Basophil activation test (BAT) or the mast cell activation test (MAT) are two in vitro tests that are currently being studied in food allergy as diagnostic tools as an alternative to oral food challenges (OFCs). We conducted a meta-analysis on BAT and MAT, assessing their specificity and sensitivity in diagnosing peanut allergy. Six databases were searched for studies on patients suspected of having peanut allergy. Studies using BAT or MAT to peanut extract and/or component as diagnostic tools with results given in percentage of CD63 activation were included in this meta-analysis. Study quality was evaluated with the QUADAS-2 tool. On the 11 studies identified, eight focused exclusively on children, while three included a mixed population of adults and children. Only one study provided data on MAT, precluding us from conducting a statistical analysis. The diagnostic accuracy of BAT was higher when stimulated with peanut extract rather than Ara h 2 with a pooled specificity of 96% (95% CI: 0.89-0.98) and sensitivity of 0.86 (95% CI: 0.74-0.93). The sensitivity and specificity of BATs in discriminating between allergic and sensitized patients were studied as well, with pooled analysis revealing a sensitivity of 0.86 (95% CI: 0.74; 0.93) and a specificity of 0.97 (95% CI: 0.94, 0.98). BATs, when stimulated with peanut extracts, exhibit a satisfactory sensitivity and specificity for the diagnosis of peanut allergy and can help to discriminate between allergic individuals and those only sensitized to peanuts. More investigations on the potential for MATs diagnostic methods are warranted.

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Chronic spontaneous urticaria (CSU) is believed to be Autoimmune (aiCSU) (type IIb CSU) in at least 8% of patients, associated with mast cell-activating IgG autoantibodies. Basophil tests such as the basophil activation test (BAT) and basophil histamine release assay (BHRA) are considered the best single tests for an aiCSU diagnosis. To date, the strength of associations among a positive BAT and/or BHRA (BAT/BHRA+) and CSU features, patient demographics, and response to treatment remains poorly characterized.
To evaluate the strength of current evidence on basophil tests as parameters for CSU characteristics.
We performed a systematic literature search and review to assess the relationship between BAT/BHRA+ and clinical and laboratory parameters of CSU. Of 1,058 records found in the search, 94 studies were reviewed by experts in urticaria and 42 were included in the analysis.
In CSU patients, BAT/BHRA+ showed a strong level of evidence for an association with high disease activity and low levels of total IgE. A weak level of evidence was shown for the association of BAT/BHRA+ and the presence of angioedema, and basopenia.
Our results suggest that aiCSU defined by BAT/BHRA+ is more active or severe and is linked to other aiCSU markers such as low total IgE/basopenia. Basophil tests should be standardized and implemented in routine clinical care to improve the diagnosis and treatment of patients with aiCSU.

Hymenoptera venom immunotherapy (HVI) is a long-term effective treatment to avoid new systemic reactions in patients with Hymenoptera allergy. The sting challenge test is considered the gold standard to confirm the tolerance. However, the use of this technique is not generalized in clinical practice, being the basophil activation test (BAT), which functionally explores allergen response, an alternative that does not entail any of the provocation risks associated with the sting challenge test. This study reviews the publications that used the BAT to follow up and evaluate the success of the HVI. Studies assessing the changes between a baseline BAT before the start and BATs performed between the starting and maintenance phases of the HVI were selected. Ten articles were found, comprising information from 167 patients, of which 29% used the sting challenge test. The studies concluded the importance of evaluating the responses with submaximal allergen concentrations, which reflect basophil sensitivity, to monitor the HVI using the BAT. It was also observed that changes in the maximum response (reactivity) could not reflect the clinical status of tolerance, particularly in the initial phases of HVI.
La inmunoterapia con veneno de himenópteros (IVH) es, a largo plazo, un tratamiento eficaz para evitar nuevas reacciones sistémicas en pacientes con alergia a este tipo de insectos. La prueba de repicadura controlada es el estudio de referencia para confirmar la tolerancia del individuo. Sin embargo, no se ha generalizado su indicación clínica, por lo que la prueba de activación de basófilos (TAB) resulta una buena alternativa, pues valora de manera funcional la respuesta al alérgeno y está exenta de los riesgos asociados con la provocación. En esta revisión se explora la utilidad de la TAB en el seguimiento y valoración del éxito de la IVH. Se seleccionaron estudios que evalúan los cambios entre una TAB basal y en otro momento de la fase de inicio o mantenimiento de la IVH. Se incluyeron 10 estudios con datos de 167 pacientes, de los que el 29% había tenido prueba de repicadura controlada. Para vigilar la eficacia de la IVH debe explorarse la respuesta del basófilo, con la determinación de las concentraciones submáximas del alérgeno, que reflejan la sensibilidad del basófilo. Los cambios en la respuesta máxima (reactividad) no pueden aportar información del estado de tolerancia, especialmente en las fases iniciales de la IVH.

