Development of recombinant stable house dust mite allergen Der p 3 molecules for component‐resolved diagnosis and specific immunotherapy

Bouaziz, Ahlem; Walgraffe, David; Bouillot, Celine; Herman, Julie; Foguenne, Jacques; Gothot, André; Louis, Renaud; Hentges, François; Jacquet, Alain; Mailleux, Anne-Catherine; Chevigné, Andy; Galleni, Moreno; Adam, Emmanuelle; Dumez, Marie-Eve

doi:10.1111/cea.12452

Cited by 17 publications

(13 citation statements)

References 38 publications

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“…12 Recently similar low binding was reported for natural and functional rDer p 3 but a noncatalytic mutant showed higher binding for some sera providing a valuable reagent for further study. 13 The Der f 15 14 &18 15 allergens were discovered as important allergens of HDM-allergic dogs having primary structures similar to chitinase enzymes. It is however now known that the highly reactive and heavily glycosylated Der f 15 bound dog IgE via carbohydrate determinants 16 and that the IgE binding by humans found in 40% of allergic subjects is usually of low titre.…”

Section: Spectrum Of Hdm Allergensmentioning

confidence: 99%

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Hierarchy and molecular properties of house dust mite allergens

Thomas

2015

Allergology International

145

141

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The allergenic load of house dust mite allergy is largely constituted by a few proteins with a hierarchical pattern of allergenicity. The serodominant specificities are the group 1&2 and the group 23 faecal allergens. The collective IgE binding to the group 1&2 allergens can measure unequivocal HDM sensitisation better than HDM extracts although discrepancies have been found in regions with complex acarofauna suggesting a need to investigate the specificity with allergen components. The group 4, 5, 7&21 allergens that each induce responses in about 40% of subjects are mid-tier allergens accounting for most of the remaining IgE binding. Their titres are proportional to the concomitant responses to Der p1&2. Group 2 allergen variants have different antibody binding. Body proteins only occasionally induce sensitisation although a higher prevalence of binding by atopic dermatitis patients provides a new avenue of research. A broad spectrum of IgE binding has been associated with diverse symptoms but not with the severity of asthma which is associated with low IgG antibody. Some allergens such as the group 14 large lipid binding proteins and the recently described proteins Der f 24-33, need further investigation but with the cognoscence that other denominated allergens have been found to be minor sensitisers by comparative quantitative analyses. Scabies is a confounder for diagnosis with extracts, inducing cross-reactive antibodies with Der p 4&20 as is seafood allergy with cross reactivity to Der p 10 a minor HDM allergen. The HDM genome sequence can now be used to verify allelic and paralogous variations.

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Section: Spectrum Of Hdm Allergensmentioning

confidence: 99%

“…The natural group 7 allergens can be highly glycosylated (30%) and there are at least 3 different glycosylation isoforms found in varying degrees in different HDM extracts. 50 Minor allergens (groups 3,6,8,9,10,11,13,15,16,17,18,20) (Table 3) Group 3, 6 &9 allergens…”

Section: Group 7 Allergensmentioning

confidence: 99%

Hierarchy and molecular properties of house dust mite allergens

Thomas

2015

Allergology International

145

141

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“…Bouaziz et al. described a synthetic form of this allergen for use to improve the diagnosis of house dust mite allergy. Other cross‐reactive allergens can also impede the diagnostic value of a test, and one example was described in a research letter from Walton et al.…”

Section: Allergens and Their Interaction With The Immune Systemmentioning

confidence: 99%

“…Not all whole allergen preparations contain adequate amounts of all allergen components, and Der p 3 is one such component. Bouaziz et al [94] described a synthetic form of this allergen for use to improve the diagnosis of house dust mite allergy. Other cross-reactive allergens can also impede the diagnostic value of a test, and one example was described in a research letter from Walton et al [95].…”

Section: Allergens and Their Interaction With The Immune Systemmentioning

confidence: 99%

Developments in the field of allergy mechanisms in 2015 through the eyes of Clinical & Experimental Allergy

Roberts

Boyle

Bryce

et al. 2016

Clin Experimental Allergy

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“…Der p 1 has also been demonstrated to act as the activator of the precursors of Der p 3 and Der p 6 according to an uncommon activation cascade [ 5 , 6 , 7 ]. In contrast to Der p 1, little is known about the concentration of Der p 3 and Der p 6 in mite cultures and their IgE binding frequencies remain poorly characterized with IgE prevalence ranging from 10% to 50% for Der p 3 and around 40% for Der p 6 [ 8 , 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

Profiling the Extended Cleavage Specificity of the House Dust Mite Protease Allergens Der p 1, Der p 3 and Der p 6 for the Prediction of New Cell Surface Protein Substrates

Jacquet

Campisi

Szpakowska

et al. 2017

IJMS

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House dust mite (HDM) protease allergens, through cleavages of critical surface proteins, drastically influence the initiation of the Th2 type immune responses. However, few human protein substrates for HDM proteases have been identified so far, mainly by applying time-consuming target-specific individual studies. Therefore, the identification of substrate repertoires for HDM proteases would represent an unprecedented key step toward a better understanding of the mechanism of HDM allergic response. In this study, phage display screenings using totally or partially randomized nonameric peptide substrate libraries were performed to characterize the extended substrate specificities (P5–P4′) of the HDM proteases Der p 1, Der p 3 and Der p 6. The bioinformatics interface PoPS (Prediction of Protease Specificity) was then applied to define the proteolytic specificity profile of each protease and to predict new protein substrates within the human cell surface proteome, with a special focus on immune receptors. Specificity profiling showed that the nature of residues in P1 but also downstream the cleavage sites (P′ positions) are important for effective cleavages by all three HDM proteases. Strikingly, Der p 1 and Der p 3 display partially overlapping specificities. Analysis with PoPS interface predicted 50 new targets for the HDM proteases, including 21 cell surface receptors whose extracellular domains are potentially cleaved by Der p 1, Der p 3 and/or Der p 6. Twelve protein substrate candidates were confirmed by phage ELISA (enzyme linked immunosorbent assay). This extensive study of the natural protein substrate specificities of the HDM protease allergens unveils new cell surface target receptors for a better understanding on the role of these proteases in the HDM allergic response and paves the way for the design of specific protease inhibitors for future anti-allergic treatments.

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Development of recombinant stable house dust mite allergen Der p 3 molecules for component‐resolved diagnosis and specific immunotherapy

Abstract: rDer p 3-S196A should be used for the diagnosis of HDM allergy elicited by Der p 3, and proDer p 3 may represent a hypoallergen of Der p 3.

Cited by 17 publications

References 38 publications

Hierarchy and molecular properties of house dust mite allergens

Hierarchy and molecular properties of house dust mite allergens

Developments in the field of allergy mechanisms in 2015 through the eyes of Clinical & Experimental Allergy

Profiling the Extended Cleavage Specificity of the House Dust Mite Protease Allergens Der p 1, Der p 3 and Der p 6 for the Prediction of New Cell Surface Protein Substrates

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