INTRODUCTION:

Diamine oxidase (DAO) catabolizes and inactivates histamine, a key player in a wide range of invalidating conditions, such as migraine and chronic spontaneous urticaria (CSU). The highest expression of DAO occurs in the gastrointestinal tract, possibly to control the burden of histamine intake from food.

METHODS:

Here, we tested the hypothesis that a 30-day oral supplementation with DAO (1 capsule b.i.d., 15 min before a meal) could reduce the severity of CSU as estimated by the 7-Day Urticaria Activity Score (UAS-7). The study was designed as a double-blind, placebo-controlled, crossover investigation of 22 patients with CSU incompletely controlled by first-line antihistamine therapy.

RESULTS:

Twenty patients completed the study. Supplemental therapy with DAO caused a 3.8 ± 1.2 point mean ± SEM UAS-7 score reduction in patients with low serum DAO levels at time 0 (p = 0.041 compared to placebo). The degree of UAS-7 improvement was inversely correlated with the levels of basal DAO (p = 0.019). Patients receiving DAO supplementation were able to slightly reduce their daily antihistamine dose (p = 0.049).

CONCLUSION:

These data suggest that DAO may be involved in the pathogenic cascade of CSU and that DAO supplementation could be effective for symptom relief in patients with low DAO levels in serum.

© 2018 S. Karger AG, Basel.

BACKGROUND:

Histamine intolerance is thought to trigger manifold clinical symptoms after ingesting histamine-rich food due to reduced activity of diamine oxidase (DAO). No study has hitherto systematically assessed daily fluctuations of histamine levels and DAO activities in symptomatic patients. The aim of the study was to investigate the presence of histamine intolerance, to therefore establish day profiles of histamine levels and DAO activities, and to compare the results between patients with suspected histamine intolerance, food allergy and healthy controls.

METHODS:

We determined day profiles of histamine plasma levels and DAO serum activities in 33 patients with suspected histamine intolerance, in 21 patients with proven food allergy and in 10 healthy control patients. Clinical symptoms, food intolerances and further clinical and laboratory chemical parameters were evaluated.

RESULTS:

Twenty-four percent (8 of 33) suspected histamine-intolerant patients showed elevated histamine levels during the day. That might be caused by constantly and significantly reduced DAO activities in these patients compared to food-allergic and control patients. The remaining 25 patients presented normal histamine levels and DAO activities, but an increased prevalence of multiple food intolerances compared to the other subgroup of suspected histamine-intolerants. There was no correlation between subjective complaints and serological histamine parameters in patients with suspected histamine intolerance.

CONCLUSIONS:

We determined by daily profiling that decreased DAO activities correlated with elevated histamine levels in a subgroup of suspected histamine-intolerants. This finding discriminates these patients from food intolerant individuals with similar clinical symptoms and strongly suggests the presence of histamine intolerance.

© 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

OBJECTIVE:

Recently we characterized five mouse monoclonal antibodies that allow the specific and sensitive detection of human diamine oxidase (DAO). To understand differences in binding characteristics and recognition of enzyme variants, we mapped the antibody binding sites.

METHODS:

Fragments of human DAO were expressed as glutathione-S-transferase fusion proteins that were used for testing antibody binding on immunoblots. Combined information from species cross-reactivity, sequence comparison and binding site-prediction software were used to localize the epitope recognized by each antibody.

RESULTS:

All five monoclonal DAO antibodies bound to linear epitopes between the N3 and enzymatic domains of the 732 amino acid protein. The binding sites could be mapped onto amino acid regions V²⁶²-E²⁷⁸ and P²⁷⁹-R²⁸⁸, respectively, which exhibit considerable sequence variation in mammals explaining the fact that the human DAO antibodies do not cross-react with DAO from other species. The antibodies efficiently bind only denatured human DAO but not the native protein.

CONCLUSIONS:

Characterization of the binding sites of the DAO antibodies revealed that the antibodies bind two adjacent epitopes and exhibit similar binding characteristics and species cross-reactivity. As the epitopes do not overlap any of the amino acid substitutions described for clinically significant DAO gene polymorphisms, our antibodies will also be useful for analyses of the mutant DAO proteins.