HLA-DPB1 alleles in house dust mite allergic patients.

Associations were sought between the presence of allergic sensitivity to Der p 1, a major allergen from the house dust mite, and the HLA-DPB1 genotype. Whilst allergic patients did not differ from controls in DPB1 allelic distribution, there was a correlation of DPB1*11011 with strongly reactive T-cell proliferative responses to Der p 1 and high titre specific IgE to Dermatophagoides pteronyssinus.     

HLA DPB1*0201 allele is negatively associated with immunoglobulin E responsiveness specific for house dust mite allergens in Taiwan

BACKGROUND: House dust mite (HDM) Dermatophagoides pteronyssinus is the most important source of indoor allergens that cause allergic diseases in Taiwan. We prepared purified HDM allergens (Der p 1, Der p 2 and Der p 5) to detect allergen-specific immunoglobulin (Ig) E responsiveness among a large number of test subjects. The robust genetic typing system for HLA class II genes also facilitated the study on association of HLA and allergic response toward HDM. OBJECTIVE: This study intended to investigate the association between HLA class II alleles and the IgE responsiveness to the major allergens from HDM, D. pteronyssinus. METHODS: Two hundred and forty-eight subjects were selected for HLA association study. Plasma HDM allergen (Der p 1, Der p 2, Der p 5) -specific IgE and Der p 2-specific IgG antibodies were detected by ELISA, while HLA class II -DRB1, -DQA1, -DQB1, -DPB1 genetic polymorphism was determined by polymerase chain reaction/sequence-specific oligonucleotide probe hybridization (PCR/SSOPH). Statistical comparison of the allelic distribution of each HLA class II genes among the individuals with/without HDM allergen-specific IgE and IgG antibodies were performed. RESULTS: There was no significant association between HLA DRB1, DQB1, DQA1 alleles and HDM-specific IgE responsiveness noted. Only DRB1*0803 and the linked DQA1*0103 alleles showed positive association with Der p 5-specific IgE responsiveness. However, we found that HLA-DPB1*1301 predisposed subjects to IgE responsiveness to HDM Der p 5. HLA DPB1*0501 was weakly associated with the IgE responsiveness to HDM Der p 1 and Der p 5. There was a strong negative association between the HLA-DPB1*0201 allele with IgE responsiveness to Der p 1 (OR: 0.30, P 相似文献   

Molecular characterization of Der p 10: a diagnostic marker for broad sensitization in house dust mite allergy

Background Tropomyosins represent clinically relevant seafood allergens but the role of mite tropomyosin, Der p 10, in house dust mite (HDM) allergy has not been studied in detail. Objective To express and purify a recombinant Der p 10 with equivalent IgE reactivity as natural Der p 10 and to evaluate its IgE reactivity and allergenic activity in HDM‐allergic patients. Methods rDer p 10 was expressed in Escherichia coli, purified and characterized by mass spectrometry and circular dichroism. It was tested for IgE reactivity in 1322 HDM‐allergic patients. Detailed IgE‐reactivity profiles to six HDM allergens (Der p 1, 2, 5, 7, 10, 21) were established for subgroups of Der p 10‐positive and ‐negative patients. The allergenic activity of rDer p 10 was evaluated in basophil degranulation experiments. Results rDer p 10 is an α‐helical protein sharing IgE epitopes with nDer p 10. It is recognized by 15.2% of HDM‐allergic patients. Der p 10‐negative patients were primarily sensitized to Der p 1 and/or Der p 2, whereas Der p 10‐positive patients reacted to several other HDM allergens besides the major allergens (Der p 1, Der p 2) or showed a rather selective Der p 10 reactivity. The allergenic activity of Der p 10 was generally low but patients could be identified who suffered from clinically relevant HDM allergy due to Der p 10 sensitization. Conclusion and Clinical Relevance Der p 10 may be a diagnostic marker for HDM‐allergic patients with additional sensitization to allergens other than Der p 1 and Der p 2. Such patients may require attention when allergen‐specific immunotherapy is considered. Cite this as: Y. Resch, M. Weghofer, S. Seiberler, F. Horak, S. Scheiblhofer, B. Linhart, I. Swoboda, W. R. Thomas, J. Thalhamer, R. Valenta and S. Vrtala, Clinical & Experimental Allergy, 2011 (41) 1468–1477.     

