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  1. Krishna SS, Farhana SA, T P A, Hussain SM, Viswanad V, Nasr MH, et al.
    Front Immunol, 2023;14:1229667.
    PMID: 37744376 DOI: 10.3389/fimmu.2023.1229667
    The increasing prevalence of food allergies worldwide and the subsequent life-threatening anaphylactic reactions often have sparse treatment options, providing only symptomatic relief. Great strides have been made in research and in clinics in recent years to offer novel therapies for the treatment of allergic disorders. However, current allergen immunotherapy has its own shortcomings in terms of long-term efficacy and safety, due to the local side effects and the possibility of anaphylaxis. Allergen-specific immunotherapy is an established therapy in treating allergic asthma, allergic rhinitis, and allergic conjunctivitis. It acts through the downregulation of T cell, and IgE-mediated reactions, as well as desensitization, a process of food tolerance without any allergic events. This would result in a protective reaction that lasts for approximately 3 years, even after the withdrawal of therapy. Furthermore, allergen-specific immunotherapy also exploits several routes such as oral, sublingual, and epicutaneous immunotherapy. As the safety and efficacy of allergen immunotherapy are still under research, the exploration of newer routes such as intra-lymphatic immunotherapy would address unfulfilled needs. In addition, the existence of nanoparticles can be exploited immensely in allergen immunotherapy, which would lead to safer and efficacious therapy. This manuscript highlights a novel drug delivery method for allergen-specific immunotherapy that involves the administration of specific allergens to the patients in gradual increasing doses, to induce desensitization and tolerance, as well as emphasizing different routes of administration, mechanism, and the application of nanoparticles in allergen-specific immunotherapy.
    Matched MeSH terms: Desensitization, Immunologic
  2. Reginald K, Nadeem K, Yap EZY, Latiff AHA
    Asian Pac J Allergy Immunol, 2024 Mar;42(1):1-13.
    PMID: 38165149 DOI: 10.12932/AP-030923-1687
    Fish allergy is one of the "big nine" categories of food allergens worldwide, and its prevalence is increasing with the higher demand for this nutritious food source. Fish allergies are a significant health concern as it is a leading cause of food anaphylaxis, accounting for 9% of all deaths from anaphylaxis. The gaps in treating fish allergies at present are the incomplete identification of fish allergens, lack of component-resolved diagnosis of fish allergens in the clinical setting, and the variability in sensitization profiles based on different fish consumption practices. Allergen immunotherapy (AIT) improves tolerance towards accidental consumption of fish and is longer lasting than pharmacotherapy. Current practice or research of fish AIT ranges from the use of whole fish via oral desensitization, to the use of purified recombinant parvalbumin and its hypoallergenic variant, passive IgG immunization, and modifying the allergenicity of parvalbumin by changing the diet of farmed fish. However, the focus of fish allergen-based studies in the context of AIT has been restricted to parvalbumins. More research is required to understand the involvement of other fish allergens, and several other strategies of AIT including peptide vaccines, DNA vaccines, hybrid allergens, and the use of nanobodies that have the capacity to treat multiple allergens have been proposed. For AIT, other important aspects to consider are the route of desensitization, and the biomarkers to assess the success of immunotherapy. Finally, we also address several clinical considerations for fish AIT.
    Matched MeSH terms: Desensitization, Immunologic
  3. Dhami S, Nurmatov U, Arasi S, Khan T, Asaria M, Zaman H, et al.
    Allergy, 2017 Nov;72(11):1597-1631.
    PMID: 28493631 DOI: 10.1111/all.13201
    BACKGROUND: The European Academy of Allergy and Clinical Immunology (EAACI) is in the process of developing Guidelines on Allergen Immunotherapy (AIT) for Allergic Rhinoconjunctivitis. To inform the development of clinical recommendations, we undertook a systematic review to assess the effectiveness, cost-effectiveness, and safety of AIT in the management of allergic rhinoconjunctivitis.

    METHODS: We searched nine international biomedical databases for published, in-progress, and unpublished evidence. Studies were independently screened by two reviewers against predefined eligibility criteria and critically appraised using established instruments. Our primary outcomes of interest were symptom, medication, and combined symptom and medication scores. Secondary outcomes of interest included cost-effectiveness and safety. Data were descriptively summarized and then quantitatively synthesized using random-effects meta-analyses.

