Basophil activation as a measure of allergic response
S.G.O. Johansson
Department of Medicine, Clinical Immunology and Allergy Unit, Karolinska Institute and
Department of Clinical Immunology and Transfusion Medicine, Karolinska University
Hospital, Stockholm, Sweden.
In IgE-mediated allergy tissue mast-cells and basophils in blood are sensitized with IgE
antibodies against the allergen to which the individual reacts. By stimulating the basophils in
vitro with decreasing doses of the allergen, the allergen sensitivity of the cells can be
determined. Cell response can be measured by e.g. histamine release or up-regulation of
markers like CD203c or CD63 measured by flow cytometry. Basophil allergen threshold
sensitivity based on CD63 has been called CD-sens (1). Basophil response at one or a few
high doses of allergen is a measure of cell reactivity and not allergen sensitivity (2). Patients
can have the same CD-sens but differ significantly in cell reactivity (Figure 1).
CD-sens for measurement of an individual’s allergen sensitivity has been compared to
conventional, diagnostic methods. Thus, a significant correlation (r=0.50; p<0.01) was
obtained with skin prick titration (3), nasal allergen titration provocation (r=0.54; p<0.05) in
allergic rhinoconjunctivitis (3) and inhalation provocation (p=0.52; p<0.01) in allergic asthma
(4). Interestingly, in patients with a moderate or low bronchial hyper-reactivity the correlation
was excellent (r=0.88; p<0.0001). Oral DBPCFC of peanut allergic children showed an
excellent correlation between a positive provocation and CD-sens and in no case was CD-sens
negative and the DBPCFC positive (5). No correlation was, in any of the studies, found
between the results of the established diagnostic test for sensitivity and basophil reactivity.
In patients that have been treated with allergen specific immunotherapy, ASIT, performing
CD-sens on buffy coat washed in saline results in a higher CD-sens value. Less allergen is
needed to stimulate the basophils (Figure 2) indicating that a factor in plasma, called allergen
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binding activity, ABA, is blocking the allergen’s access to the sensitized inflammatory cells.
ABA is increasing during ASIT (6) and seems to be a measure of ASIT success.
Together these results suggest that CD-sens not only is reflecting the degree of IgEsensitization, but also provides a common denominator that can monitor the allergen
sensitivity of the respective target organ. It is conceivable, that these circulating IgEsensitized basophils are more closely associated with the local, target organ response than is
for example the level of serum IgE antibodies by itself.
References
1. Johansson SGO, Nopp A, van Hage M, Olofsson N, Lundahl J, Wehlin L, Söderström
L, Stiller V, Öman H. Passive IgE-sensitization by blood transfusion. Allergy
2005;60:1192-1199.
2. Kleine-Tebbe J, Erdmann S, Knol EF, MacGlashan DW, Poulsen L, Gibbs B.
Diagnostic tests based human basophils: Potentials, pitfalls and perspectives. Int Arch
Allergy Clin Immunol 2006;141:79-90.
3. Nopp A, Johansson SGO, Ankerst J, Bylin G, Cardell LO, Grönneberg R, Irander K,
Palmqvist M, Öman H. Basophil allergen threshold sensitivity. A useful approach to
anti-IgE treatment efficacy evaluation. Allergy 2006;61:298-302.
4. Dahlen B, Nopp A, Johansson SGO, Eduards M, Skedinger M, Adedoyin J. Basophil
allergen threshold sensitivity, CD-sens, is a measure of allergen sensitivity in asthma.
Clin Exp Allergy. 2011;41:1091-1097.
5. Glaumann S, Nopp A, Johansson SGO, Rudengren M, Bores MP, Nilsson C. Basophil
allergen threshold sensitivity, CD-sens, IgE-sensitization abd DBPCFC in peanutsensitized children. Allergy 2011, in press.
6. Nopp A, Cardell LO, Johansson SGO, Öman H. CD-sens, a useful tool for optimizing
allergen dosage during initiation of ASIT. A pilot study. Allergy 2009;64:811-814.
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