Persistent regulatory T‐cell response 2 years after 3 years of grass tablet <scp>SLIT</scp>: Links to reduced eosinophil counts, <scp>sIgE</scp> levels, and clinical benefit

Varona, Rosa; Ramos, Tania; Escribese, María M.; Jimeno, L; Galán, Agustín; Würtzen, Peter Adler; Vega, Francisco; Marín, Alicia; Martín, S; Carrera, Ana C.; Blanco, Carlos; Barber, Domingo

doi:10.1111/all.13553

Cited by 54 publications

(86 citation statements)

References 25 publications

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“…Effective immunotherapy has been shown to reverse the Th2 dominance with increased IFNγ production and reduction in Th2 cytokines, and to result in induction of Treg that produce TGF‐β and IL‐10, which are pivotal for the successful immune deviation in AIT . These changes in CD4 T‐cell cytokine production can be assessed through in vitro stimulation of PBMC from patients with allergen extracts.…”

Section: Candidate Biomarkers For Immune Monitoring In Allergen Immunmentioning

confidence: 99%

“…Furthermore, it has become evident that at least 3 years of treatment is needed to confer long-term clinical tolerance. 11,12 To overcome these limitations, several newer approaches are under investigation with altered administration or allergen preparation. 13 Intralymphatic immunotherapy (ILIT) is being trialled for aeroallergens with the aim to shorten the treatment period to 2 months using three ultrasound-guided injections of low-dose allergen applied with 1-month intervals.…”

Section: Allergen Immunotherapy: a Prototype Of Precision Medicinementioning

confidence: 99%

“…9 Other Ig isotypes are also found to increase, possibly contributing to the serum inhibitory activity on allergen-IgE binding. 11,21,40 Indeed, the reduction in IgE-facilitated allergen binding (IgE-FAB) following grass pollen SLIT was found to be associated with increased specific IgG1 and IgA as well as IgG4 in serum. 66 More recently, specific IgG2 serum levels were also found to be increased following SLIT for ryegrass pollen allergy with typically higher concentrations than IgG4.…”

Section: Immunoglobulinsmentioning

confidence: 99%

“…33,112 Flow cytometry of activation markers can be combined with intracellular staining for cytokines and intranuclear staining for the Treg transcription factor FoxP3. The latter approach allows for single-cell measurements and multi-parameter analysis, which have been applied to demonstrate reduction in Th2 cells following SLIT for HDM 34 and grass pollen, 11 as well as plasticity of Th2 cells developing a Treg phenotype following oral AIT for peanut allergy. 113 Furthermore, allergen-specific Tregs have been shown to expand following AIT for HDM and grass pollen allergies thereby increasing the ratio of allergen-specific Tregs over effector T cells.…”

Section: T Cellsmentioning

confidence: 99%

“…These approaches are deemed safe, but in a minority of patients, a strong reaction can already be observed at the (very low) starting dose, postponing or stopping further therapy. Furthermore, it has become evident that at least 3 years of treatment is needed to confer long‐term clinical tolerance . To overcome these limitations, several newer approaches are under investigation with altered administration or allergen preparation …”

Section: Introductionmentioning

confidence: 99%

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Recent developments and highlights in immune monitoring of allergen immunotherapy

Zelm

McKenzie

Varese

et al. 2019

Allergy

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Allergic diseases are the most common chronic immune-mediated disorders and can manifest with an enormous diversity in clinical severity and symptoms. Underlying mechanisms for the adverse immune response to allergens and its downregulation by treatment are still being revealed. As a result, there have been, and still are, major challenges in diagnosis, prediction of disease progression/evolution and treatment.Currently, the only corrective treatment available is allergen immunotherapy (AIT).AIT modifies the immune response through long-term repeated exposure to defined doses of allergen. However, as the treatment usually needs to be continued for several years to be effective, and can be accompanied by adverse reactions, many patients face difficulties completing their schedule. Long-term therapy also potentially incurs high costs. Therefore, there is a great need for objective markers to predict or to monitor individual patient's beneficial changes in immune response during therapy so that efficacy can be identified as early as possible. In this review, we specifically address recent technical developments that have generated new insights into allergic disease pathogenesis, and how these could potentially be translated into routine laboratory assays for disease monitoring during AIT that are relatively inexpensive, robust and scalable. K E Y W O R D Sallergen immunotherapy, allergy, biomarker, immune monitoring | 2343 ZELM Et aL.