Molecular mimicry as the key to the dominance of the house dust mite allergen Der p 2

Evaluation of: Trompette A, Divanovic S, Visintin A et al. Allergenicity resulting from functional mimicry of a Toll-like receptor complex protein. Nature 457, 585–588 (2009).

The majority of complex sources of allergen contain a small number of dominant allergens that bind at least half of the IgE antibodies of allergic subjects. For the house dust mite Dermatophagoides pteronyssinus, these allergens are Der p 1 and Der p 2. There is evidence that the cysteine-protease activity of Der p 1 imparts adjuvant activity to the allergen. It has now been shown that Der p 2 mimics the activity of its fellow ML-domain protein, MD-2, by presenting lipopolysaccharide to Toll-like receptor-4 for the activation of inflammatory genes. In accord with this, Der p 2 presented with lipopolysaccharide also induced enhanced type 1 allergic sensitization of mice, even when they were deficient in MD-2. The mimicry of MD-2 can thus also self adjuvant Der p 2 to enhance it allergenicity. This not only describes an intriguing mechanism for enhancing allergenicity but also, since both of the dominant mite allergens have intrinsic adjuvant activity, exemplifies an important principle for driving allergic sensitization.     

Histamine induces Th2 activation through the histamine receptor 1 in house dust mite rhinitic but not asthmatic patients

Background Effects of mast cell‐released histamine on smooth muscle and endothelial cells are considered as responsible of immediate symptoms of anaphylaxis. However, little is known about histamine effects on Th2 lymphocytes, which orchestrate the allergic reaction upstream of mast cells. Objective We addressed this question in house dust mite (HDM) allergics, according to the presence of rhinitis or asthma and allergen stimulation. Methods Peripheral blood mononuclear cell from 15 rhinitic and 14 asthmatic HDM‐allergic subjects and 16 controls were cultured with Der p 1 or histamine. The effect of Der p 1 on histamine receptor (H1R and H2R) expression was studied. T‐cell cytokine production was studied upon Der p 1 or histamine stimulation. The role of H1R in histamine effects was assessed with levocetirizine. Results H1R and H2R are overexpressed on T cells from asthmatic but not from rhinitic subjects. Der p 1 increases H1R expression on CD4⁺ cells from both allergic groups, and decreases it in controls, on CD4⁺ and CD8⁺ subsets. Der p 1 decreases T‐cell H2R expression in asthmatics. Allergen increases IL‐4 and IL‐13 in both allergic groups. Histamine increases Th2 cytokines in rhinitics only, and levocetirizine abolishes this effect. In asthmatics and controls, histamine decreases T‐cell cytokines through a non‐H1R dependent pathway. Conclusion In rhinitis but not in asthma, histamine is able to increase allergic inflammation by increasing Th2 cytokine production in a positive feedback dependent on H1R. This result could explain in part why H1R antagonists, are very efficient in rhinitis, but not in asthma. Cite this as: K. Botturi, Y. Lacoeuille, D. Vervloet and A. Magnan, Clinical & Experimental Allergy, 2010 (40) 755–762.     

Characterization of Der p 21, a new important allergen derived from the gut of house dust mites

Background: The house dust mite (HDM) Dermatophagoides pteronyssinus is a major allergen source eliciting allergic asthma. The aim of the study was to identify new important HDM allergens associated with allergic asthma. Methods: A cDNA coding for a new mite allergen, designated Der p 21, was isolated using immunoglobulin E (IgE) antibodies from patients with allergic asthma out of a D. pteronyssinus expression cDNA library and expressed in Escherichia coli. Results: Circular dichroism analysis of the purified allergen showed that rDer p 21 (14 726 Da) is one of the few mite allergens with an α‐helical secondary structure. The protein exhibited high thermal stability and refolding capacity, and, as determined by small angle X‐ray scattering, formed a dimer consisting of two flat triangles. rDer p 21 bound high levels of patients’ IgE antibodies and showed high allergenic activity in basophil activation experiments. Rabbit anti‐Der p 21 IgG antibodies inhibited mite‐allergic patients’ IgE binding and allowed the ultrastructural localization of the allergen in the midgut (epithelium, lumen and faeces) of D. pteronyssinus by immunogold electron microscopy. Der p 21 revealed sequence homology with group 5 mite allergens, but IgE and IgG reactivity data and cross‐inhibition studies identified it as a new mite allergen. Conclusions: Der p 21 is a new important mite allergen which is liberated into the environment via faecal particles and hence may be associated with allergic asthma.     

