are screened for by the autologous serum skin test (ASST) and basophil tests (BTs). Many CSU patients are positive in only one of these tests. How often this occurs and why is currently unknown. To characterize the prevalence of mismatched ASST and BTs in CSU patients, and to investigate possible reasons for these mismatches. We determined the rates of ASST+/BT- and ASST-/BT+ mismatches in published CSU studies. We assessed sera from 48 CSU patients by ASST, two BTs (basophil histamine release assay, BHRA; basophil activation test, BAT), a MC histamine release assay (MCHRA) and by ex vivo skin microdialysis (SMD). The ASST/BT mismatch rate in published CSU studies was 31% (ASST+/BT-: 22%, ASST-/BT+: 9%). In our patients, the ASST/BHRA and ASST/BAT mismatch rate was 35.4% (ASST+/BHRA-: 18.8% and ASST-/BHRA+: 16.7%) and 31.3% (ASST+/BAT-: 6.3% and ASST-/BAT+: 25.0%), respectively, and the two BTs were significantly correlated (P=0.0002). The use of heterologous MCs, in vitro and in situ, instead of basophils produced similar results (MCHRA mismatch: 47.9%, ASST+/MCHRA-: 18.8%, ASST-/MCHRA+: 29.2%; SMD mismatch: 40.0%, ASST+/SMD-: 10.0% and ASST-/SMD+: 30.0%), and the MCHRA was highly correlated with SMD results (P=0.0002). The ASST and BTs show divergent results in a third of CSU patients. Mismatches cannot be explained by the choice of basophil assay, the type of heterologous cells exposed to CSU serum in vitro (basophils vs. mast cells), nor the experimental setting of heterologous skin mast cells (in vitro vs. in situ). Thus, serum-induced whealing, in CSU patients, seems to involve autologous skin signals modulating MC degranulation.

Predictors of treatment response in chronic spontaneous urticaria.

The current therapeutic algorithm for chronic spontaneous urticaria (CSU), endorsed by the international guideline, entails treatment escalation from second-generation H1 -antihistamines (sgAHs) to omalizumab and cyclosporine until complete response is achieved. Recently, several predictors of response to these treatment options have been described. Here, we discuss the most promising predictors of response and nonresponse to these treatments in CSU. A systematic search was performed by two independent researchers using the MEDLINE/PubMed database with specific keywords and 73 studies included in the review. Levels of evidence were categorized as strong (robust predictors), weak (emerging predictors) or no association, based on the outcome and number of studies available. High disease activity, high levels of C-reactive protein and D-dimer are robust predictors for a poor or no response to sgAHs. Poor or no response to omalizumab is robustly predicted by low serum levels of total IgE. A good response to cyclosporine is robustly predicted by a positive basophil histamine release assay, whereas low total IgE is an emerging predictor. The response to treatment with sgAHs, omalizumab and cyclosporine can be predicted by the use of markers that are readily available in routine clinical practice. Further studies are needed to confirm these predictors.

Autoimmune Diseases Are Linked to Type IIb Autoimmune Chronic Spontaneous Urticaria.

PurposePatients with chronic spontaneous urticaria (CSU) have an increased risk for comorbid autoimmune diseases. In this retrospective multicenter study of CSU patients, we evaluated clinical and laboratory features of CSU associated with a higher risk of comorbid autoimmune diseases.MethodsWe analyzed records of CSU patients (n = 1,199) for a history or presence of autoimmune diseases. Patients were diagnosed with type IIb autoimmune CSU (aiCSU) if all 3 tests were positive: autologous serum skin test (ASST), basophil histamine release assay (BHRA) and/or basophil activation test (BAT), and IgG autoantibodies against FcεRIα/IgE detected by immunoassay.ResultsTwenty-eight percent of CSU patients had at least 1 autoimmune disease. The most prevalent autoimmune diseases were Hashimoto's thyroiditis (HT) (≥ 21%) and vitiligo (2%). Two percent of CSU patients had ≥ 2 autoimmune diseases, most frequently HT plus vitiligo. Comorbid autoimmune diseases, in patients with CSU, were associated with female sex, a family history of autoimmune diseases, and higher rates of hypothyroidism and hyperthyroidism (P < 0.001). Presence of autoimmune diseases was linked to aiCSU (P = 0.02). The risks of having autoimmune diseases were 1.7, 2.9 and 3.3 times higher for CSU patients with a positive ASST, BHRA and BAT, respectively. In CSU patients, markers for autoimmune diseases, antinuclear antibodies and/or IgG anti-thyroid antibodies were associated with non-response to omalizumab treatment (P = 0.013).ConclusionsIn CSU, autoimmune diseases are common and linked to type IIb autoimmune CSU. Our results suggest that physicians assess and monitor all adult patients with CSU for signs and symptoms of common autoimmune diseases, especially HT and vitiligo.

