Patient on allergen immunotherapy developed systemic lupus erythematosus?– A clinico-pharmacological look out

Drug induced lupus is an autoimmune condition secondary to drug exposure which leads to development of systemic lupus erythematosus (SLE). However, labelling the culprit drug needs a prudent insight into the pharmacological plausibility of each of the offending drugs in suspicion. Here we present a report where allergen immunotherapy was suspected to cause SLE and a deeper clinico-pharmacological evaluation cleared the air.

Allergen Immunotherapy: Current and Future Trends

Allergen immunotherapy (AIT) is the sole disease-modifying treatment for allergic rhinitis; it prevents rhinitis from progressing to asthma and lowers medication use. AIT against mites, insect venom, and certain kinds of pollen is effective. The mechanism of action of AIT is based on inducing immunological tolerance characterized by increased IL-10, TGF-β, and IgG4 levels and Treg cell counts. However, AIT requires prolonged schemes of administration and is sometimes associated with adverse reactions. Over the last decade, novel forms of AIT have been developed, focused on better allergen identification, structural modifications to preserve epitopes for B or T cells, post-traductional alteration through chemical processes, and the addition of adjuvants. These modified allergens induce clinical-immunological effects similar to those mentioned above, increasing the tolerance to other related allergens but with fewer side effects. Clinical studies have shown that molecular AIT is efficient in treating grass and birch allergies. This article reviews the possibility of a new AIT to improve the treatment of allergic illness.

Impulsive simulation model for the dynamics of allergen immunotherapy

This study aims to analyze the effects of allergen immunotherapy, used to treat allergic symptoms such as pollen allergy. Mathematical models are used as a methodological approach to simulate from a system of impulsive differential equations the dynamics of the model. Immunotherapy is based of supplying small amounts of pollen to the patient, which leads to minimizing severe allergic symptoms when patients are subsequently exposed to higher amounts of pollen in the environment. Lymphocyte concentrations are considered state variables, allowing the behavior and efficacy of allergen immunotherapy to be identified. The manuscript proposes a method that allows to model mixed systems. Phenomena that present continuous times in some instants and discrete times in others, these are phenomena that are frequently found in the field of physics. Allergen immunotherapy is most effective when a treatment is created with pollen dose increments in a linear form.

The Potential of Exosomes in Allergy Immunotherapy

Allergic diseases represent a global health and economic burden of increasing significance. The lack of disease-modifying therapies besides specific allergen immunotherapy (AIT) which is not available for all types of allergies, necessitates the study of novel therapeutic approaches. Exosomes are small endosome-derived vesicles delivering cargo between cells and thus allowing inter-cellular communication. Since immune cells make use of exosomes to boost, deviate, or suppress immune responses, exosomes are intriguing candidates for immunotherapy. Here, we review the role of exosomes in allergic sensitization and inflammation and we discuss the mechanisms by which exosomes could be used in immunotherapeutic approaches for the treatment of allergic diseases. We propose the following approaches: a) Mast cell derived exosomes expressing IgE receptor FcεRI could absorb IgE and down-regulate systemic IgE levels. b) Tolerogenic exosomes could suppress allergic immune responses via induction of regulatory T cells. c) Exosomes could promote TH1-like responses towards an allergen. d) Exosomes could modulate IgE-facilitated antigen presentation.

Standardized Quantitative Evaluation of Clinical Effectiveness and Side Effect Profile of Subcutaneous and Sublingual Allergen-Specific Immunotherapy in Children: A 5-Year Single Center Experience

Objective: Allergen-specific immunotherapy (allergen-SIT) is a treatment method with variable efficacy in allergic diseases. This study aimed to investigate the effectiveness of allergen immunotherapy, frequency of LRs and SRs and variables affecting these parameters in patients who underwent allergen-SIT. Materials and Methods: In this study, the recorded data of 81 patients, who received subcutaneous (SCIT) or sublingual (SLIT) allergen immunotherapy for respiratory allergic diseases between 2014 and 2019, were analyzed. In asthma and/or allergic rhinoconjunctivitis (ARC) patients, the effectiveness of treatment was evaluated by analysing the change rates in disease symptom, medication and combined scores (symptom + medication) and visual analog score (VAS). Treatment success was defined by the degree of decrease in scores as; high response above 50%; low response between 20-50%; and failure <20%.Results: The mean age of allergen-SIT initiation was 11.4± 3.1 years. Diagnostic distributions of the patients were asthma (± ARC) in 64.2%, and ARC (without asthma) in 35.8%. The mode of allergen-SIT was SCIT in 77.8% (65% asthma and 35% ARC) and SLIT in 22.2% (61.1% asthma and 38.9% ARC). The main allergens used in allergen-SIT were mite (79%), grass-grain pollen (33.3%), alternaria (9.9%) and olea (8.6%). There was a significant decrease in symptoms, medication, combined and VAS scores in the asthma and ARC groups (p <0.0001), when end-SCIT values were compared to baseline. SLIT also resulted in significant decreases in these scores except asthma medication score. Among the asthma patients the rate of high-responders was 88.8% by SCIT and 50% by SLIT, according to combined asthma score. Among the ARC (without asthma) patients the rate of high-responders was 100% for both SCIT and SLIT. SCIT resulted in local (LR) and systemic side effects (SR) in 18% and 0.6% (all Grade I and Grade II) of the total injections performed. A high number of total injections was significantly associated with higher LR and SR rates. While LR was observed in 16.6% of the patients who underwent SLIT, no systemic reaction was found in any of the patients. Conclusion: SCIT was highly successful in the treatment of asthma and ARC in terms of the degree of therapeutic response. SLIT resulted in a high rate of good response in ARC patients, but a lower response degree in asthmatic patients. Systemic side effects were very low as a result of close risk monitoring and the dose adjustments performed. Keywords: Allergen-specific immunotherapy, SCIT, SLIT, efficacy, symptom score, medication score, visual analog score, side effects