Epitope mapping and structural analysis of the anti-Der p 1 monoclonal antibody: insight into therapeutic potential

Group 1 allergen from Dermatophagoid pteronyssinus (Der p 1) belongs to the papain-like cysteine protease family and is a major cause of allergic rhinitis and asthma. An anti-Der p 1 monoclonal antibody, mAb W108, was selected and isolated from Der p-specific IgG2b-producing hybridoma clones. Two-dimensional electrophoresis and immunoblotting showed that mAb W108 reacted with four components of Der p extracts with a molecular mass of 35 kDa and pI values varying from 4 to 6; it also reacted with IgE antibodies in the sera of Der p-sensitive patients. In the competitive assay and using azocasein as a substrate, we found that mAb W108 inhibited not only the binding of Der p 1, but also its cysteine protease activity in a dose-dependent manner. The two peptide segments of Der p 1 identified by mAb W108 (aa 151–197 and 286–320) were parts of inter-connecting loops located in the substrate-binding cleft and on the surface of the domain comprising mainly β-sheets. From the predicted interaction between the amino acid sequence in the CDR3 of mAb W108 and Der p 1-binding epitopes, the possible binding sites for mAb W108 to Der p 1 may sterically hinder the IgE epitope and the active site of cysteine protease activity. Administration of mAb W108 in the Der p-sensitized murine model of asthma alleviated allergen-induced airway inflammation and the Th2 cytokine immune response, suggesting its therapeutic potential. These findings can provide new insights into understanding IgE-mediated disease and the design of modified allergen vaccines for future allergen-specific immunotherapy.     

Der p 1-pulsed myeloid and plasmacytoid dendritic cells from house dust mite-sensitized allergic patients dysregulate the T cell response

Although reports suggest that dendritic cells (DC) are involved in the allergic reaction characterized by a T helper cell type 2 (Th2) profile, the role of myeloid (M-DC) and plasmacytoid DC (P-DC), controlling the balance Th1/Th2, remains unknown. Here, we showed that in Dermatophagoides pteronyssinus (Dpt)-sensitized allergic patients and in healthy donors, M-DC displayed a higher capacity to capture Der p 1, a major allergen of Dpt, than did P-DC. However, Der p 1-pulsed M-DC from healthy subjects overexpressed CD80 and secreted interleukin (IL)-10, whereas M-DC from allergic patients did not. In contrast, with Der p 1-pulsed P-DC from both groups, no increase in human leukocyte antigen-DR, CD80, and CD86 and no IL-10 secretion were detected. When cocultured with allogeneic naive CD4(+) T cells from healthy donors, Der p 1-pulsed M-DC from allergic patients favored a Th1 profile [interferon (IFN)-gamma(high)/IL-4(low)] and Der p 1-pulsed P-DC, a Th2 profile (IFN-gamma(low)/IL-4(high)). In healthy donors, no T cell polarization (IFN-gamma(low)/IL-4(low)) was induced by Der p 1-pulsed M-DC or P-DC, but in response to Der p 1-pulsed M-DC, T cells secreted IL-10. The neutralization of IL-10 produced by Der p 1-pulsed M-DC from healthy donors led to an inhibition of IL-10 production by T cells and a polarization toward a type 1. Thus, IL-10 produced by M-DC might be an essential mediator controlling the balance between tolerance and allergic status. In addition, P-DC could contribute to the steady state in healthy donors or to the development of a Th2 response in allergic donors.     

