Basal Serum Diamine Oxidase Levels as a Biomarker of Histamine Intolerance: A Retrospective Cohort Study.

Background: Histamine Intolerance (HIT) is a multifaceted pseudoallergic disorder possibly due to defective histamine metabolism. Diamine oxidase (DAO) contributes to histamine degradation and can be measured in the serum. The role of DAO measurement in the diagnostic work-up of HIT still remains unclear, and conflicting results have been reported in the literature. Therefore, we aimed to evaluate the possible clinical usefulness and consistency of DAO value ranges as provided by the assay manufacturer and verify whether they could predict the response to treatment. Methods: We retrospectively analyzed 192 outpatients with HIT symptoms and measured serum DAO values at baseline. Patients were prescribed either with low-histamine diet and/or enzymatic supplementation according to symptom severity and re-evaluated six to eight months later. Patients were stratified into three groups according to DAO levels: <3 U/mL, 3−10 U/mL, and >10 U/mL. HIT severity was assessed on a scale of 1 to 5 before and after treatment. Results: A total of 146 patients completed the study. Gastrointestinal and cutaneous symptoms, often associated with headache, were more frequent in subjects with DAO < 10 U/mL. Symptom severity and DAO ranges were correlated. Patients with intermediate DAO levels (3−10 U/mL) showed a more complex clinical phenotype but also a more significant improvement in symptom severity (score reduction 50%, interquartile range (IQR) = 33−60%) when compared to patients with low DAO (40%, IQR = 20−60%; p = 0.045) or high DAO (33%, IQR = 0−50%; p < 0.001). Complex clinical phenotypes were also more frequent in patients with intermediate DAO levels. Conclusions: HIT is characterized by typical symptoms and low levels of DAO activity. Symptom severity was associated with the degree of DAO deficiency. Patients with DAO values between 3 and 10 U/mL show the best response to treatment (low-histamine diet and/or DAO supplementation). DAO value could arguably be considered as a predictor of clinical response to treatment. Prospective studies are needed to confirm these data.

Diamine Oxidase Supplementation in Chronic Spontaneous Urticaria: A Randomized, Double-Blind Placebo-Controlled Study.

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.

Effect of sublingual immunotherapy with grass monomeric allergoid on allergen-specific T-cell proliferation and interleukin 10 production.

BACKGROUND: Sublingual immunotherapy (SLIT) is safe and efficacious in the treatment of patients with allergic rhinitis. Although favorable clinical effects have been observed with controlled trials as early as a few months since the beginning of treatment, few biological changes induced by SLIT have been demonstrated. OBJECTIVE: To investigate in grass-allergic patients the effect of a 2-month SLIT regimen, administered with a simplified protocol without up-dosing, on proliferation and production of cytokines characteristic of the regulatory T-cell phenotype (interleukin 10 [IL-10] and transforming growth factor beta [TGF-beta]) by allergen-specific T cells. METHODS: Patients were recruited to the study in January 2006. SLIT was performed by self-administration and was continued for 60 days from February to April 2006. Eleven grass pollen-allergic patients with seasonal rhinitis were treated daily before the pollen season for 2 months with a modified allergen (monomeric allergoid) derived from a 3-grass pollen extract. Allergen-specific proliferation and production of IL-10 and TGF-beta were measured on peripheral blood mononuclear cells at baseline and treatment end. Tetanus toxoid served as the control antigen. RESULTS: After SLIT, allergen-specific (P = .002) but not tetanus toxoid-specific proliferation decreased, whereas IL-10 transcription increased (P < .001). TGB-beta transcription was also increased after treatment, although not statistically significantly (P = .06). Changes in proliferation to allergen and in IL-10 transcription were correlated (r = -0.82, P = .003). CONCLUSIONS: A short-term course of SLIT with modified allergen in grass-allergic patients is associated with the reduction of allergen-specific proliferation and with the up-regulation of the IL-10 regulatory cytokine.

Platinum group elements enhance the allergic immune response by acting on dendritic cells.

BACKGROUND: Atmospheric pollution may play a role in the immune response to allergens either directly or by entering the food chain. While particulate platinum group elements (PLGE) emitted by catalytic converters can be considered biologically inert, approximately 10% of these species accumulate in the environment as bioavailable soluble forms. METHODS: We challenged in vitro human immature and mature monocyte-derived dendritic cells with subtoxic concentrations of soluble species of PLGE. Dendritic cells were studied both at baseline and following treatment with Na(2)PtCl(6), Na(2)PdCl(6) or Na(3)RhCl(6). (NH(4))(6)Mo(7)O(24) was included as control. The following end-points were considered: expression of differentiation markers, effectiveness of allergen presentation and Th2 cytokine production by cocultured T lymphocytes, expression of IgE-type I receptor and efficiency of IgE-dependent endocytosis. RESULTS: We found that treatment with PLGE (but not with the control metal) increased costimulatory molecule expression and antigen presentation, amplified IL-5 production by cocultured T lymphocytes, upregulated IgE-type I receptor membrane expression, and augmented IgE-type I receptor-mediated endocytosis. CONCLUSIONS: We conclude that PLGE have an adjuvant-like effect on dendritic cells that can favor and amplify the immune response to allergens.