    RESULTS: We identified 5960 studies of which 160 studies satisfied our eligibility criteria. There was a substantial body of evidence demonstrating significant reductions in standardized mean differences (SMD) of symptom (SMD -0.53, 95% CI -0.63, -0.42), medication (SMD -0.37, 95% CI -0.49, -0.26), and combined symptom and medication (SMD -0.49, 95% CI -0.69, -0.30) scores while on treatment that were robust to prespecified sensitivity analyses. There was in comparison a more modest body of evidence on effectiveness post-discontinuation of AIT, suggesting a benefit in relation to symptom scores.

    CONCLUSIONS: AIT is effective in improving symptom, medication, and combined symptom and medication scores in patients with allergic rhinoconjunctivitis while on treatment, and there is some evidence suggesting that these benefits are maintained in relation to symptom scores after discontinuation of therapy.

    Matched MeSH terms: Desensitization, Immunologic/methods*
  4. Sulaiman N, Othman AZ, Shahril NS, Abdul Rashid AM, Md Noh MSF
    SAGE Open Med Case Rep, 2017;5:2050313X17749080.
    PMID: 29318019 DOI: 10.1177/2050313X17749080
    Over the years, allopurinol has been widely used as the preferred choice of urate lowering therapy in patients with gout. However, its role in patients with renal impairment is limited; and adverse reactions are well documented. Febuxostat, a newer oral non-purine xanthine oxidase inhibitor has been proven in several trials to be more effective and tolerable compared to allopurinol and may be used in patients with renal impairment. Here, we describe a case of successful febuxostat desensitization in a patient with a history of allopurinol- and febuxostat-induced adverse cutaneous reaction, as well as the protocol utilized.
    Matched MeSH terms: Desensitization, Immunologic
  5. Seman WJW, Nasruddin AB, Noor NM
    J ASEAN Fed Endocr Soc, 2018;33(1):53-56.
    PMID: 33442111 DOI: 10.15605/jafes.033.01.09
    We present a case of a 27-year-old female with T2 DM who developed allergic reactions after commencement of insulin therapy. Trial with different types of insulin resulted in a series of allergic reactions ranging from urticarial rash to development of angioedema, bronchospasm and anaphylactic shock. She was successfully treated with a modified insulin desensitization protocol using rapid-acting insulin.
    Matched MeSH terms: Desensitization, Immunologic
  6. Joo Chan C, Richardo T, Lim RLH
    Int Rev Immunol, 2018;37(6):279-290.
    PMID: 30638084 DOI: 10.1080/08830185.2018.1509967
    Peanut allergy is a hypersensitivity reaction with symptoms varying from mild to severe anaphylaxis, tends to be lifelong and very few are able to outgrow this allergy. The prevalence of peanut allergy is highest among the Western countries and over the past decade, a 3.5 fold increase in prevalence of peanut allergy was reported among children in the United States. Increasing prevalence has also been observed among the Asian countries. As with other food allergies, peanut allergy reduces quality of life for the affected individuals and the social and economy burden of healthcare for peanut allergy is substantial. To date, there is no effective treatment for peanut allergy and disease management is by avoidance or relieve of symptoms via administration of epinephrine. Peanut allergy is a type-1 hypersensitivity reaction due to specific IgE production by activated T-helper type 2 (TH2) cells. Studies on various immunotherapy routes such as oral immunotherapy (OIT), sublingual immunotherapy and epicutaneous immunotherapy trials using peanut have shown the ability to induce desensitisation, shifting the allergen-specific cytokine production away from a TH2 respond. In the recent years, lactic acid bacteria probiotics have been reported to down-regulate allergy due to its inherent immunomodulatory properties. Wild-type probiotic in combination with peanut proteins or recombinant probiotics harbouring peanut allergens have been explored for OIT due to its ability to down-regulate allergen-specific-IgE production and the TH2 responses, while increasing the beneficiary population of TH1 regulatory T cells (Treg). This review discusses the current strategies in immunotherapy for peanut allergy.
    Matched MeSH terms: Desensitization, Immunologic/methods; Desensitization, Immunologic/trends*
  7. Gan CC, Jalalonmuhali M, Nordin NZ, Abdul Wahab MZ, Yahya R, Ng KP, et al.
    Transplant Proc, 2021 Apr;53(3):856-864.
    PMID: 33487455 DOI: 10.1016/j.transproceed.2020.10.038
    Malaysia has a low deceased-donor donation rate and has not embarked on a paired kidney exchange program; therefore, ABO-incompatible and HLA-incompatible transplantation remain the main contributor to the sustainability of the national kidney transplantation (KT) program. There were 26 cases of ABO-incompatible KTs performed from 2011 to 2018 in 3 major transplant centers, namely, Hospital Kuala Lumpur, University Malaya Medical Centre, and Prince Court Medical Centre. We collected perioperative and follow-up data through June 2019. The desensitization protocol varies and is center specific: the localized Japanese protocol and Swedish protocol with a target anti-A/B isoagglutinin titer of 16 or 32 on the day of transplant. The induction and tacrolimus-based maintenance protocol was nearly identical. The median follow-up time was 62.3 months (interquartile range, 37.0-79.7). Fifteen subjects had the highest predesensitization anti-A/B titer of ≥32 (57.7%). The acute cellular rejection and antibody-mediated rejection incidence were 12.5% (3 cases) and 8.3% (2 cases), respectively. Patient, graft, and death-censored graft survival rates were 96.2%, 92.3%, and 96.0%, respectively, 1 year post-living-donor KT (LDKT) and 96.2%, 87.2%, and 90.7%, respectively, 5 years post-LDKT. Our experience shows that ABO-incompatible LDKT using a suitable desensitization technique could be a safe and feasible choice for LDKT even with varied desensitization regimens for recipients with relatively high baseline isoagglutinin titers.
    Matched MeSH terms: Desensitization, Immunologic/methods; Desensitization, Immunologic/mortality*
  8. Salleh Hudin N, Teyssier A, Aerts J, Fairhurst GD, Strubbe D, White J, et al.
    Biol Open, 2018 Jun 15;7(6).
    PMID: 29632231 DOI: 10.1242/bio.031849
    While urbanization exposes individuals to novel challenges, urban areas may also constitute stable environments in which seasonal fluctuations are buffered. Baseline and stress-induced plasma corticosterone (cort) levels are often found to be similar in urban and rural populations. Here we aimed to disentangle two possible mechanisms underlying such pattern: (i) urban environments are no more stressful or urban birds have a better ability to habituate to stressors; or (ii) urban birds developed desensitized stress responses. We exposed wild-caught urban and rural house sparrows (Passer domesticus) to combined captivity and diet treatments (urban versus rural diet) and measured corticosterone levels both in natural tail feathers and in regrown homologous ones (cortf). Urban and rural house sparrows showed similar cortf levels in the wild and in response to novel stressors caused by the experiment, supporting the growing notion that urban environments are no more stressful during the non-breeding season than are rural ones. Still, juveniles and males originating from urban populations showed the highest cortf levels in regrown feathers. We did not find evidence that cortf was consistent within individuals across moults. Our study stresses the need for incorporating both intrinsic and environmental factors for the interpretation of variation in cortf between populations.
    Matched MeSH terms: Desensitization, Immunologic
  9. Kailaivasan TH, Timbrell VL, Solley G, Smith WB, McLean-Tooke A, van Nunen S, et al.
    PMID: 32025301 DOI: 10.1002/cti2.1103
    Objective: Globally, grass pollens (GP) are major aeroallergen triggers of allergic rhinitis (AR) and asthma. However, patterns of allergic sensitisation to pollen of temperate (Pooideae: Lolium perenne) and subtropical (Chloridoideae: Cynodon dactylon and Panicoideae: Paspalum notatum) subfamilies in diverse climates remain unclear. This study aims to evaluate the level of allergic sensitisation and IgE specificity for major GP allergens representing the three subfamilies in biogeographically distinct regions.

