Is there a rationale for supplementing with vitamin D patients under treatment with allergen immunotherapy?

Vitamin D (VD) has been shown to exert immunomodulatory activities, especially in promoting immune tolerance. For these properties VD has been proposed in the therapy of immunological conditions in which the loss of tolerance is the key pathogenetic aspect of the disease, such as allergies. Despite these properties available literature suggests VD is not useful in treating or preventing allergic diseases and whether low serum VD levels favor allergic sensitization and severity is debated. The level of VD is one of the many conditions that can influence allergic sensitization and therefore only a multivariate analysis on a numerically adequate cohort of patients, that considers all the factors that can favor allergy, would be able to assign the weight of each variable and determine the extent to which VD inhibits allergic sensitization and march. On the contrary, VD is able to potentiate the antigen-specific tolerogenic response induced by Allergen Immunotherapy (AIT) as demonstrated by the large majority of studies. In our experience, the association of VD and Sublingual AIT (LAIS, Lofarma, Italy) gave an excellent clinical and immune response in particular enhancing the differentiation of memory T regulatory cells. While waiting for a more extensive literature, VD/AIT combination should be always performed in treating allergies. In any case, the assessment of the level of VD should become a routine in allergic patients with an indication to AIT as, in case of VD deficiency or insufficiency, VD seems a particularly active adjuvant to the immune treatment.

Allergic patients treated with allergen immunotherapy benefit from the simultaneous administration of Vitamin D, which on the contrary does not offer benefits when used alone for the prevention or treatment of allergies. Vitamin serum levels should be always evaluated in patients treated with allergen immunotherapy because these patients have the maximum clinical and immunological benefit from simultaneous vitamin D supplementation.

Real-Life Effectiveness of Subcutaneous Immune Therapy with Carbamylated Monomeric Allergoids on Mite, Grass, and Pellitory Respiratory Allergy: A Retrospective Study.

Background: real-life studies are encouraged to evaluate the effectiveness and safety of allergen immunotherapy (AIT). In this context, a retrospective cohort study was conducted to assess the effectiveness and safety of carbamylated monomeric allergoid subcutaneous immunotherapy (MA-SCIT), along with patient satisfaction. Methods: a total of 291 patients with rhinoconjunctivitis with or without asthma with inhalant (house dust mite, grass, and pellitory) allergies were enrolled in this study. Perceived efficacy and perceived satisfaction with MA-SCIT, symptom score by VAS, ARIA classification of rhinitis, drug consumption, number of asthma worsening episodes, and asthma symptom control were evaluated by questionnaires before, after one year, at the end of treatment, and after one or two years of MA-SCIT. Results: the overall symptom score significantly decreased over the years of MA-SCIT, irrespective of specific sensitization (p < 0.01). There was a substantial amelioration of rhinitis severity, with a significant reduction (p < 0.01) in drug use. A significant reduction was observed in the asthma symptom VAS score and asthma-worsening episodes requiring systemic steroids. None of the patients reported any severe adverse reactions. Finally, 90% of the patients reported full satisfaction with the treatment. Conclusions: the study showed that AIT with carbamylated monomeric allergoids of grass, pellitory, and mites was effective and well tolerated by patients.

AllergoOncology: Role of immune cells and immune proteins.

BACKGROUND: Immune cells and immune proteins play a pivotal role in host responses to pathogens, allergens and cancer. Understanding the crosstalk between allergic response and cancer, immune surveillance, immunomodulation, role of immunoglobulin E (IgE)-mediated functions and help to develop novel therapeutic strategies. Allergy and oncology show two opposite scenarios: whereas immune tolerance is desired in allergy, it is detrimental in cancer. AIM: The current review provides an update on the role of immune cells and immune proteins in allergy and cancer fields. METHODS: Authors investigated the role of relevant immunological markers and the correlation with cancer progression or cancer suppression. RESULTS: Activated immune cells such as macrophages 'M1', dendritic cells (DCs), innate lymphoid cells (ILC2), NK cells, Th1, follicular T helper cells (TFH), TCD8+, B lymphocytes and eosinophils have inhibitory effects on tumourigenesis, while tolerogenic cells such as macrophages 'M2,' tolerogenic DCs, ILC3, T and B regulatory lymphocytes appear to favour carcinogenesis. Mastocytes and alarmins can have both effects. RIgE antibodies and CCCL5 chemokine have an anticancer role, whereas IgG4, free light chains, Il-10, TGF-ß, lipocalin-2, CCL1 chemokine promote cancer progression. Fundamental is also the contribution of epigenetic changes regulated by the microRNA in cancer progression. CONCLUSION: This knowledge represents the key to developing new anticancer therapies.

Vernal Keratoconjunctivitis: A Case of Anti-IgE Treatment with Short-Lasting Remission.

