Changes in basophil activation during immunotherapy with house dust mite and mugwort in patients with allergic rhinitis

BACKGROUND: The basophil activation test (BAT) is a promising tool for monitoring allergen-specific immunotherapy responses. OBJECTIVE: We aimed to investigate the changes in basophil activation in response to the inhalant allergens of house dust mite (HDM) and mugwort pollen during immunotherapy in patients with allergic rhinitis. METHODS: We enrolled patients with allergic rhinitis who were to receive subcutaneous immunotherapy for the inhalant allergens HDM or mugwort. A BAT was performed to assess CD63 upregulation in response to allergen stimulation using peripheral blood collected from the patients prior to immunotherapy and at 3, 6, 12, and 24 months after beginning immunotherapy. Rhinitis symptoms were evaluated using the rhinitis quality of life questionnaire (RQLQ) at 1-year intervals. RESULTS: Seventeen patients (10 with HDM sensitivity, 3 with mugwort sensitivity, and 4 with sensitivity to both HDM and mugwort) were enrolled in the study. Basophil reactivity to HDM did not change significantly during 24 months of immunotherapy. However, a significant reduction in basophil reactivity to mugwort was observed at 24-month follow-up. There was no significant association between the change in clinical symptoms by RQLQ and the change in basophil reactivity to either allergen. The change in allergen-specific basophil reactivity to HDM was well correlated with the change in nonspecific basophil activation induced by anti-FcεRI antibody, although basophil reactivity to anti-FcεRI antibody was not significantly reduced during immunotherapy. CONCLUSION: Suppression of CD63 upregulation in the BAT was only observed with mugwort at 2-year follow-up. However, the basophil response did not reflect the clinical response to immunotherapy.

Diagnostic value of basophil activation test in food allergy in children / 中华实用儿科临床杂志

At present,diagnostic programs of food allergy in children mainly include medical history,skin prick test,detection of serum specific immunoglobulin E (sIgE) antibody,food challenge test,and so on.Among them,skin prick test and detection of sIgE antibody are used as primary screening tests with high diagnostic sensitivity while low specificity.Additionally,double-blind placebo-controlled food challenge test is the gold standard for the diagnosis,but it is faced with a potential risk of causing systemic allergic reactions,resulting in its rare application in clinic.Moreover,basophil activation test,as an in vitro test for allergen diagnosis,has significant value in diagnosis of food allergy in children due to its high specificity and safety.Besides,basophil activation test can also be used to evaluate the severity of food allergy in children,monitor immune therapy,detect trace allergens,and so on.

Usefulness of In Vivo and In Vitro Diagnostic Tests in the Diagnosis of Hypersensitivity Reactions to Quinolones and in the Evaluation of Cross-Reactivity: A Comprehensive Study Including the Latest Quinolone Gemifloxacin

PURPOSE: Reports evaluating diagnosis and cross reactivity of quinolone hypersensitivity have revealed contradictory results. Furthermore, there are no reports investigating the cross-reactivity between gemifloxacin (GFX) and the others. We aimed to detect the usefulness of diagnostic tests of hypersensitivity reactions to quinolones and to evaluate the cross reactivity between different quinolones including the latest quinolone GFX. METHODS: We studied 54 patients (mean age 42.31±10.39 years; 47 female) with 57 hypersensitivity reactions due to different quinolones and 10 nonatopic quinolone tolerable control subjects. A detailed clinical history, skin test (ST), and single-blind placebo-controlled drug provocation test (SBPCDPT), as well as basophil activation test (BAT) and lymphocyte transformation test (LTT) were performed with the culprit and alternative quinolones including ciprofloxacin (CFX), moxifloxacin (MFX), levofloxacin (LFX), ofloxacin (OFX), and GFX. RESULTS: The majority (75.9%) of the patients reported immediate type reactions to various quinolones. The most common culprit drug was CFX (52.6%) and the most common reaction type was urticaria (26.3%). A quarter of the patients (24.1%) reacted to SBPCDPTs, although their STs were negative; while false ST positivity was 3.5% and ST/SBPCDPTs concordance was only 1.8%. Both BAT and LTT were not found useful in quinolone hypersensitivity. Cross-reactivity was primarily observed between LFX and OFX (50.0%), whereas it was the least between MFX and the others, and in GFX hypersensitive patients the degree of cross-reactivity to the other quinolones was 16.7%. CONCLUSIONS: These results suggest that STs, BAT, and LTT are not supportive in the diagnosis of a hypersensitivity reaction to quinolone as well as in the prediction of cross-reactivity. Drug provocation tests (DPTs) are necessary to identify both culprit and alternative quinolones.

