Basophils, high-affinity IgE receptors, and CCL2 in human anaphylaxis

Abstract

BackgroundThe role of basophils in anaphylaxis is unclear.ObjectiveWe sought to investigate whether basophils have an important role in human anaphylaxis.MethodsIn 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.ResultsThe number of circulating basophils was significantly lower during anaphylaxis (median, 3.5 cells/μL) than 7 and 30 days later (17.5 and 24.7 cells/μL, P < .0001) and compared with those in patients with venom allergy and healthy control subjects (21 and 23.4 cells/μL, 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).ConclusionsOur findings imply an important and specific role for basophils in the pathophysiology of human anaphylaxis.

Human mast cells and basophils—How are they similar how are they different?

“…As discussed earlier, basophils readily migrate from the blood to many different other tissues affected by allergic inflammation and this is accompanied by a reduction in circulating basophils . More recently, a rapid reduction in blood basophils was reported for patients with insect venom anaphylaxis and also for peanut allergic patients undergoing oral food challenges . The reduction in circulating basophils inversely correlated with CCL2 levels, a chemokine which is released by human mast cells and may indicate an important link between these two effector cells and anaphylaxis.…”

“…There is preliminary evidence that basophils can also have anti‐inflammatory properties as shown in a model of skin hypersensitivity . It is still unclear whether circulating basophils play a role in human anaphylaxis …”

The pathophysiology of anaphylaxis

“…This includes tryptase, 64, 80, 137-139 prostaglandins 132, 137 and cytokines/chemokines. 65, 138 Depletion of the bradykinin precursor, high molecular weight kininogen, has been observed in anaphylaxis, likely through activation of the plasma contact system and kallakrein. 64, 140, 141 Anaphylaxis patients may also experience depletion of clotting factors, including Factors V and VIII, and in extreme cases develop diffuse intravascular coagulation.…”

Important and specific role for basophils in acute allergic reactions

“…Consequently, two studies which investigated the role of basophils in human anaphylaxis (after insect sting or food challenge), involved only a very limited number of patients who experienced severe reactions after challenge . However, studies in the challenge setting do have the advantage of allowing comparison with prereaction samples, optimal sampling and controlling potentially confounding factors (including acute treatment, where blood samples can often be taken prior to treatment) …”

“…Corticosteroids have broad immunological effects, albeit much delayed compared to other anti‐allergic therapies. With respect to basophils, corticosteroids inhibit their pro‐allergic functions, and this might be an important confounder.…”