Vernal keratoconjunctivitis (VKC) is a persistent, severe allergic eye disease, mainly occurring in children, that can lead to severe ocular complications including visual loss. The underlying etiology and pathophysiology of VKC remain unclear. Common therapies include topical antihistamines and mast cell stabilizers that are effective in mild-to-moderate forms of VKC but are often ineffective in severe forms that require topical or systemic corticosteroids. Dependence on steroids is common with potential adverse effects both local, as increased intraocular pressure, glaucoma, infection and cataract, as well as systemic ones, as reduction in child growth velocity. Alternative therapies are immunosuppressive drugs, like cyclosporine A and tacrolimus, that usually are effective but may also cause adverse effects. A promising therapeutic option is omalizumab, a recombinant anti-IgE humanized monoclonal antibody, currently used as add-on therapy for moderate to severe uncontrolled allergic asthma and chronic spontaneous urticaria. Here, we report the short-time duration of effective relief of symptoms after the prolonged use of omalizumab in a patient affected by refractory VKC. However, in our case any apparent beneficial effect was short lasting, and we propose that the duration of the disease and the concomitant long-term use of steroids leads to iatrogenic damage; thus, the disease becomes refractory to anti-IgE treatment.

Nanoparticle-based immunotherapy: state of the art and future perspectives.

INTRODUCTION: For several years now, medicine has been benefiting from the contribution of nanoparticles (NPs) technology for both diagnosis and therapy. They can be used as adjuvants, being capable per se of immune-modulating activity, or as carriers for molecules to be transported to a specific target, eventually loaded with specific ligands favoring specific uptake. AREAS COVERED: The review focuses on experimental use of NPs as adjuvants/carriers for allergen immunotherapy (AIT). Human clinical trials conducted so far are discussed. EXPERT OPINION: Results of experimental studies and recent clinical trials support the use of NPs as carrier/adjuvant in AIT. Comparisons between NP-based and classical AIT are needed, to show the usefulness of the NP-based approach. However, there are still unsolved problems: the persistence of non-degradable NPs with possible toxicological consequences, and the formation of the protein corona around the NPs, which could alter their activity and fate. Virus-like particles seem the most promising NPs for allergy treatment, as for other vaccines. Over the next decade, NP-based AIT will be largely used to treat allergic disorders.

Omalizumab in chronic spontaneous urticaria: steroid sparing effect.

Omalizumab has been recognized to be effective in the treatment of chronic spontaneous urticaria (CSU). The Italian Medicines Agency authorizes two omalizumab courses, only for patients with CSU unresponsive to antihistamines, and this schedule may limit omalizumab use. Unfortunately, in the majority of CSU, the schedule is unsatisfactory because symptoms usually recur shortly after discontinuation of treatment. A case of a patient needing more than two treatment courses with omalizumab is reported, in order to discuss the rationale for its long-term use. Patient had needed systemic steroids almost continuously for 4 years. Two severe glucocorticoid-associated adverse events (GAEs) occurred during long-term treatment. Omalizumab 300 mg monthly was started with immediate disappearance of the urticarial lesions. Beneficial effects waned shortly after discontinuation of treatment, and further steroid use was needed. A second omalizumab course showed the same clinical pattern, with prompt response and recurrence of symptoms after suspension. Therefore, we decided to repeat the 6 months omalizumab treatment as soon as symptoms recurred, to avoid further emergency steroid treatments and GAEs. This experience suggests that long-term use of omalizumab could be useful. Evidences show that omalizumab is effective and safe for re-treatment and long-term use of responding patients after recurrence.

Fluticasone/formoterol association favors long-lasting decrease in bronchial reactivity to methacholine and weekly PEF variability.

Inhaled corticosteroids (ICS)/long-acting beta-agonists (LABA) association offers a better asthma control than a higher steroid dose with short-acting beta-agonists as needed. In this study, we evaluated the effect of the association on bronchial hyperreactivity (BHR) and peak expiratory flow (PEF) variability, as such parameters are positively correlated with increased asthma morbidity and exacerbations. Thirty-six adult patients with mild persistent asthma were enrolled. After a 7-day run-in, they were randomly assigned to three therapy regimens for 6 weeks: Group 1, fluticasone 125 µg + formoterol 5 µg in the same device; Group 2, fluticasone 125 µg + formoterol 12 µg as needed; Group 3, fluticasone 250 µg + formoterol 12 µg as needed. We evaluated changes induced in weekly PEF variability (measured during the entire study and 4 weeks of follow-up) and pre- and post-study PD20 methacholine (MCH). Weekly PEF variability decreased in all groups during treatment with the greatest reduction in Group 1, followed by Group 3, and finally Group 2. During the follow-up, no significant changes were detected in Group 1, whereas a trend towards an increased variability was found in Groups 2 and 3. Post-treatment PD20 MCH was significantly higher versus the pre-treatment. The increase observed in Group 1 was significantly higher compared to Groups 2 and 3 and that observed in Group 3 in respect to Group 2. The study proves that both BHR and PEF variability are influenced by ICS. This effect was greater with fluticasone/formoterol association compared to fluticasone alone with formoterol as needed even at higher steroid dose.