The protease allergen Der p 1 cleaves cell surface DC-SIGN and DC-SIGNR: experimental analysis of in silico substrate identification and implications in allergic responses

Background The cysteine protease Der p 1 from the house dust mite Dermatophagoides pteronyssinus is one of the most potent allergens known. An attractive mechanism for a component of Der p 1 allergenicity lies in its ability to cleave key regulatory molecules from leucocyte surfaces, subverting cellular function and driving abnormal immunoglobulin E (IgE) responses. Objective Although CD23, CD25 and CD40 have already been identified as major Der p 1 targets, other significant substrates may also exist. Methods To investigate this, knowledge of the proteolytic properties of Der p 1 was used to perform in silico digestion of human dendritic cell surface proteins, using the prediction of protease specificity (PoPS) bioinformatics tool, in conjunction with cellular in vitro analysis and cleavage site determination. Results Targets identified included DC‐SIGN and DC‐SIGNR, two C‐type lectins implicated mostly in pathogen trafficking. Treatment of positively expressing cells with Der p 1 led to loss of detectable surface DC‐SIGN and DC‐SIGNR. Digestion of purified soluble recombinant DC‐SIGN and DC‐SIGNR, followed by N‐terminal sequencing and MALDI mass spectrometry, indicated in each case one major cleavage site and several minor sites, the former correlating well with Der p 1 enzymology and the folded state of the substrate proteins. Loss of DC‐SIGN from the cell surface led to reduced binding of intracellular adhesion molecule‐3, an endogenous DC‐SIGN ligand expressed on naïve T cells which is thought to be involved in T‐helper type 1 cytokine signalling. Conclusion These data provide evidence of lectin involvement in the initiation of the allergic response and the value of using genome‐wide in silico digestion tools.     

Involvement of the mannose receptor in the uptake of Der p 1, a major mite allergen,by human dendritic cells

BACKGROUND: Immature dendritic cells (DCs) take up antigens in peripheral tissues and, after antigen processing, mature to efficiently stimulate T cells in secondary lymph nodes. In allergic airway diseases DCs have been shown to be involved in the induction and maintenance of a T(H)2-type profile. OBJECTIVE: The present study was undertaken to determine pathways of Der p 1 (a house dust mite allergen) uptake by human DCs and to compare Der p 1 uptake between DCs from patients with house dust mite allergy and DCs from healthy donors. METHODS: Monocyte-derived DCs (MD-DCs) were obtained from patients with house dust mite allergy (n = 13) and healthy donors (n = 11). Der p 1 was labeled with rhodamine. Der p 1 uptake by MD-DCs was analyzed by means of flow cytometry and confocal microscopy. RESULTS: Rhodamine- labeled Der p 1 was demonstrated to be taken up by MD-DCs in a dose-, time-, and temperature- dependent manner. The involvement of the mannose receptor (MR) in the Der p 1 uptake was demonstrated by using (1) inhibitors of the MR- mediated endocytosis (mannan and blocking anti-MR mAb), which inhibited the Der p 1 uptake from 40 % to 50 %, and (2) confocal microscopy showing the colocalization of rhodamine-labeled Der p 1 with FITC-dextran. Interestingly, compared with DCs from healthy donors, DCs from allergic patients expressed more MR and were more efficient in Der p 1 uptake. CONCLUSION: These results suggest that the MR could play a key role in the Der p 1 allergen uptake by DCs and in the pathogenesis of allergic diseases in dust mite -sensitive patients.     

Direct regulatory immune activity of lactic acid bacteria on Der p 1-pulsed dendritic cells from allergic patients