Impact of house dust mite-driven asthma on children’s school performance and activity

Evidence regarding asthma’s impact on children’s daily lives is limited. This prospective and cross-sectional, observational, multicenter study assessed school/work and activity impairment in children and adolescents with allergic asthma and their caregivers and allergen immunotherapy (AIT) effects. Included patients were schooled children and adolescents (5 to 17 years) with allergic asthma due to house dust mites (HDM). Impairment of school/work (i.e., absenteeism and presenteeism) and activity was measured in patients and their caregivers using the Work Productivity Impairment Questionnaire plus Classroom Impairment Questions: Allergy Specific (WPAI + CIQ:AS). HDM allergic patients with school impairment received subcutaneous AIT with a MicroCrystalline Tyrosine-associated allergoid. WPAI + CIQ:AS and effectiveness variables were compared between baseline and 1-year post-AIT. Of the 113 patients included, 59 (52.2%) and 51 (45.1%) showed school and activity impairment, respectively, missing a mean (SD) of 37.6 (24.4) % and 42.6 (25.6) % of school and activity time, respectively. Twenty-six (23%) caregivers reported activity impairment and, of the 79 (69.9%) employed, 30 (38%) reported work impairment. Of the 65 patients with school/activities impairment, 41 (63.1%) received AIT, of which 21 (51.2%) completed 1 year of treatment. Effectiveness variables and WPAI + CIQ:AS significantly improved: Mean (SD) school impairment decreased from 39.7 (26.7) to 2.1 (7.1) % (p < 0.001) and activity impairment from 46.2 (34.6) to 1.4 (3.6) % (p < 0.001).Conclusion: Allergic asthma due to HDMs results in school/work and activity impairment in children and adolescents and their caregivers. One year of AIT provided clinical benefits and reduced school and activity impairment. What is Known:• Allergic asthma impairs children’s school performance and daily activities.• Allergen immunotherapy modifies allergic disease course and ameliorates its symptoms. What is New:• Asthma symptoms due to allergy to house dust mites impair children’s school attendance and productivity and daily activity and their caregivers’ work performance and daily lives.• Allergen immunotherapy with a house dust mite MicroCrystalline Tyrosine (MCT)-associated allergoid seems to provide clinical benefits, associated with decreased school and activity impairment, supporting it as an effective treatment option.

Allergen-Specific IgE and IgG4 as Biomarkers for Immunologic Changes during Subcutaneous Allergen Immunotherapy

(1) Background: Biomarkers of efficacy for subcutaneous immunotherapy (SCIT) on allergic rhinitis have not been evaluated in details. The present study aims to assess the relevance of measuring of sIgE, sIgG4 and IgE/IgG4 ratio during SCIT in patients with allergic rhinitis; (2) Methods: 20 patients, 13 men and 7 women aged 19 to 58 years, with clinically manifested seasonal and perennial allergic rhinitis were studied. At the initiation and in the end of the three-year course of SCIT serum allergen-specific IgE and IgG4 were measured with ImmunoCAP system. The sIgE/sIgG4 ratio was calculated as a biomarker for immunologic effectiveness; (3) Results: There was a significant increase of sIgG4 antibodies (p < 0.05), while at the end of SCIT for the sIgE levels no significant changes were seen (p > 0.05). Moreover, 90% of patients showed a decrease of the IgE/IgG4 ratio; (4) Conclusions: In most of treated patients with AR, SCIT with Bulgarian allergen products leads to clear immunological changes. After a 3-year of SCIT there is a significant increase in allergen specific IgG4 levels and both decrease of sIgE and IgE/IgG4 ratio. sIgE, sIgG4 and IgE/IgG4 ratio can be used as a substantial biomarker for predicting immunological effectiveness of SCIT.