Open Access

Immune Responses to Inhalant Allergens

World Allergy Organization Journal20081:97

DOI: 10.1097/WOX.0b013e3181788324

Received: 15 January 2008

Accepted: 1 April 2008

Published: 15 June 2008

Abstract

This overview describes the nature of the immune responses induced by the inhalation of allergens. There is a dichotomy in that B cells have multiple mechanisms that limit the amount of immunoglobulin E (IgE) antibody production, whereas T-cell responses are large even in nonallergic subjects. With the possible exception of responses to cat allergen, however, T cells from nonallergic subjects have limited effector function of helping IgG antibody, and in house-dust mite allergy, this declines with age. Regulation by interleukin 10 (IL-10)-producing cells and CD25+ T-regulatory cells has been proposed, but critically, there is limited evidence for this, and many studies show the highest IL-10 production by cells from allergic subjects. Recent studies have shown the importance of nonlymphoid chemokines thymic stromal lymphopoietin and IL-27, so studying responses in situ is critical. Most sources of allergens have 1 or 2 dominant allergens, and for house-dust mite, it has been shown that people have a predictable responsiveness to high-, mid-and poor-IgE-binding proteins regardless of the total size of their response. This allergen hierarchy can be used to design improved allergen preparations and to investigate how antiallergen responses are regulated.

Keywords

allergens B cells T cells IgG antibody IgE antibody immunoregulation

Immunoglobulin E Responses to Allergens

A hallmark of immediate hypersensitivity is the ability of mast cells and basophils armed with small amounts of immunoglobulin E (IgE) antibody to induce powerful inflammatory reactions. Immunoglobulin E is indeed produced in lower amounts than the more common IgG isotypes. The serum immunoglobulin levels, which vary with atopic status, are in the region of 5 to 500 ng/mL compared with 0.5 and 10 mg/mL of IgG4 and IgG1, respectively. There are few IgE-producing cells, and IgE has a short half-life. Recent studies show that the IgE antibody titers in humans correlate very well with the presence of IgE producing early plasma cells in the blood, [1] suggesting that the IgE response is predominantly caused by short-lived cells, and this is compatible with the diminution of IgE antipollen titers found between pollen seasons. There are at least 2 control points at the molecular level. The rate of translocation of the Vh genes to the 0 gene in class switching is intrinsically weak compared with the switching for gamma subclasses, [2] and RNA transcripts for membrane IgE are unstable compared with the IgG counterparts [3]. At the cellular level, it has been shown in mice that B cells with surface IgE are exceptional because they were largely found outside germinal centers [4]. They arise from a pre-IgE phase, where somatic mutation and affinity maturation take place in IgG1+ cells, and a post-IgE-switching phase, in which IgE cells differentiate swiftly into plasma cells. This leaves a deficiency in IgE-bearing memory cells that would maintain long-lived responses. Studies on the immunoglobulin heavy chain repertoire expressed by antiallergen IgE antibodies show that there are no restrictions with respect to the macroelements of repertoire diversification such as the selection of Vh gene families or VDJ recombinations, [5] but that the responses show a lower repertoire with respect to the number of different Vh genes. Selection from continued exposure to low doses of antigen or limitations of antigen binding imposed by the unique structure of IgE could account for this. For the last possibility, it has been proposed that steric hindrance of antigen binding might occur because IgE has a bent structure that places the Vh region in close proximity to the C-terminal of the constant region [6].

Consistent with tight control mechanisms, it has been repeatedly demonstrated that antiallergen antibodies constitute a large portion of the IgE immunoglobulin [79]. The size of the average IgE antibody response varies with the nature of the allergen source. The serum concentration of IgE antibody binding to the dominant allergens of birch, [10] grass, [11] and mite[12, 13] are about 50 ng/mL, whereas Amb a 1 has been reported as 20 ng/mL, [14] and the cockroach Bla g 2 and 5 have a combined average of 10 ng/mL [15]. Many people have low levels of IgE to cat, [16, 17] so the average anti-Fel d 1 levels are about 4 ng/mL. Some people, however, have very high levels, with more than 100 ng/mL [18]. The Can f 1 dog allergen has comparable IgE titers to Fel d 1, but only a small sample of subjects has been examined [16]. Immunoglobulin E antibodies to the mouse allergen Mus m 1 are also present in small quantities, with an average of about 1 ng/mL in subjects that develop disease after domestic and industrial exposure [19]. There is a possibility that lower evolutionary divergence contributes to lower responses to mammalian allergens, but given that Fel d 1 only has 20% identity with the human uteroglobin homologue, other factors such as the aerodynamics of the allergen may be involved.

The engagement of IgE with the high-affinity FcεR1 in the absence of allergen increases the expression of the receptor on the surface of basophils, mast cells, and dendritic cells, so that the IgE levels, and thus the type of allergen-inducing sensitization, can directly affect the allergic response. It was thought that this occurred by inducing the synthesis of FcεR1, but it now seems to occur via a membrane-stabilizing process [20].

