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The Journal of allergy and clinical immunology

Basophil expression of diamine oxidase: a novel biomarker of allergen immunotherapy response.


PMID 25457150

Abstract

Immunotherapy inhibits basophil histamine release, but the assay is cumbersome, and no one has studied the effects of immunotherapy withdrawal. Intracellular fluorochrome-labeled diamine oxidase (DAO) was used as a novel functional readout of basophil histamine release after immunotherapy. Results were compared with conventional basophil surface expression of activation markers. Subcutaneous immunotherapy (SCIT)-treated patients (nxa0= 14), sublingual immunotherapy (SLIT)-treated patients (nxa0= 12), participants who completed 3 years of treatment with grass pollen sublingual immunotherapy (the SLIT-TOL group; nxa0= 6), patients with untreated seasonal allergic rhinitis (SAR; nxa0= 24), and nonatopic control subjects (nxa0= 12) were studied. Intracellularly labeled DAO(+) and surface expression of CD203c(bright), CD63(+), and CD107a(+) on chemoattractant receptor-homologous molecule expressed on TH2 lymphocytes (CRTh2)-positive basophils were measured by means of flow cytometry. Serum IgG4 levels and serum inhibitory activity for IgE-allergen complex binding to B cells (IgE-FAB) and basophil histamine release were also determined. Proportions of allergen-stimulated DAO(+)CRTh2(+) basophils were higher in participants in the SCIT, SLIT, and SLIT-TOL groups (all Pxa0< .0001) compared with those in patients in the SAR group. Similarly, there were lower proportions of CRTh2(+) basophils expressing surface CD203c(bright) (all Pxa0< .001), CD63 (all Pxa0< .001), and CD107a (allxa0Pxa0< .01). Rhinitis symptoms were lower in the SCIT, SLIT, and SLIT-TOL groups (Pxa0< .001) compared with those in the SAR group. Serum inhibitory activity for IgE-FAB and basophil histamine release were also significantly greater in all immunotherapy groups (Pxa0< .05) compared with the SAR group. These results support long-term clinical and immunologic tolerance during and after grass pollen immunotherapy. Intracellularly labeled DAO expression by basophils merits further investigation as a surrogate biomarker for monitoring efficacy and tolerance after immunotherapy.

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