Exploring the safety and effectiveness of subcutaneous autologous serum therapy versus conventional intramuscular autologous serum therapy in chronic urticaria: An observer-blind, randomized, controlled study.

Autologous serum therapy aims to supplement the existing pharmacotherapy in chronic urticaria by decreasing the antihistamine pill-burden and maintaining symptom-free interval. Subcutaneous autologous serum therapy further modifies the amount of serum (2 mL to 1 mL) and gauge of a needle (24G to 31G) to improve compliance and facilitate ease of application. To assess clinical effectiveness and safety of subcutaneous autologous serum therapy versus conventional intramuscular autologous serum therapy and to compare the quality of life in the two treatment arms. Institution-based, assessor-blind, prospective, randomized, parallel-group, active-controlled trial with 32 patients in each treatment arm and analyzed on a modified intention to treat principle. After baseline autologous serum skin test, autologous serum was injected as per randomization every week for 9 consecutive weeks. Among the study population, conventional intramuscular autologous serum therapy and subcutaneous autologous serum therapy had a comparable duration of disease (P = 0.164, Mann-Whitney U test), autoreactive status (P = 0.796), urticaria total severity score (P = 0.637) and urticaria activity score summed up over 7 days (P = 0.982). Both urticaria activity score summed up over 7 days and total severity score along with antihistamine pill-burden reduced significantly (P < 0.001, Friedman's analysis of variance) in both subcutaneous autologous serum therapy and conventional intramuscular autologous serum therapy from first follow-up onwards (P < 0.05, Post hoc Dunn's test). Significant improvement was noted in patient's as well as physician's global assessment of disease activity improvement scale (P < 0.001, Friedman's analysis of variance). Intergroup analysis showed that there was no significant difference in urticaria activity score summed up over 7 days either at baseline (P = 0.982, Mann-Whitney U test) or at study end (P = 0.398, Mann-Whitney U test). Similar comparable results were found in the total severity score at the end of the study (P = 0.345, Mann-Whitney U test). Dermatology life quality index showed marked improvement with both types of treatment (P < 0.0001, Wilcoxon test), and the intergroup comparison showed comparable dermatology life quality index values (P = 0.994, Mann-Whitney U test). The pain score at the injection site was more with conventional intramuscular autologous serum therapy than subcutaneous autologous serum therapy (P = 0.0115, Mann-Whitney test). Younger age and lower baseline total severity scores were associated with a better therapeutic response. Baseline urticaria activity score added up over a period of 7 days and total severity scores and the diameter of lesions showed a positive correlation with response pattern. Basophil histamine release assay not done. Logistics could not support follow-up beyond the end of treatment. Subcutaneous autologous serum therapy is not inferior to conventional intramuscular autologous serum therapy with the additional advantage of less pain and operational feasibility.

The quest for ingested peanut protein in human serum

There is mounting evidence that systemic uptake of food allergens is key to triggering anaphylaxis. However, direct proof for this theory is still lacking. The purpose of this study was to quantify the absorption and to determine the absorption kinetics of immunoreactive peanut protein in relation to the allergic response in human. Quantitative protein assays including mass spectrometry, dot blots and Western blotting were developed to determine the level of Ara h 2 absorption in human serum. The double monoclonal sandwich ELISA was applied to quantify absorbed Ara h 2 and 6, and the basophil histamine release assay and the human passive cutaneous anaphylaxis test were utilized to study the absorption kinetics of immunologically intact peanut proteins. The protein assays worked but were not sensitive enough to trace the minute amounts of absorbed Ara h 2 in human serum. The level of Ara h 6 in serum was found to be up to 0.2ng/mL, but Ara h 2 could not be detected with the ELISA. Both the in vivo and the in vitro methods were successful in demonstrating that: immunoreactive peanut protein was absorbed shortly after ingestion (≤5minutes); the peanut protein concentration peaks between 1 and 4hours; and peanut proteins can circulate for at least 48hours in the bloodstream. Ingested peanut protein is absorbed systemically and retains its immunoreactive capacity in human serum. However, the precise quantities and the implication for the elicitation of anaphylaxis remains to be elucidated.