BACKGROUND: Lactic acid bacteria (LAB) are suggested to play a regulatory role in the development of allergic reactions. However, their potential effects on dendritic cells (DCs) directing the immune polarization remain unclear. OBJECTIVE: The immunologic effect of Lactobacillus plantarum NCIMB 8826 (LAB1) on monocyte-derived dendritic cells (MD-DCs) from patients allergic to house dust mite was evaluated. METHODS: MD-DCs were stimulated for 24 hours with the related allergen Der p 1 in the presence or absence of LAB1. Cell-surface markers were assessed by means of FACS analysis, and the key polarizing cytokines IL-12 and IL-10 were quantified. The subsequent regulatory effect of pulsed MD-DCs on naive or memory T cells was evaluated by determining the T-cell cytokine profile. RESULTS: LAB1 induced the maturation of MD-DCs, even if pulsed with Der p 1. Interestingly, after incubation with LAB1 and Der p 1, MD-DCs produced higher amounts of IL-12 than Der p 1-pulsed DCs. Indeed, the T H 2 cytokine (IL-4 and IL-5) production observed when naive or memory autologous T cells were cocultured with Der p 1-pulsed MD-DCs was highly reduced in the presence of LAB1. Finally, in contrast to naive or memory T cells exposed once to Der p 1-pulsed DCs, T cells stimulated by MD-DCs pulsed with Der p 1 and LAB1 failed to produce T H 2 cytokines in response to a new stimulation with Der p 1-pulsed DCs. CONCLUSION: Thus in the presence of LAB1, MD-DCs from allergic patients tend to reorientate the T-cell response toward a beneficial T H 1 profile.     

Lack of evidence of a significant association between HLA-DR, DQ and DP genotypes and atopy in families with HDM allergy

Background HLA class II genetic polymorphism has been variably implicated in susceptibility to specific immune responsiveness to house dust mite (HDM) allergens, and may also influence the development of atopy. Objective In order to assess accurately the influence of HLA alleles in the atopic immune response, we typed 22 families selected from 131 previously obtained randomly selected families (i.e. without regard to atopy or asthma), chosen on the basis of two or more members having skin prick reactivity to HDM. Methods Each individual was fully typed for HLA-DRB1, DQA1, DQB1 and DPB1 class II alleles using a combination of sequence-specific oligonucleotide probes (SSOP) and sequence-specific primer (SSP) polymerase chain reaction (PCR) typing and direct sequencing. Results Using appropriate statistical tests, no significant allelic associations were found between any DRBl, DQB1 or DPBl alleles and atopy or skin prick reactivity to Dermataphagoides pteronyssinus (Der p) or D. farinae (Der f). However, positive associations were found between DQA 1*0301 and skin prick reactivity to Der f (P= 0.009) and atopy (P= 0.027). Sib-pair analysis revealed no significant sharing of alleles between affected sib pairs for any of the phenotypes studied. Conclusion These results fail to confirm a previously reported association between the DRB1*04 and 07 haplotypes and atopy, and suggest that HLA class II restriction does not play a major role in the development of the IgE response to domestic house dust mite allergens in the British population.     

Diagnostic significance of in vitro T-cell proliferative responses to house-dust mite Der p 1 in children with dust-mite allerev

The study aimed to investigate the possible diagnostic significance of T-cell proliferative responses to purified Der p 1 antigen in allergic children with and without allergic sensitization to house-dust-mite (HDM) allergens. T-cell reactivity to purified Der p 1antigen was analyzed in 24 children with allergic sensitization to HDM demonstrated by RAST and/or positive skin prick tests. Twelve healthy young adults and 11 children with allergic sensitizations other than HDM served as controls. Of 25 HDM-allergic patients, 16 displayed strong T-cell reactivity to Der p 1 (stimulation indices >3): nine patients showed no T-cell proliferation despite the presence of specific IgE, and five showed no responses despite positive skin prick test. In two patients, a weak T-cell response to Der p 1 could be demonstrated in the absence of specific IgE and negative skin test result. The two affected subjects did not show evidence of mite allergy. No T-cell responses were observed in adult controls (stimulation indices<3). We conclude that the assessment of T-cell reactivity to Der p 1 is of little value for the diagnosis of HDM allergy. The importance of T-cell proliferative responses for the study of the pathogenesis of HDM allergy remains unchallenged.     