The development of allergic symptoms is related to the titers of antiallergen IgE antibody, but even children with the highest titers only have a 60% probability of disease as shown for wheeze in asthma, and although the probability declined with reduced titers, it was still elevated at the low level of 4.4 ng/mL [21]. The classification of the disease must also be considered. In house dust mite (HDM) allergy, for example, only children with the highest IgE antibody titers have persistent asthma, [22] a very severe form of the disease. Exacerbation of intermittent asthma for example by infection is a more frequent health problem, producing 75% of hospital admissions for asthma in children, [23] and many such children with mite-allergy have quite low titers, less than 10 ng/mL [13].

T-Cell Responses

In contrast to IgE antibody, the T-cell responses to allergens are large. The precursor frequencies of T cells responding to allergen extracts have been reported for pollen[24] and HDM allergy [25, 26]. For mites, the frequencies of T-cell precursors in the peripheral blood were in the range of 0.05% to 0.1% for allergic subjects and 0.01% to 0.02% for nonallergic subjects. Subjects allergic to birch and grass pollen had precursor frequencies with an average of 0.56% for symptomatic subjects and 0.12% for nonallergic nonatopic people. Assing et al [24] also determined the precursor frequencies in people who had skin test reactions but were asymptomatic, finding a frequency of 0.13%, being the same as skin test-negative controls. The asymptomatic skin test-positive people, however, had low levels of IgE antibody and skin test reactivity compared with the symptomatic subjects, so this does not provide information on why some subjects with high levels of sensitization have few symptoms. For comparison with allergens, frequencies in the region of 0.001% for KLH[27] Leishmania[28] and hepatitis B[29] have been found before immunization and rise to about 0.02% after vaccinations. Thus, even nonallergic subjects show a large degree of expansion. The allergen-responsive T cells of allergic subjects are mainly in the memory CD45RO+ population[24, 25] compartment, whereas allergen-responsive cells are found in both the CD45RO+ and CD45RA+ compartments of nonallergic subjects [25]. The induction of the Th2 transcription factor GATA-3 by HDM extract has also been shown to be stronger in CD45RO+ cells [30].

Although most of the T-cell responses in allergy have been studied with extracts, the use of purified allergens is more informative because the stimulating specificities and the concentration used is known and can be accounted for. The T-cell responses to the dominant allergens from grass pollen, [31, 32] birch, [33] weeds, [34, 35] mite, [36] and cat[37] have been studied. The proliferative responses induced in the peripheral blood mononuclear cells (PBMCs) from allergic people are generally better than those of cells from nonallergic people, although there is considerable overlap [36]. The induction of the Th2 cytokines interleukin 5 (IL-5) and IL-13 can be readily detected, [3840] although IL-4 is typically produced in low amounts. Contrary to early observations with extended T-cell culture, PBMCs from allergic subjects show the same amount of interferon-γ (IFN-γ) release as cells from nonallergic subjects as demonstrated with mite[3841]and pollen allergens [24, 41, 42]. Some studies have even shown increased IFN-γ [4345]. The amount of IFN-γ induced by allergens is very similar to that reported to be induced by Th1-type bacterial antigens and vaccines, [4648] so they are not trivial responses. It is likely that the early observations of low IFN-γ from allergic subjects were caused by the potent inhibitory activity of IL-4 on Th1 responses in culture. An interesting observation of Assing et al [49] was that IL-2 was released in excess in cultures of PBMCs from symptomatic pollen-sensitized people and could not be detected in nonsymptomatic and skin test-negative people. Not only is IL-2 produced in larger amounts by Th1 cells, but it is also important for the induction of regulatory T cells.

CD4+ cells have been shown to be the predominant source of Th2 cytokines in PBMCs[50] and to predominate in the cellular infiltrates of airways [51]. The Der p 1 allergen has, however, also been shown to stimulate the release of IFN-γ from CD8+ cells although in in vitro cultures, provided that they were supplemented with IL-2 [43]. In a later article, Der p1-specific CD8 cells were detected by isolating T cells with a major histocompatibility complex class I binding peptide tetramer [52].

Studies on cytokine production in situ have shown that the Th2 polarization is best found in the lungs and not the peripheral blood [53]. Thymic stromal lymphopoietin (TSLP) could have a large effect in the target organ. This epithelial cell product, [54] presumably stimulated by tissue damage, is a powerful inducer of Th2 responses, mediating both expansion and polarization while maintaining the central T-cell memory [55]. It is in turn stimulated by Th2 cytokines and TNF-α and shown to be unaffected by IL-10, IFN-γ, and transforming growth factor-β (TGF-β). Recent studies have identified that T-cell receptor-activated T cells express the TSLP receptor, thus providing a marker for the allergy-mediating cells [56]. This would permit a direct action on T cells as well as the previously known effect via the dendritic cells. The IL-27 secreted by macrophages and dendritic cells may have a reciprocal role, having a potent suppressive action on Th2 as well as Th17 responses [57]. The cytokine bias of T cells in vivo can be tracked to some extent by their chemokine receptors. The Th2 cells preferentially express the chemokine receptors CCR3, CCR4, and CCR8 and migrate to their respective ligands, eotaxin (CCL11), monocyte-derived chemokine (MDC) (CCL22) and thymus- and activation-regulated chemokine (TARC) (CCL17). Bronchial lavages of asthmatic subjects show the accumulation of CCR4+ CD4+ cells and the secretions of the corresponding chemokines TARC and MDC [58]. Endobronchial biopsies after allergen challenge revealed that most of the infiltrating T cells expressed CCR4 with some coexpression of CCR8, and the epithelial cells produced MDC and TARC [59, 60]. The Th1-type IP-10 chemokine can also be produced in asthma, as shown by its production after segmental lung challenges with ragweed, HDM, and cat extracts [61, 62]. Patients who produced late-phase reactions to allergen challenge produce more of both the Th1 and Th2 chemokines [61].