Eosinopenia, in Chronic Spontaneous Urticaria, Is Associated with High Disease Activity, Autoimmunity, and Poor Response to Treatment

Chronic spontaneous urticaria (CSU) is characterized by the degranulation of skin mast cells and the influx of basophils and eosinophils to affected skin sites. Blood basopenia has been linked to severe antihistamine-resistant CSU and type IIb autoimmunity, whereas the role of eosinophils in CSU is largely unknown. To analyze data from 1613 patients with CSU from 2 centers to study the prevalence, role, and relevance of eosinopenia in CSU. Peripheral blood eosinophil and basophil counts were measured by automated hematology analyzers. Patient files were screened for clinical characteristics, results of laboratory tests, the autologous serum skin test, the serum-induced basophil histamine release assay, and response to second-generation H1-antihistamines and omalizumab. Ten percent of patients with CSU had eosinopenia. Eosinopenia was associated with the female sex, high disease activity, autologous serum skin test and basophil histamine release assay positivity, low total IgE, and high levels of C-reactive protein and IgG-antithyroperoxidase (P ≤ .007). Nonresponders to second-generation H1-antihistamines or omalizumab had significantly lower eosinophils as compared with responders (P < .05 and P < .01, respectively). Blood eosinophil counts correlated with basophil counts (r= 0.396; P < .001), and 81% of patients with CSU with undetectable eosinophils had basopenia. The combination of eosinopenia and basopenia is a better predictor of nonresponse to second-generation H1-antihistamines than eosinopenia alone (odds ratio of 9.5 vs 4.8). Eosinopenia in patients with CSU is associated with type IIb autoimmunity, high disease activity, and poor response to treatment. Eosinophils should be explored as biomarkers and investigated for their contribution to the pathogenesis of CSU.

Biomarkers and clinical characteristics of autoimmune chronic spontaneous urticaria: Results of the PURIST Study.

Autoimmune chronic spontaneous urticaria (aiCSU) is an important subtype of chronic spontaneous urticaria (CSU) in which functional IgG autoantibodies to IgE or its high-affinity receptor (FcεRI) induces mast cell degranulation and subsequent symptom development. However, it has not been tightly characterized. This study aimed to better define the clinical and immunological features and to explore potential biomarkers of aiCSU. This was a multinational, multicenter study of 182 CSU patients. The clinical features studied included: urticaria activity and impact (UAS7 and quality of life); autologous serum skin test (ASST); IgG anti-FcεRI and IgG anti-IgE; IgG-anti-thyroperoxidase (IgG anti-TPO); total serum IgE; and basophil reactivity (BASO) using the basophil activation test (BAT) and basophil histamine release assay (BHRA). Of the 182 patients, 107 (59%) were ASST+, 46 (25%) were BASO+, and 105 (58%) were IgG anti-FcεRI+/IgE+. Fifteen patients (8%) fulfilled all three criteria of aiCSU. aiCSU patients appeared more severe (UAS7 21 vs 9 P<0.016) but showed no other clinical or demographic differences from non-aiCSU patients. aiCSU patients also had markedly lower total IgE levels (P<0.0001) and higher IgG anti-TPO levels (P<0.001). Of biomarkers, positive BAT and BHRA tests were 69% and 88% predictive of aiCSU, respectively. aiCSU is a relatively small but immunologically distinct subtype of CSU that cannot be identified by routine clinical parameters. Inclusion of BHRA or BAT in the diagnostic workup of CSU patients may aid identification of aiCSU patients, who may have a different prognosis and benefit from specific management.

Immunological effects and potential mechanisms of action of autologous serum therapy in chronic spontaneous urticaria.