<b>Basophil Activation Test for Kampo Medicines :Proper Concentration to Avoid False Positive Result</b> / 日本東洋医学雑誌

Recently, basophil activation test (BAT) has been applied to the diagnosis of drug allergy. We performed BAT for various Kampo medicines taken by 12 cooperators to evaluate the concentration which arouse nonspecific reaction during incubation in BAT. When whole blood of each was incubated for 24 hours with each Kampo medicine, false positive results were frequently observed. After 1-hour incubation with Kampo medicine at high concentration (1/312.5), false positive results were sometimes observed. These results suggest that in the diagnosis of Kampo-medicine adverse reactions, BAT should be performed in the condition of 1-hour incubation with lower concentration (1/1250 or lower).

Diagnostic Significance of BAT in Anaphylaxis to Non-ionic Contrast Media / 法医学杂志

Objective To investigate the diagnostic significance of basophil activation test (B A T) in ana-phylaxis to non-ionic contrast media through testing the content of CD 63, m ast cell-carboxypeptidase A 3 (M C-CPA 3), and term inal com plem ent com plex SC5b-9 of the individuals by testing their levels in the norm al im m une group and the anaphylaxis groups to β-lactam drugs and non-ionic contrast media. Methods The CD 63 expression of basophilic granulocyte in blood w as detected by flow cytom etry. The levels of M C-CPA 3 in blood serum and SC5b-9 in blood plasm a w ere detected by ELISA . Results The CD 63 expression of basophilic granulocyte in blood, the levels of M C-CPA 3 and SC5b-9 of anaphylaxis to non-ionic contrast media and β-lactam drugs w ere significantly higher than that in norm al im m une group (P<0.05). Conclusion There is activation of basophilic granulocytes, m ast cells and com plem ent system in anaphylaxis to non-ionic contrast media. B A Tcan be used to diagnose the anaphylaxis to non-ionic contrast media.

Serum Specific IgE to Thyroid Peroxidase Activates Basophils in Aspirin Intolerant Urticaria

Thyroid antibodies are frequently observed in urticaria patients, but their roles in urticaria are not clearly elucidated. We investigated the role of serum specific IgE to thyroid peroxidase (TPO) in patients with aspirin intolerant acute urticaria (AIAU) and aspirin intolerant chronic urticaria (AICU). We recruited 59 AIAU and 96 AICU patients with 69 normal controls (NC). Serum specific IgE to TPO was measured by manual direct ELISA, and CD203c expressions on basophil with additions of TPO were measured to prove a direct role of TPO in effector cells. The prevalences of serum specific IgE to TPO were significantly higher in AIAU (15.2%) and AICU groups (7.5%) compared to NC (0%, P=0.018: P=0.013, respectively). Flow cytometry showed CD203c induction in a dose dependent manner with serial additions of TPO in some AIAU and AICU patients having high specific IgE to TPO. Our findings show that the prevalence of serum specific IgE to TPO was significantly higher in both AIAU and AICU patients than in NC. It is suggested that specific IgE to TPO play a pathogenic role in AIAU and AICU.

Basophil Activation Test with Food Additives in Chronic Urticaria Patients

The role of food additives in chronic urticaria (CU) is still under investigation. In this study, we aimed to explore the association between food additives and CU by using the basophil activation test (BAT). The BAT using 15 common food additives was performed for 15 patients with CU who had a history of recurrent urticarial aggravation following intake of various foods without a definite food-specific IgE. Of the 15 patients studied, two (13.3%) showed positive BAT results for one of the tested food additives. One patient responded to monosodium glutamate, showing 18.7% of CD203c-positive basophils. Another patient showed a positive BAT result to sodium benzoate. Both patients had clinical correlations with the agents, which were partly determined by elimination diets. The present study suggested that at least a small proportion of patients with CU had symptoms associated with food additives. The results may suggest the potential utility of the BAT to identity the role of food additives in CU.

Recent applications of basophil activation tests in the diagnosis of drug hypersensitivity

Immediate-type drug hypersensitivity is an increasingly significant clinical issue; however, the diagnosis is frequently hindered due to lack of safe and precise diagnostic tests. Flow cytometry-assisted basophil activation test is a safe in vitro diagnostic tool for assessing basophil activation upon allergen stimulation. In this review, we have summarized current literature on the diagnostic utilities, new indications, and methodological aspects of the basophil activation test for the diagnosis of drug hypersensitivity.