    Methods: Participants (GP-allergic with AR, 330; non-atopic, 29; other allergies, 54) were recruited in subtropical: Queensland, and temperate: New South Wales, Western and South Australia, regions. Clinical history, skin prick test (SPT), total and specific IgE to GP and purified allergens (ImmunoCAP) were evaluated. Cross-inhibition of sIgE with Pas n 1, Cyn d 1 and Lol p 1 by GP extracts was investigated.

    Results: Queensland participants showed higher sensitisation to P. notatum and C. dactylon than L. perenne GP. sIgE was higher to Pas n 1 and Cyn d 1, and sIgE to Pas n 1 and Cyn d 1 was inhibited more by Panicoideae and Chloridoideae, respectively, than Pooideae GP. Conversely, participants from temperate regions showed highest sensitisation levels to L. perenne GP and Lol p 1, and sIgE to Lol p 1 was inhibited more by Pooideae than other GP.

    Conclusion: Levels and patterns of sensitisation to subtropical and temperate GP in AR patients depended on biogeography. Knowledge of the specificity of sensitisation to local allergens is important for optimal diagnosis and choice of allergen-specific immunotherapy to maximise benefit.

    Matched MeSH terms: Desensitization, Immunologic
  10. Reginald K, Chew FT
    Mol Immunol, 2023 Sep;161:11-24.
    PMID: 37480600 DOI: 10.1016/j.molimm.2023.07.004
    PURPOSE OF REVIEW: This review evaluates the current modes of allergen-specific immunotherapy for cockroach allergens, in terms of clinical outcomes and explores future trends in the research and development needed for a more targeted cockroach immunotherapy approach with the best efficacy and minimum adverse effects.