IgE and monoclonal antibody binding by the mite allergen Der p 7

Background The recently characterized group 7 house dust mite allergens give positive skin-test reactions in 53% of allergie patients. Objective This study was performed to compare the IgE bindinig activity of natural and recombinant Der p 7, to measure the binding in allergic sera in comparison to major allergen Der p 2 and characterize the response by competitive inhibition with monoclonal antibodies. Methods IgE anti Der p 2 and Der p 7 antibodies against the recombinant allergens and monoclonal binding activities were measured by a solid phase radioimmune assay. Reslts A competitive binding assay showed that rDer p 7 inhibited 91% of IgE-binding to natural Der p 7 in 2 sera and 73% in a further two. The IgE binding of rDer p 2 and Der p 7 from 41 sera was then compared. Of the sera 88% and 46% respectively showed positive binding. All of the 19 sera which bound Der p 7 also bound Der p 2 but 11 (58%) had bound IgE to Der p 7 as high or higher than the binding to Der p 2. These sera were mostly high responders to both allergens. A panel of six monoclonal antibodies produced against either rDer p 7 or rDer f 7 was used for epitope analysis. All of these reaeted with eaeh allergen by enzyme linked immunosorbent assay (ELISA) and immunoblotting. Two patterns of cross inhibition of monoclonal antibody binding were observed and of five monoclonal antibodies tested, lour could inhibit the binding of IgE (WH9, WH22. WPS and HD19) while one (WH14) could not. Conclusions Although Der p 7 only reacts with 50% of allergic sera it often has a high IgE binding activity and may be more important than the major Der p 2 allergen in a high percentage of subjects. The combined competitive inhibition experiments show the IgE response is directed at several specilieities.     

Der p 2 can induce bystander activation of B cells derived from patients with systemic lupus erythematosus

Although many patients with SLE also have allergies, the immunological events triggering the onset and progression of the clinical manifestations of SLE by allergens have yet to be clarified. A total of three autoantigens, phosphoglycerate kinase 1 (PGK-1), triosephosphate isomerase (TIM) and enolase were identified by autologous serum in B cell lysate derived from HDM allergic SLE patients after Der p 2 stimulation. Autoantigen, TRIM-21 expression were also significantly increased in B cells derived from HDM allergic SLE patients. In PBMCs derived from SLE patients, the concentration of anti-PGK-1 was significantly upregulated after Der p 2 stimulation compared to HDM allergic without SLE patients and healthy subjects. Inflammatory related cytokines and chemokines include IL-1β, IL-6, IL-8, CXCL5 could be upregulated after Der p 2 stimulation in PBMCs derived from HDM allergic SLE patients. In conclusion, our data demonstrated that long-term allergen exposure could be a contributing factor in the development of SLE.     

The structure of the mite allergen Blo t 1 explains the limited antibody cross‐reactivity to Der p 1

The Blomia tropicalis (Blo t) mite species is considered a storage mite in temperate climate zones and an important source of indoor allergens causing allergic asthma and rhinitis in tropical and subtropical regions. Here, we report the crystal structure of one of the allergens from Blo t, recombinant proBlo t 1 (rproBlo t 1), determined at 2.1 Å resolution. Overall, the fold of rproBlo t 1 is characteristic for the pro‐form of cysteine proteases from the C1A class. Structural comparison of experimentally mapped Der f 1/Der p1 IgG epitopes to the same surface patch on Blo t 1, as well as of sequence identity of surface‐exposed residues, suggests limited cross‐reactivity between these allergens and Blo t 1. This is in agreement with ELISA inhibition results showing that, although cross‐reactive human IgE epitopes exist, there are unique IgE epitopes for both Blo t 1 and Der p 1.     

Association of Single Nucleotide Polymorphisms in the MD-2 Gene Promoter Region With Der p 2 Allergy

Purpose

Sensitization to house dust mite (Dermatophagoides pteronyssinus) is a considerable risk factor for the progression of allergic disease. The group 2 allergen from Dermatophagoides pteronyssinus, Der p 2, is considered a major one in patients with specific immunoglobulin E (IgE) to Der p 2. Der p 2 has structural homology with myeloid differentiation 2 (MD-2), which is involved in the lipopolysaccharide-binding component of the Toll-like receptor 4 signaling pathway and the development of inflammation. The aim of this study was to examine the genetic association of single nucleotide polymorphisms (SNPs) in the promoter region of MD-2 with Der p 2-sensitive allergy.