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Section: Candidate Biomarkers For Immune Monitoring In Allergen Immunmentioning

confidence: 99%

Section: Allergen Immunotherapy: a Prototype Of Precision Medicinementioning

confidence: 99%

Section: Immunoglobulinsmentioning

confidence: 99%

Section: T Cellsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Recent developments and highlights in immune monitoring of allergen immunotherapy

Zelm

McKenzie

Varese

et al. 2019

Allergy

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Decreased numbers of metachromatic cells in nasal swabs in Japanese cedar pollinosis following sublingual immunotherapy

Otsuka

Matsune

et al. 2020

Immunity Inflam & Disease

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Background and Objective: Nasal symptoms were reduced following allergenspecific sublingual immunotherapy (SLIT) for allergic rhinitis. The mechanisms underlying the effectiveness of SLIT for Japanese cedar pollinosis are poorly understood. We studied changes in the numbers of metachromatic cells, eosinophils, and neutrophils following SLIT for Japanese cedar pollinosis. Methods: Nasal swabs were taken in the preseason (n = 32) and in pollinosis season (n = 49) from subjects given sublingual drop immunotherapy for an average duration of 1.5 years. The numbers of metachromatic cells (mast cells and basophils), eosinophils and neutrophils were determined and compared with those from untreated subjects in preseason (n = 65) and in season (n = 54). Results: SLIT subjects had a significantly reduced frequency of moderate to most severe symptoms in comparison to untreated subjects in preseason (P < .001, the Mann-Whitney U test), and (P < .00001) in season. Metachromatic cell counts in nasal swabs of SLIT subjects in preseason and in season were lower than those of untreated subjects (P = .014, the Mann-Whitney U test) and (P = .00001) respectively. Eosinophil numbers in SLIT subjects were not significantly different than in untreated subjects in both preseason (P = .29) and in season (P = .09). However, when SLIT subjects in season were divided into those with greater than or equal to 1.5 years, or <1.5 years of SLIT duration, the degree of eosinophilia in those with SLIT greater than or equal to 1.5 years was significantly lower (P = .011) than in untreated patients, but not in those with SLIT less than 1.5 years (P = .9). There were no significant differences in neutrophil numbers in nasal swabs between untreated and SLIT subjects in preseason and in season. Conclusion: One of mechanisms underlying the effectiveness of sublingual drop immunotherapy for Japanese cedar pollinosis is a reduction of the number

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Rational Design, Structure–Activity Relationship, and Immunogenicity of Hypoallergenic Pru p 3 Variants

Eichhorn

Hörschläger

Steiner

et al. 2019

Molecular Nutrition Food Res

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Scope Allergies to lipid transfer proteins involve severe adverse reactions; thus, effective and sustainable therapies are desired. Previous attempts disrupting disulfide bonds failed to maintain immunogenicity; thus, the aim is to design novel hypoallergenic Pru p 3 variants and evaluate the applicability for treatment of peach allergy. Methods and results Pru p 3 proline variant (PV) designed using in silico mutagenesis, cysteine variant (CV), and wild‐type Pru p 3 (WT) are purified from Escherichia coli. Variants display homogenous and stable protein conformations with an altered secondary structure in circular dichroism. PV shows enhanced long‐term storage capacities compared to CV similar to the highly stable WT. Using sera of 33 peach allergic patients, IgE‐binding activity is reduced by 97% (PV) and 71% (CV) compared to WT. Both molecules show strong hypoallergenicity in Pru p 3 ImmunoCAP cross‐inhibition and histamine release assays. Immunogenicity of PV is demonstrated with a phosphate‐based adjuvant formulation in a mouse model. Conclusions An in silico approach is used to generate a PV without targeting disulfide bonds, T cell epitopes, or previously reported IgE epitopes of Pru p 3. PV is strongly hypoallergenic while structurally stable and immunogenic, thus representing a promising candidate for peach allergen immunotherapy.

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Persistent regulatory T‐cell response 2 years after 3 years of grass tablet SLIT: Links to reduced eosinophil counts, sIgE levels, and clinical benefit

Abstract: Our results suggest that the immunological mechanisms underlying the sustained response after 2 years of cessation of immunotherapy (3-year treatment period) are linked to the acquisition and maintenance of a regulatory T-cell response.

Cited by 54 publications

References 25 publications

Recent developments and highlights in immune monitoring of allergen immunotherapy

Recent developments and highlights in immune monitoring of allergen immunotherapy

Decreased numbers of metachromatic cells in nasal swabs in Japanese cedar pollinosis following sublingual immunotherapy

Rational Design, Structure–Activity Relationship, and Immunogenicity of Hypoallergenic Pru p 3 Variants

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