Journal
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
Volume 140, Issue 3, Pages 750-+Publisher
MOSBY-ELSEVIER
DOI: 10.1016/j.jaci.2016.12.989
Keywords
Anaphylaxis; basophils; CD63 activation; Fc epsilon RI expression; CCL2; serum tryptase
Categories
Funding
- Slovenian Research Agency [P3-0360]
- Clinician Scientist award - UK Medical Research Council [MR/K010468/1]
- European Union [312147]
- UK Medical Research Council [WM/3306381]
- National Institute for Health Research (NIHR) Biomedical Research Centre based at Imperial College Healthcare NHS Trust
- Imperial College London
- MRC [MR/K010468/1] Funding Source: UKRI
- Asthma UK [MRC-AsthmaUKCentre, MRC-Asthma UK Centre] Funding Source: researchfish
- Medical Research Council [G1000758, MR/K010468/1, G1000758B] Funding Source: researchfish
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Background: The role of basophils in anaphylaxis is unclear. Objective: We sought to investigate whether basophils have an important role in human anaphylaxis. Methods: In an emergency department study we recruited 31 patients with acute anaphylaxis, predominantly to Hymenoptera venom. We measured expression of basophil activation markers (CD63 and CD203c); the absolute number of circulating basophils; whole-blood FCER1A, carboxypeptidase A3 (CPA3), and L-histidine decarboxylase (HDC) gene expression; and serum markers (CCL2, CCL5, CCL11, IL-3, and thymic stromal lymphopoietin) at 3 time points (ie, during the anaphylactic episode and in convalescent samples 7 and 30 days later). We recruited 134 patients with Hymenoptera allergy and 76 healthy control subjects for comparison. We then investigated whether the changes observed during venom-related anaphylaxis also occur during allergic reactions to food in 22 patients with peanut allergy undergoing double-blind, placebo-controlled food challenge to peanut. Results: The number of circulating basophils was significantly lower during anaphylaxis (median, 3.5 cells/mu L) than 7 and 30 days later (17.5 and 24.7 cells/mu L, P < .0001) and compared with those in patients with venom allergy and healthy control subjects (21 and 23.4 cells/mu L, P < .0001). FCER1A expression during anaphylaxis was also significantly lower than in convalescent samples (P <= .002) and control subjects with venom allergy (P < .0001). CCL2 levels (but not those of other serum markers) were significantly higher during anaphylaxis (median, 658 pg/mL) than in convalescent samples (314 and 311 pg/mL at 7 and 30 days, P < .001). Peanut-induced allergic reactions resulted in a significant decrease in circulating basophil counts compared with those in prechallenge samples (P = .016), a decrease in FCER1A expression (P = .007), and an increase in CCL2 levels (P = .003). Conclusions: Our findings imply an important and specific role for basophils in the pathophysiology of human anaphylaxis.
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