    SUMMARY: Cockroach allergy is an important risk factor for allergic rhinitis in the tropics, that disproportionately affects children and young adults and those living in poor socio-economic environments. Immunotherapy would provide long-lasting improvement in quality of life, with reduced medication intake. However, the present treatment regime is long and has a risk of adverse effects. In addition, cockroach does not seem to have an immuno-dominant allergen, that has been traditionally used to treat allergies from other sources. Future trends of cockroach immunotherapy involve precision diagnosis, to correctly identify the offending allergen. Next, precision immunotherapy with standardized allergens, which have been processed in a way that maintains an immunological response without allergic reactions. This approach can be coupled with modern adjuvants and delivery systems that promote a Th1/Treg environment, thereby modulating the immune response away from the allergenic response.

    Matched MeSH terms: Desensitization, Immunologic
  11. Zepeda-Ortega B, Goh A, Xepapadaki P, Sprikkelman A, Nicolaou N, Hernandez REH, et al.
    Front Immunol, 2021;12:608372.
    PMID: 34177882 DOI: 10.3389/fimmu.2021.608372
    The prevalence of food allergy has increased over the last 20-30 years, including cow milk allergy (CMA) which is one of the most common causes of infant food allergy. International allergy experts met in 2019 to discuss broad topics in allergy prevention and management of CMA including current challenges and future opportunities. The highlights of the meeting combined with recently published developments are presented here. Primary prevention of CMA should start from pre-pregnancy with a focus on a healthy lifestyle and food diversity to ensure adequate transfer of inhibitory IgG- allergen immune complexes across the placenta especially in mothers with a history of allergic diseases and planned c-section delivery. For non-breastfed infants, there is controversy about the preventive role of partially hydrolyzed formulae (pHF) despite some evidence of health economic benefits among those with a family history of allergy. Clinical management of CMA consists of secondary prevention with a focus on the development of early oral tolerance. The use of extensive Hydrolysate Formulae (eHF) is the nutrition of choice for the majority of non-breastfed infants with CMA; potentially with pre-, probiotics and LCPUFA to support early oral tolerance induction. Future opportunities are, among others, pre- and probiotics supplementation for mothers and high-risk infants for the primary prevention of CMA. A controlled prospective study implementing a step-down milk formulae ladder with various degrees of hydrolysate is proposed for food challenges and early development of oral tolerance. This provides a more precise gradation of milk protein exposure than those currently recommended.
    Matched MeSH terms: Desensitization, Immunologic/methods*
  12. Ferguson GC, Nunn AJ, Fox W, Miller AB, Robinson DK, Tall R
    Tubercle, 1971 Sep;52(3):166-81.
    PMID: 4106401
    Matched MeSH terms: Desensitization, Immunologic
  13. Chan SL, Ong TC, Gao YF, Tiong YS, Wang de Y, Chew FT, et al.
    J Immunol, 2008 Aug 15;181(4):2586-96.
    PMID: 18684949
    A high incidence of sensitization to Blomia tropicalis, the predominant house dust mite species in tropical regions, is strongly associated with allergic diseases in Singapore, Malaysia, and Brazil. IgE binding to the group 5 allergen, Blo t 5, is found to be the most prevalent among all B. tropicalis allergens. The NMR structure of Blo t 5 determined represents a novel helical bundle structure consisting of three antiparallel alpha-helices. Based on the structure and sequence alignment with other known group 5 dust mite allergens, surface-exposed charged residues have been identified for site-directed mutagenesis and IgE binding assays. Four charged residues, Glu76, Asp81, Glu86, and Glu91 at around the turn region connecting helices alpha2 and alpha3 have been identified to be involved in the IgE binding. Using overlapping peptides, we have confirmed that these charged residues are located on a major putative linear IgE epitope of Blo t 5 from residues 76-91 comprising the sequence ELKRTDLNILERFNYE. Triple and quadruple mutants have been generated and found to exhibit significantly lower IgE binding and reduced responses in skin prick tests. The mutants induced similar PBMC proliferation as the wild-type protein but with reduced Th2:Th1 cytokines ratio. Mass screening on a quadruple mutant showed a 40% reduction in IgE binding in 35 of 42 sera of atopic individuals. Findings in this study further stressed the importance of surface-charged residues on IgE binding and have implications in the cross-reactivity and use of Blo t 5 mutants as a hypoallergen for immunotherapy.
    Matched MeSH terms: Desensitization, Immunologic
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