Type I allergies are pathological, type 2 inflammatory immune responses against otherwise harmless environmental allergens that arise from complex interactions between different types of immune cells. Activated immune cells undergo extensive changes in phenotype and function to fulfill their effector functions. Hereby, activation, differentiation, proliferation, migration, and mounting of effector responses require metabolic reprogramming. While the metabolic changes associated with activation of dendritic cells, macrophages, and T cells are extensively studied, data about the metabolic phenotypes of the other cell types critically involved in allergic responses (epithelial cells, eosinophils, basophils, mast cells, and ILC2s) are rather limited. This review briefly covers the basics of cellular energy metabolism and its connection to immune cell function. In addition, it summarizes the current state of knowledge in terms of dendritic cell and macrophage metabolism and subsequently focuses on the metabolic changes associated with activation of epithelial cells, eosinophils, basophils, mast cells, as well as ILC2s in allergy. Interestingly, the innate key cell types in allergic inflammation were reported to change their metabolic phenotype during activation, shifting to either glycolysis (epithelial cells, M1 macrophages, DCs, eosinophils, basophils, acutely activated mast cells), oxidative phosphorylation (M2 macrophages, longer term activated mast cells), or fatty acid oxidation (ILC2s). Therefore, immune metabolism is of relevance in allergic diseases and its connection to immune cell effector function needs to be considered to better understand induction and maintenance of allergic responses. Further progress in this field will likely improve both our understanding of disease pathology and enable new treatment targets/strategies.

BACKGROUND: Thiocolchicoside is a muscle relaxant, anti-inflammatory, and analgesic. Administered orally, intramuscularly, or topically, this drug is used in the symptomatic treatment of muscular spasms and rheumatologic disorders. Despite its extensive use, thiocolchicoside is a very rare sensitizer.
OBJECTIVE: To evaluate IgE-mediated reaction to thiocolchicoside by basophil activation test.
METHODS: Allergological work-up with skin prick tests, intradermal tests and basophil activation test with thiocolchicoside.
RESULTS: We report the first case of immediate reaction to thiocolchicoside confirmed by basophil activation test in addition to positive skin tests.
CONCLUSIONS: BAT can be considered a complementary diagnostic tool to demonstrate an IgE-mediated reaction also for muscle relaxant drugs.

The major challenge of allergy diagnosis lies in the development of accessible and reliable diagnostics allowing correct prediction of the clinical outcome following exposure to the offending allergen(s) and cross-reactive structures. Since the late nineties, evidence has accumulated that flow-assisted analysis and quantification of ex vivo-activated basophils (according to the basophil activation test [BAT]) might meet this requirement for different IgE-dependent allergies and particular forms of autoimmune urticaria. Other so-called nondiagnostic applications of the BAT involve therapeutic monitoring, follow-up of natural histories, and identification of allergenic recognition sites. However, it has also become clear that appropriate use of the BAT necessitates knowledge about degranulation metrics and guidance to guarantee correct execution and interpretation of the results. Here, we have reviewed the most relevant applications and limitations of the BAT. Some personal statements and views about its perspectives are made.