Autoimmune processes are considered to play a major role in the pathogenesis of chronic spontaneous urticaria (CSU). Very recently, interleukin 24 (IL-24) has been identified as an immunoglobulin E (IgE) autoantigen in CSU. Some studies revealed that notably autologous serum skin test (ASST)-positive CSU patients may benefit from autohemotherapy; however, the mechanisms of action remain unknown. We aimed to investigate the immunological effects of autologous serum injections in ASST-positive CSU patients. Sixty-six ASST-positive CSU patients were treated with weekly intramuscular autologous serum injections for 8 weeks and followed up for 12 weeks. Urticaria activity score (UAS7) and Dermatology Life Quality Index (DLQI) were assessed. The ASST was done at baseline, week 9 and week 21. Serum samples (baseline, weeks 9, 13 and/or 21) were analysed for the levels of IgE-anti-IL-24 and immunoglobulin G (IgG)-anti-IL-24 via ELISA and their ability to release histamine in basophils [basophil histamine release assay (BHRA)]. Autologous serum therapy resulted in a substantial improvement in disease activity and quality of life after 8 and 20 weeks. Twenty-eight percent and 34% of patients turned ASST-negative in weeks 9 and 21, respectively, but there was no link between their response to treatment and changes of ASST results. Also, no significant or relevant changes in BHRA were observed. In contrast, autologous serum therapy significantly decreased IgE-anti-IL-24 serum levels, but not IgG-anti-IL-24 serum levels, in responders but not in non-responders. Our findings suggest that the immunological effects of autologous serum therapy include a reduction in IgE-anti-IL24 autoantibodies, which may contribute to the pathogenesis of CSU.

Factors Predicting the Response to Cyclosporin Treatment in Patients With Chronic Spontaneous Urticaria: A Systematic Review.

PurposeThis study aimed to systemically review literature relating to factors that could potentially predict a favorable response to cyclosporine A (CsA) treatment for chronic spontaneous urticaria (CSU).MethodsA systematic literature review was done according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis recommendations.ResultsA total of 13 studies (404 patients with CSU and 200 healthy patients) were included. There were only 1 randomized controlled trial (RCT) and 12 non-RCTs. Our systematic review showed that positive autologous serum skin test results, positive baseline basophil histamine release assays, positive baseline basophil activation test responses, elevated baseline plasma D-dimer levels, elevated baseline serum interleukin (IL)-2, IL-5, and tumor necrosis factor-alpha (TNF-α) levels, and low baseline serum IgE levels might assist in predicting favorable CsA responses in CSU patients. Decreased plasma D-dimer levels; and decreased serum IL-2, IL-5, and TNF-α levels were reported to be correlated with clinical improvement after CsA treatment.ConclusionsSince most positive results were from non-RCT articles and some data were still inconsistent, this systematic review identified no reliable practical biomarker for predicting CsA treatment response in patients with CSU. There were no positive predictors with good consistency and mechanical plausibility.

Predicting Response to Omalizumab in Chronic Urticaria Based on Biomarkers

Chronic urticaria (CU) is characterised by intense recurrent itch, wheals, and/or angioedema, persisting for &gt;6 weeks. CU can be subdivided into chronic spontaneous urticaria and chronic inducible urticaria; the latter usually appears with physical stimuli, such as heat, cold, pressure, and sunlight. The recommended treatment for CU is non-sedating oral antihistamines, administered up to four times a day. The monoclonal antibody omalizumab (anti-IgE) is recommended as an add-on therapy for patients with antihistamine-refractory CU. The fluctuating nature of urticaria symptoms and varying response to omalizumab often makes it difficult to predict the response to omalizumab; this often leads to individualised dosage regimens for CU patients. However, being able to predict the response to omalizumab treatment would lead to an improvement in dosage regimens and treatment plans in the clinical setting. Several studies have investigated potential CU biomarkers; however, no reliable biomarkers have been discovered that can be used to assess the treatment response to omalizumab in the clinic. Some potential biomarkers, such as plasma D-dimer, serum total IgE levels, the basophil histamine release assay, the autologous serum skin test, and the basophil activation test, have been suggested for predicting disease activity and response to omalizumab but are not implemented routinely in clinical practice. This paper presents an overview of the various biomarkers associated with response to omalizumab in CU.