Methods

We investigated associations between cohort''s characteristics, including 280 allergic and 80 healthy subjects by examining total IgE, eosinophils, D. pteronyssinus-specific IgE, Der p 2-specific IgE, the number of IgE-producing B cells induced by Der p 2, and the odds ratio of allergic symptoms.

Results

Based on the 1,000 genome project data, the minor allele frequencies of the rs1809441 and rs1809442 are 0.467 and 0.474, respectively. However, the correlation of linkage disequilibrium (LD) between these 2 SNPs is D''=1, the genotype frequencies of the 2 MD-2 (LY96) SNPs (rs1809441 and rs1809442) that are located nearby were significantly different between allergic and health subjects: the TT genotype of rs1809441 and the GG genotype of rs1809442 were more frequent in allergic subjects than in healthy subjects (16.1% vs 2.5% in both genotypes). The allergic patients with these genotypes exhibited significantly higher levels of D. pteronyssinus-specific IgE and Der p 2-specific Ig E, and a larger number of Der p 2-activated B cells. In addition, these 2 SNPs in the MD-2 promoter region were significantly associated with the prevalence of nasal, skin, and asthmatic allergic symptoms.

Conclusions

Our results indicated that 2 SNPs in the MD-2 promoter region were significantly associated with Der p 2-specific Ig E, and thereby suggest that these SNPs may play a major role in susceptibility to Der p 2-triggered immune responses in a Taiwanese population.     

Probiotic Escherichia coli Nissle 1917 activates DC and prevents house dust mite allergy through a TLR4‐dependent pathway

Experimental animal and human studies have demonstrated that probiotic strains have beneficial effects on allergy. Here we report that the probiotic Escherichia coli Nissle 1917 strain (EcN) is able to activate DC, as shown by important cytokine synthesis together with up‐regulation of membrane expression of CD40, CD80 and CD86. This EcN‐induced DC activation was strictly dependent on the TLR4 signaling pathway and was also associated with stimulation of NF‐κB and MAPK. We next investigated the prophylactic potential of i.n. co‐administration of EcN with a recombinant form of Der p 1 (ProDer p 1) in a murine model of mite allergy. I.n. vaccinations with EcN plus ProDer p 1 prevented the subsequent allergic response following Der p 1 sensitization and airway challenge with aerosolized mite extracts through the induction of an allergen‐specific IgG2a response, the prevention of specific IgE production and a strong reduction of IL‐5 secretion by allergen‐restimulated splenocytes. EcN alone or in combination with ProDer p 1 inhibited the development of airway eosinophilia and neutrophilia. This in vivo protective effect of EcN was, in part, mediated by TLR4 signaling. Our results suggest that EcN represents an efficient adjuvant to prevent allergic responses.     

Population analysis of cellular responses to synthetic peptides of Der p II, a major allerg molecule of Dermatophagoides pteronyssinus, in allergic and nonallergic subjects

Okano M, Nagano T, Kino K, Yasueda H, Baba Y, Saito C, Masuda Y, Ohta N. Population analysis of cellular responses to synthetic peptides of Der p II, a major allergen molecule of Dermatophagoides pteronyssinus , in allergic and nonallergic subjects.
Responses of peripheral blood mononuclear cells to synthetic oligopeptides of Der p II, one of the major allergen molecules of Dermatophagoides pteronyssinus , were compared between allergic and nonallergic subjects. Healthy subjects showed positive responses to crude extracts of D. pteronyssinus , but only allergic subjects showed elevated cellular responses to Der p II. We synthesized three oligopeptides of Der p II in which motifs of a possible T-cell epitopc were included. Of 14 subjects with positive response to Der p II, three responded to all three peptides, while five did not respond to any peptide tested. In 11 allergic patients who showed positive response to Der p II, responsiveness to the peptide K33-T47 was significantly higher than that to other peptides ( P <0.05). All the responding patients were also positive for scratch test to Der p II, suggesting that those epitopcs induced IgE-promoting helper T-cell response in allergic persons. On the other hand, the in vitro cellular responses were not necessarily correlated to IgE production against Der p II in healthy subjects.