Perioperative hypersensitivity reactions (POH) constitute a clinical and diagnostic challenge, a consequence of heterogeneous clinical presentations, and multiple underlying pathomechanisms. POH do not necessarily involve an allergen-specific immune response with cross-linking of specific immunoglobulin E (sIgE) antibodies on mast cells and basophils. POH can also result from alternative specific and non-specific effector cell activation/degranulation such as complement-derived anaphylatoxins and off-target occupancy of mast cell, basophil, or both surface receptors. Moreover, POH and anaphylaxis can occur independent from mast cell and basophil degranulation. The manifestations of POH primarily affect the cardiovascular, respiratory, and integumentary systems. POH present within the context of surgical or procedural pathology and the effects of surgical and anaesthetic techniques on pre-existing physiological reserve. The majority of cases of appropriately-treated intraoperative anaphylaxis can be considered a compensated cardiovascular anaphylaxis. With increasing severity of anaphylaxis, maldistribution and hypovolaemia lead to reduced venous return and circulatory failure. Treatment with a combination of epinephrine and i.v. fluid is critical for successful resuscitation, although the excessive use of epinephrine without adequate volume expansion may be deleterious. Neural control of the airways is important in the pathophysiology of bronchospasm. Anticholinergic drug premedication is beneficial in patients with hyperreactive airways. Pulmonary oedema can result from a combination of pulmonary capillary hypertension, incompetence of the alveolocapillary membrane, or both. Angioedema can be distinguished mechanistically into histaminergic and non-histaminergic (e.g. bradykinin-mediated). An understanding of the molecular mechanisms and pathophysiology of POH are essential for the immediate management and subsequent investigation of these cases.

BACKGROUND: Stillbirth is defined by the WHO as birth of a fetus with no vital signs, at or over 28 weeks of pregnancy age. The estimation of time of death in stillbirth appears crucial in forensic pathology. However, there are no validated methods for this purpose.
OBJECTIVE: To perform a systematic review of the available literature regarding the estimation of the time of death in stillborn fetuses, in terms of hours or days.
METHODS: Electronic databases were searched from their inception to August 2018 for relevant articles. Macroscopic, histologic, and radiologic parameters were evaluated.
RESULTS: Nine studies with 664 stillborns were included. The evaluation of extent and location of fetal maceration signs showed good accuracy in estimating the time of death; by contrast, a dichotomous assessment of maceration (present vs absent) was found to be unreliable in a subsequent study. Histologic assessment of the loss of nuclear basophilia in fetal and placental tissues showed excellent accuracy; an \"autolysis equation\" was proposed to achieve an even higher accuracy in fetuses who had been dead for < 24 h. Magnetic resonance imaging of the lung parenchyma, pleural fluids, and brain parenchyma could estimate the death-to-autopsy time, but the results appeared weak and conflicting.
CONCLUSIONS: Pathologic examination, based on the assessment of maceration, and even more of the loss of nuclear basophilia, may be a reliable method to estimate the time of death in stillborn fetuses. Further studies should be encouraged to validate these results. Imaging techniques have not yet found application in this field.

Quantification of specific IgE (sIgE) antibodies constitutes an important measure to document anesthesia-related immediate hypersensitivity reactions (IHRs). However, only a few drug-specific assays are available and their predictive value is not known. In cases of non-IgE mediated IHRs, diagnosis might benefit from cellular tests such as basophil mediator release tests and basophil activation tests (BATs). To review the potential and limitations of quantification of sIgE, mediator release, and BAT in anesthesia-related IHRs, a literature search was conducted using the key words allergy, basophil activation, CD63, CD203c, diagnosis, drugs, hypersensitivity, flow cytometry, MRGPRX2, specific IgE antibodies, leukotrienes, histamine, and tryptase; this was complemented by the authors\' experience. The drugs and compounds that have predominantly been studied are neuromuscular blocking agents (NMBAs), β-lactams, latex, and chlorhexidine. For sIgE NMBA, sensitivity and specificity varies between 38.5% to 92% and 92% to 100%, respectively. For sIgE β-lactams, sensitivity varies between 0% to 85% and specificity between 52% to 100%. sIgE to morphine should not be used in isolation to diagnose IHRs to NMBAs or opiates. sIgE for latex, and, in difficult cases, molecular diagnosis with quantification of sIgE to Hevea components constitute reliable diagnostics. For drugs, the sensitivity of BAT varies between 50% and 60% and specificity reaches 80% to 90%. Basophil mediator release tests seem to be abandoned and supplanted by BATs.