Basophil Histamine Release by RNA, DNA and Aggregated IgG Examined in Rheumatoid Arthritis and Systemic Lupus Erythematosus

Basophils from patients with rheumatoid arthritis (RA) respond to RNA, DNA and immune complexes [aggregated IgG] with histamine release. The RNA response was well correlated to the clinical activity of the disease since histamine liberation was found in all patients with severe activity, whereas no liberation was observed in patients with moderate or quiescent activity. A less significant correlation was obtained with DNA and aggregated IgG. In contrast, no response was obtained with RNA, DNA and aggregated IgG in patients with systemic lupus erythematosus (SLE) or in controls. In the RA and the SLE groups no significant correlation was found between the response of RNA, DNA and aggregated IgG and the serum titres of anti-DNA and antinuclear antibodies. No difference in basophil cell count in peripheral blood and basophil histamine content was found between RA. SLE and controls. Our results point 10 an involvement of an autoimmune type I reaction in the pathogenesis of RA directed against the nuclear components RNA and DNA and against immune complexes.     

EAACI/GA2LEN task force consensus report: the autologous serum skin test in urticaria

Injection of autologous serum collected during disease activity from some patients with chronic spontaneous urticaria (CU) into clinically normal skin elicits an immediate weal and flare response. This observation provides a convincing demonstration of a circulating factor or factors that may be relevant to the understanding of the pathogenesis and management of the disease. This test has become known as the autologous serum skin test (ASST) and is now widely practised despite incomplete agreement about its value and meaning, the methodology and the definition of a positive response. It should be regarded as a test for autoreactivity rather than a specific test for autoimmune urticaria. It has only moderate specificity as a marker for functional autoantibodies against IgE or the high affinity IgE receptor (FcεRI), detected by the basophil histamine release assay, but high negative predictive value for CU patients without them. It is usually negative in other patterns of CU, including those that are physically induced. Positive ASSTs have been reported in some subjects without CU, including those with multiple drug intolerance, patients with respiratory allergy and healthy controls, although the clinical implications of this are uncertain. It is essential that failsafe precautions are taken to ensure that the patient's own serum is used for skin testing and aseptic procedures are followed for sample preparation and handling. CU patients with a positive ASST (ASST⁺) are more likely to be associated with HLADR4, to have autoimmune thyroid disease, a more prolonged disease course and may be less responsive to H1-antihistamine treatment than those with a negative ASST (ASST⁻) although more evidence is needed to confirm these observations conclusively.     

体外嗜碱性粒细胞激活试验法的建立

目的 建立基于流式细胞仪检测的体外嗜碱性粒细胞激活试验（human basophil activation test,h-BAT）方法,并探索该方法用于Ⅰ型变态反应检查的可行性。方法 利用人源白血病嗜碱性粒细胞KU812在Ⅰ型变态反应过程中经阳性剂激活后,细胞特异性表面抗原CD63和CD203表达特异性增强的原理建立体外Ⅰ型变态反应模型,并同步用人组胺酶联免疫法进行验证。结果 确定以终浓度为2μg·mL^-1的N-甲酰甲硫氨酰-亮氨酰-苯丙氨酸为阳性剂,孵育2 h作为流式方法检测嗜碱性粒细胞激活的阳性成立条件,细胞相对组胺释放百分比增高结果进一步确认了阳性成立条件。结论 h-BAT法有测试简便、评价客观等优点,是一种较好的过敏反应细胞模型,可以用于现有豚鼠试验的替代。     

Perioperative anaphylaxis and investigations: a local study in Hong Kong

INTRODUCTIONData on local intraoperative anaphylaxis in Hong Kong is scarce, with few reviews available. We aimed to study the characteristics, presentations and workup results of cases referred to a local allergy clinic.METHODSA retrospective review was performed of patient referrals and workup results for suspected intraoperative anaphylaxis at Queen Mary Hospital drug allergy clinic in 2012–2016.RESULTSTryptase was checked in only 81.7% (49/60) of the cases, most of which showed elevation (71.4%, 35/49). Among the 59 patients who received a workup, 47 (79.7%) showed positive findings, with a particularly high yield in the tryptase-positive subgroup (88.6%, 31/35). Among the 54 patients who consented to skin tests (the most sensitive investigation), 43 (79.6%) cases were positive. Overall, neuromuscular blockers were the commonest cause (25.0%, 15/60) of intraoperative anaphylaxis, while antibiotics ranked second (23.3%, 14/60). The timing of reactions was an important indication of potential allergens. For example, the majority of the neuromuscular blocker allergies occurred during the induction phase, while all gelofusine allergic events were in the maintenance phase of anaesthesia. 13 (21.7%) out of 60 cases received subsequent general anaesthesia procedures, with no recurrence of allergic reactions.CONCLUSIONProper workup after an intraoperative anaphylactic event has a fairly good chance of identifying the causative allergen. These results are useful for patient management and the planning of subsequent anaesthetic procedures.     

