Molecular variability of group 1 and 5 grass pollen allergens between Pooideae species: implications for immunotherapy

Chabre, Henri; Gouyon, Béatrice; Huet, A.; Boran-Bodo, V.; Nony, Emmanuel; Hrabina, M.; Fenaille, François; Lautrette, Aurélie; Bonvalet, Mélodie; Maillère, Bernard; Floch, Véronique Bordas-Le; Overtvelt, Laurence Van; Jain, K.; Ezan, Éric; Batard, Thierry; Moingeon, Philippe

doi:10.1111/j.1365-2222.2009.03380.x

Cited by 49 publications

(49 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In contrast, different IgE clones recognized group 1 allergens found in extracts of pollen of different species to varying degrees. The fact that all extracts but mays (Z. mays) were recognized by at least one recombinant group 1-specific IgE argues against extensive variability of such allergens, as reported by others (53,54), in the different extracts used to establish the assays. It is notable that even a small pool of IgE Abs, such as the one tested in this study, could have the potential to provoke allergic responses against such a wide range of different grass species.…”

Section: Discussionmentioning

confidence: 98%

Phl p 1–Specific Human Monoclonal IgE and Design of a Hypoallergenic Group 1 Grass Pollen Allergen Fragment

Levin

Rydnert

Källström

et al. 2013

The Journal of Immunology

View full text Add to dashboard Cite

Detailed understanding of how Abs of the IgE isotype interact with allergen at the onset of an allergic reaction is of great importance for deciphering mechanisms involved in the development of disease and may aid in the design of hypoallergenic variants. In this study, we have used a set of human monoclonal IgE Abs derived from the repertoires of allergic individuals, specific for the major timothy grass pollen allergen Phl p 1, to gain detailed information on the interaction between Abs and allergen. These allergen-specific IgE are to varying degrees cross-reactive toward both different allergen isoforms and various group 1 allergens originating from other grass species. The usage of human monoclonal IgE, as an alternative to polyclonal preparations or mouse Abs, allowed us to locate several important IgE-binding epitopes on the C-terminal domain of Phl p 1, all clustered to an IgE-binding “hot spot.” By introducing three mutations in the IgE-binding area of the C-terminal domain we were able to significantly reduce its reactivity with serum IgE. In conclusion, our study shows the great potential of using human monoclonal IgE as a tool for studies of the molecular interactions taking place during allergic responses. Furthermore, we present a novel IgE-hyporeactive fragment with the potential to be used as a safer hypoallergenic alternative in specific immunotherapy than the pollen extracts used today.

show abstract

Section: Discussionmentioning

confidence: 98%

Phl p 1–Specific Human Monoclonal IgE and Design of a Hypoallergenic Group 1 Grass Pollen Allergen Fragment

Levin

Rydnert

Källström

et al. 2013

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…A study with GRA also reported crossreactivity at the T-cell level [47], but this used an artificial system of two generated T-cell lines, and not T cells isolated from allergic patients (as in reference [46]); therefore, T cells specific for minimally cross-reactive epitopes may have been missed. A mixed grass-pollen extract is more likely to ensure that a broad and well-balanced panel of critical major and minor allergenic epitopes is present, whereas a single grass-pollen preparation would likely restrict the repertoire of allergenic epitopes to which a patient becomes desensitized [36,42]. Further clinical trials are needed to clarify whether differences in the degree of sensitization toward epitopes correlate with differences in the ability of SLIT to elicit immunotolerance.…”

Section: Excipients (Inactive Drug Additives)mentioning

confidence: 99%

“…The key difference between GRA and OA (apart from being 1-grass vs 5-grass-pollen preparations, respectively; see section 'Chemistry of the 5-grass-pollen tablet'), is that the former advocates perennial administration, unlike OA, which is only Chemistry of the 5-grass-pollen tablet In total, 13 groups of allergens that demonstrate significant IgE cross-reactivity have thus far been identified from pollen of the Pooideae subfamily of grasses [42]. Grass allergens belonging to groups 1 (glycoproteins) and 5 (non-glycosylated proteins) are well characterized and constitute the major allergens, which account for more than 80% of the allergenic potential of grasspollen [7,43].…”

Section: Excipients (Inactive Drug Additives)mentioning

confidence: 99%

“…A 5-grass-pollen extract better represents the natural exposure and sensitization conditions encountered by allergic patients, because the corresponding grass species are broadly distributed throughout North America and Europe, and polysensitization is common among patients [7,42]. Although high amino-acid sequence homology is found between Pooideae grass-pollens for group 1 and 5 allergens (90 and 55-80% homology, respectively), qualitative and quantitative differences exist in their expression between grass species [7,36,42]. Consequently, variations among allergic patients have been observed in the degree of sensitization toward both shared and species-specific epitopes from these allergens [7,36].…”

Section: Excipients (Inactive Drug Additives)mentioning

confidence: 99%

See 1 more Smart Citation

Five-grass-pollen sublingual immunotherapy tablet for the treatment of grass-pollen-induced allergic rhinoconjunctivitis: 5 years of experience