CD63 e CD123 expressão, autoanticorpos IgG e acurácia do teste do soro autólogo em pacientes com urticária crônica / CD63 and CD123 expression, IgG autoantibody and accuracy of autologous serum test in patients with chronic urticaria

INTRODUÇÃO: Na urticária crônica (UC), o teste cutâneo do soro autólogo (TCSA) pode sugerir a etiologia autoimune. Recentemente, uma nova técnica laboratorial denominada teste de ativação de basófilos (TAB) vem sendo utilizada para esse diagnóstico. OBJETIVOS: Analisar o TCSA em relação ao TAB, assim como avaliar os receptores da interleucina 3 (IL3) (CD123) e a presença de autoanticorpos da classe de imunoglobulina G (IgG) inespecíficos ligados aos basófilos de pacientes com UC. MÉTODOS: Estudamos 33 adultos com UC espontânea com idade média de 42,5 + 14 anos. Por meio da citometria de fluxo foi feita a análise da expressão das moléculas CD63 em basófilos de um doador atópico após o estímulo pelo soro dos pacientes com UC. Também realizamos a pesquisa da expressão da molécula CD123 e de autoanticorpos IgG inespecíficos. RESULTADOS: O odds ratio (OR) entre o TCSA e o TAB foi de 1 (intervalo de confiança [IC] 95 por cento: 0,22-4,5). O TCSA para o diagnóstico da UC autoimune mostrou acurácia de 54,5 por cento, sensibilidade de 66 por cento, especificidade de 33 por cento, valor preditivo positivo de 63 por cento e valor preditivo negativo de 36 por cento. Não houve diferença estatística entre os grupos estudados quanto à média de expressão dos anticorpos IgG inespecíficos e das moléculas CD123 (para um p < 0,05). DISCUSSÃO: Este estudo demonstrou baixa precisão do TCSA no diagnóstico da UC autoimune; o grupo de pacientes com TCSA positivo não mostrou diferença estatística em relação ao grupo com TCSA negativo nos demais aspectos analisados. CONCLUSÃO: Pelos poucos estudos existentes e pela relevância do assunto, acreditamos na necessidade de mais estudos abordando esses aspectos.

INTRODUCTION: The autologous serum skin test (ASST) may suggest an autoimmune etiology in chronic urticaria (CU). A new laboratory technique called basophil activation test (BAT) has been currently employed for its diagnosis. OBJECTIVE: To analyze ASST in relation to BAT as well as to evaluate interleukin 3 (IL3) receptors (CD123) and non-specific immunoglobulin G (IgG) autoantibodies bound to basophils in patients with chronic urticaria. METHODS: We studied 33 adults with CU and mean age of 42.5 + 14 years. After stimulation by serum from patients with CU, CD63 expression on basophils from one atopic donor was analyzed by flow cytometry. Furthermore, we investigated CD123 and IgG autoantibody expressions. RESULTS: The odds ratio (OR) between ASST and BAT was 1.00 (95 percent confidence interval [CI]: 0.22 to 4.5). The ASST for autoimmune CU diagnosis showed an accuracy of 54.5 percent, sensitivity of 66 percent, specificity of 33 percent, positive predictive value of 63 percent, and negative predictive value of 36 percent. There was no statistical difference between the studied groups as to mean non-specific IgG and CD123 expressions (for a p < 0.05). DISCUSSION: This study demonstrated that ASST has low accuracy in the diagnosis of autoimmune CU. Concerning other analyzed aspects, there was no statistical difference between positive ASST and negative ASST. CONCLUSIONS: Due to insufficient studies in this area and the relevance of this issue, further investigation is required.

Beef-Induced Anaphylaxis Confirmed by the Basophil Activation Test

Beef allergies are relatively rare, especially in adults. However, clinical manifestations can vary from urticaria, angioedema, anaphylaxis to gastrointestinal symptoms. Currently available tests, such as skin testing or in vitro determination of beef-specific immunoglobulin E (IgE), do not provide an accurate diagnosis of beef allergy. The recent development of the basophil activation test (BAT) presents a new opportunity for the diagnosis of food allergies. Here, we report a 37-year-old woman with a history of recurrent generalised urticaria, nausea, vomiting and hypotension after ingestion of beef, suggesting a beef allergy. Although the skin prick test and serum specific IgE to beef, pork and milk allergens showed negative results using commercial kits, the BAT showed significant upregulation of CD203c in a dose-dependent manner compared to both non-atopic and atopic controls. To our knowledge, this is the first case study of beef allergy consisting of a non-IgE-mediated reaction. The detection of food allergies using direct basophil activation is suggested to complement conventional diagnostic tests.