Diagnostic and Therapeutic Principles In Allergy

The incidence of allergic diseases, like asthma, allergic rhinitis, and food allergy, is increasing in Westernized countries. This chapter discusses the importance of taking a careful and focused history and physical examination, as well as the laboratory studies that can be used to demonstrate the presence of allergic sensitization. Treatment for allergic disease is discussed, with an emphasis on new biologic therapies that have been developed. Finally, the chapter explores relatively new studies on the potential for interventions to prevent food allergy. Allergy is defined as an untoward physiologic event mediated by immune mechanisms, usually involving the interaction between an allergen and the allergic antibody, immunoglobulin E (IgE). Allergic reactions typically occur due to exposure to either airborne allergens, foods, drugs, chemicals, or Hymenoptera (such as wasps, bees and fire ants). Allergies manifest in numerous ways, including allergic asthma, allergic rhinoconjunctivitis, urticaria, eczema, and in its most severe form, anaphylaxis. This review contains 4 videos, 5 figures, 4 tables and 42 references Key Words: Delayed allergic reaction (Alpha-gal), Allergy diagnosis, Measurement of specific IgE, Allergy and asthma therapies, Anticytokine therapy (dupilumab, mepolizumab, reslizumab), AntiIgE therapy (omalizumab), Allergy skin testing, Basophil histamine release assay

Biomarkers of treatment efficacy in patients with chronic spontaneous urticaria.

Background. Currently there are no biomarkers useful to predict the future evolution and the therapeutic response in patients with chronic spontaneous urticaria (CSU). Objective. To review the available information on biomarkers that might be applied for the follow up of the response to guideline recommended therapies for CSU. Methods. A review of the medical literature on CSU potential clinical and laboratory biomarkers in PubMed and MEDLINE including the terms urticaria, chronic urticaria, chronic idiopathic urticaria, chronic spontaneous urticaria, antihistamines (AHs), omalizumab (OMA), cyclosporine (CyA), and treatment. Results. Clinical manifestations that were associated to poor responses to AHs were atopy, asthma, rhinitis / rhinosinusitis, thyroid disease, hypertension, higher disease activity and duration. Laboratory markers of AH resistance that have been reported include Complement C5a fraction, Autologous Serum Skin Test (ASST), Basophil Activation Test (BAT), D-dimer and LCN2 adipokine. Basophil Histamine Release Assay (BHRA), ASST, and basophil CD203c-upregulating activity in the serum correlated with favorable response to OMA, whereas disease duration and severity, BAT, BHRA, and D-dimer levels were associated with better responses to CyA. Conclusion. Some promising biomarkers useful for patient management in CSU, have been identified in the literature. There is, however, an urgent need of new, easy-to-perform markers that can be made widely available for the optimal care of patients suffering CSU.

Advances in Chronic Urticaria

In recent years, there have been important advances in our knowledge and management of chronic urticaria, a frequently debilitating disease. This review will be an update on the significant progress made in diagnostic and therapeutic procedures, as well as the classification, pathophysiology and assessment tools available for urticaria. Some of the latest advances will be detailed, including new findings that shed light on the mechanism of chronic urticaria. Updated information on optimal management of chronic urticaria will be discussed, including evidence on newer therapy, primarily the humanized monoclonal anti-IgE antibody, omalizumab. This is now considered to be third-line therapy after licensed doses of antihistamines and unlicensed updosing of antihistamines fourfold. Further understanding of the pathogenesis of chronic urticaria may help explain the mechanisms involved in the action of treatments. This would then aid the clinician with the appropriate diagnostic tests and therapeutic options. Extensive research on the administration of omalizumab has determined optimal dosage, the interval and duration of treatment. Recent studies have significantly advanced the treatment of chronic urticaria refractory to antihistamines, and the stepwise treatment algorithm has been updated in accordance with new evidence. Biomarkers, such as the basophil histamine release assay and autologous skin serum test, have been useful to identify chronic autoimmune urticaria, a subset of chronic urticaria, and may aid selection of third-line therapy, as well as predict speed of response and prognosis.