Didier

Wahn

Horak

et al. 2014

Expert Review of Clinical Immunology

View full text Add to dashboard Cite

OralairÒ (OA) (Stallergenes, Antony, France) is a unique pre-and co-seasonal 5-grass-pollen sublingual immunotherapy tablet launched in 2008, and now approved in 31 countries worldwide for the treatment of grass-pollen allergic rhinitis and rhinoconjunctivitis. OA is the first oral treatment with a consistent, well-balanced allergen extract that mimics natural exposure and sensitization. A wealth of data exists from over 5 years of clinical and realworld experience demonstrating the efficacy and safety of OA for grass-pollen-allergy treatment. OA is highly effective from the first pollen season in all patient subgroups, including children and those with comorbid mild asthma, irrespective of sensitization status and symptom severity. OA also has sustained long-term benefits for symptom control and quality of life. This article provides an overview of the pharmacodynamics and pharmacology of OA; its efficacy, safety, tolerability and cost-effectiveness for the treatment of allergic rhinitis and rhinoconjunctivitis and its role in clinical practice. Allergic rhinitis (AR) is a common chronic inflammatory illness, characterized by rhinorrhea, nasal congestion, sneezing, nasal and ocular pruritis and watery eyes [1]. Inhalation of allergens by sensitized individuals triggers the IgE-mediated release of inflammatory mediators and cytokines, leading to a rapid appearance of symptoms [2]. AR has historically been classified as 'seasonal' or 'perennial' depending on whether symptoms occur with seasonal exposure to aeroallergens or are present throughout the year. Seasonal AR is most commonly attributed to plant pollen and other outdoor allergens, while perennial AR is associated with indoor allergens, such as dust mites, mold, cockroaches and pet dander, although it can also be associated with pollen in areas where this is prevalent year-round [3,4].In 2001, the WHO-sponsored Allergic Rhinitis and its Impact on Asthma meeting produced guidelines proposing an alternative classification of the condition into 'intermittent' or 'persistent' AR, and grading symptoms as 'mild' or 'moderate/severe' [5]. Globally, the prevalence of seasonal ('hay fever') and perennial AR ranges from 7 to 42 and 1 to 13%, respectively, with the former being more common in children than adults [6]. The length of exposure to seasonal allergens is dependent on geographic location and climatic conditions [4]; in Europe, the main pollen season typically occurs from March to July, with slight variations according to latitude [7].Approximately 500 million people worldwide [6], including an estimated 30-60 million in the USA [4] 1309Drug Profile suffer from AR, and its prevalence is increasing in most countries [2]. It is estimated that from 10 to 30% of adults and up to 40% of the pediatric population have AR [3,9]. While AR does not directly lead to mortality, it places a considerable burden on affected individuals, who often have a reduced quality of life (QoL), compared with non-sufferers [10]. The physical symptoms of AR can cause sleep disturbance...

show abstract

“…Identification of the exact Pooideae member inducing primary sensitization may not be as important; both mixed grass pollen extracts and single representative species ( P. pratense pollen) have been argued to be effective [22,23,24,25]. …”

Section: Markers Of Genuine Sensitization To Major Pollen Sourcesmentioning

confidence: 99%

A Molecular Diagnostic Algorithm to Guide Pollen Immunotherapy in Southern Europe: Towards Component-Resolved Management of Allergic Diseases

Douladiris

Savvatianos

Roumpedaki

et al. 2013

Int Arch Allergy Immunol

View full text Add to dashboard Cite

Correct identification of the culprit allergen is an essential part of diagnosis and treatment in immunoglobulin E (IgE)-mediated allergic diseases. In recent years, molecular biology has made important advances facilitating such identification and overcoming some of the drawbacks of natural allergen extracts, which consist of mixtures of various proteins that may be allergenic or not, specific for the allergen source or widely distributed (panallergens). New technologies offer the opportunity for a more accurate component-resolved diagnosis, of benefit especially to polysensitized allergic patients. The basic elements of molecular diagnostics with potential relevance to immunotherapy prescription are reviewed here, with a focus on Southern European sensitization patterns to pollen allergens. We propose a basic algorithm regarding component-resolved diagnostic work-up for pollen allergen-specific immunotherapy candidates in Southern Europe; this and similar algorithms can form the basis of improved patient management, conceptually a ‘Component-Resolved Allergy Management'.

show abstract

Molecular variability of group 1 and 5 grass pollen allergens between Pooideae species: implications for immunotherapy

Cited by 49 publications

References 43 publications

Phl p 1–Specific Human Monoclonal IgE and Design of a Hypoallergenic Group 1 Grass Pollen Allergen Fragment

Phl p 1–Specific Human Monoclonal IgE and Design of a Hypoallergenic Group 1 Grass Pollen Allergen Fragment

Five-grass-pollen sublingual immunotherapy tablet for the treatment of grass-pollen-induced allergic rhinoconjunctivitis: 5 years of experience

A Molecular Diagnostic Algorithm to Guide Pollen Immunotherapy in Southern Europe: Towards Component-Resolved Management of Allergic Diseases

Contact Info

Product

Resources

About