Biomarkers of diagnosis and resolution of food allergy

Food allergy is increasing in prevalence, affecting up to 10% of children in developed countries. Food allergy can significantly affect the quality of life and well-being of patients and their families; therefore, an accurate diagnosis is of extreme importance. Some food allergies can spontaneously resolve in 50%-60% of cow’s milk and egg-allergic, 20% of peanut-allergic and 9% of tree nut-allergic children by school age. For that reason, food-allergic status should be monitored over time to determine when to reintroduce the food back into the child’s diet. The gold-standard to confirm the diagnosis and the resolution of food allergy is an oral food challenge; however, this involves the risk of causing an acute-allergic reaction and requires clinical experience and resources to treat allergic reactions of any degree of severity. In the clinical setting, biomarkers have been used and validated to enable an accurate diagnosis when combined with the clinical history, deferring the oral food challenge, whenever possible. In this review, we cover the tools available to support the diagnosis of food allergies and to predict food allergy resolution over time. We review the latest evidence on different testing modalities and how effective they are in guiding clinical decision making in practice. We also evaluate predictive test cut-offs for the more common food allergens to try and provide guidance on when challenges might be most successful in determining oral tolerance in children.     

Basophils exhibit antibacterial activity through extracellular trap formation

Basophils are primarily associated with immunomodulatory functions in allergic diseases and parasitic infections. Recently, it has been demonstrated that both activated human and mouse basophils can form extracellular DNA traps (BETs) containing mitochondrial DNA and granule proteins. In this report, we provide evidence that, in spite of an apparent lack of phagocytic activity, basophils can kill bacteria through BET formation.     

Not all chronic urticaria is "idiopathic"

Abstract: The aetiology of chronic urticaria in the majority of patients is elusive. The cause of physical urticarias (dermographism, delayed pressure urticaria, cold urticaria) is unkonown. We have identified a subset of chronic "idiopathic" urticaria patients, representing approximately 30% of the total in which the disease is caused by the presence of IgG autoantibodies against the high affinity IgE receptor (FcœRIα). This functional autoantibody stimulates normal (albeit vicarious) activation of mast cells and basophils via FcœRI, causing whealing and angioedema. Anti-FcœRI-positive patients are recognized by a combination of autologous serum skin testing and evoked histamine release from basophils of normal human donors. Autoantibody-positive and -negative patients are clinically indistinguishable and are treated routinely by combinations of H₁ and occasionally H₂-antihistamines in both cases. However, severely affected patients who are anti-FcœRI-positive can also be treated by non-specific immunotherapy (plasma pheresis, intravenous immunoglobulin, cyclosporin.     

Hypersensitivity reactions to anti-SARS-CoV-2 vaccines: Basophil reactivity to excipients

Basophil activation test (BAT) can tackle multiple mechanisms underlying acute and delayed hypersensitivity to drugs and vaccines and might complement conventional allergy diagnostics but its role in anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine-related hypersensitivity is ill-defined. Therefore, 89 patients with possible hypersensitivity (56 % with delayed mucocutaneous manifestations) to anti-SARS-CoV-2 vaccines were tested with BAT for Macrogol 3350, DMG-PEG 2000, PEG 20000, polysorbate-80 and trometamol and compared to 156 subjects undergoing pre-vaccine BAT. A positive BAT was associated with delayed reaction onset (p = 0.010) and resolution (p = 0.011). BAT was more frequently positive to DMG-PEG 2000 than to other excipients in both groups (p < 0.001). DMG-PEG 2000 reactivity was less frequent in vaccine-naïve (6 %) than vaccinated subjects (35 %, p < 0.001) and associated with mRNA-1273 vaccination. DMG-PEG 2000 BAT might therefore have a diagnostic role in subjects with delayed hypersensitivity reactions. Natural immunity might be a key player in basophil activation.