The chemokine receptor bias of allergen-responsive T cells to CCR4 has also been detected in grass pollen allergy [24, 63]. The PBMCs of allergic subjects also preferentially produce the corresponding Th2 TARC and MDC compared with cells from nonallergic people [64, 65]. Recently, pollen allergen-responsive CCR4 cells have been shown to be increased in the pollen season and to be associated with the increased CD62L CD45RO markers for central memory [66]. Allergen-stimulated cells can also be tracked ex vivo by tetramer-binding cells. A study of CD4+ T cells from atopic dermatitis patients with IgE antibody to the cat allergen Fel d 1 used tetramer binding to show a similar result, with most of the T cells being within the central memory compartment [67]. Their frequency was about 0.01% for cells from atopic dermatitis patients and about 0.002% for cells from nonallergic people. Both of these are also high, considering that only 1 epitope bound to 1 HLA-DR molecule was measured. Cat exposure was not reported.

Regulatory T-Cell Responses

There are many observations that show that patients undergoing immunotherapy produce more IL-10 and TGF-β, [68] but it is not clear if these regulators have any control over the development of allergic sensitization. There is considerable significance given to the report by Akdis et al, [41] showing that Der p 1 and pollen allergen-stimulated cells from every nonallergic person examined produced more IL-10 than cells from every allergic person examined. Clear-cut results have not been obtained by other studies. A nonsignificant trend for less IL-10 production by cells from symptomatic cat- and pollen-sensitive children has been reported, [69] but most studies have found that IL-10 is produced in higher amounts by cells from allergic subjects. This has been shown for purified HDM allergens[40, 45, 70] and for cells stimulated with cat and pollen extracts [49, 71, 72]. A study with pure Fel d 1 found that cells from cat-allergic and nonallergic subjects produced the same amount of IL-10, [37] and the latter included people producing IgG4 antibodies. A recent study of Bet v 1 stimulation in birch pollen allergy showed no difference in the IL-10 release induced in cells from allergic and nonallergic subjects, [42] as previously reported by Bullens et al [73]. Bullens et al [73] also found similar levels of IL-10 induced by Der p 2 stimulation [74]. Increased IL-10 has also been found in bronchial and skin challenge sites of HDM allergic people, as indicated by messenger RNA transcription [75].

Evidence that IL-10 might regulate the responses of cells from healthy individuals has been obtained by experiments where the addition of anti-IL-10 receptor antibodies to cultures of their PBMCs enhanced proliferative responses to Der p 1 [76]. This observation was not reproduced in the study with Bet v 1, [42] although anti-IL-10 did increase the production of IFN-γ and TNF-α but not Th2 cytokines. The possibility of a regulatory role for IL-10 in allergic subjects has been indicated in HDM allergy, where patients who produce more IL-10 had smaller wheal sizes in skin prick tests [45, 70]. Opposite to this, however, has been the demonstration that children with early and persistent allergy have more disease and higher Th2 cytokine responses than children with late-onset allergy and that they also have higher IL-10 responses [77].

Suppressive effects of CD4+CD25+ T-regulatory cells have been demonstrated on the proliferation responses of PBMCs cultured with cat and pollen allergens. There was, however, no convincing difference in the activity of cells from allergic and nonallergic subjects[78, 79] or the inhibition of effector events such as cytokine production. The study of Ling et al [78] did show decreased suppression within the pollen season, but because the T-cell responses were much higher than outside of the season, the effect is difficult to interpret. A study of birch allergy outside of the pollen season found that although nonallergic subjects and patients tended to have reduced IL-10 release from the CD25+ cells, it was possible to detect a suppressive activity on T-cell proliferation for the cells from allergic, but not nonallergic, subjects [42]. Inspection of the data, however, suggests that this was caused by uncharacteristically low proliferative responses of the cells from allergic subjects and a higher proliferation of the CD25+ population itself. The Th2 cytokine responses were not affected by the presence of CD25+ cells. Studies of atopic dermatitis showed that HDM extract stimulated more of the regulatory cell transcription factor FOXP3 from PBMCs from HDM-allergic subjects than PBMCs from nonallergic subjects, [80] and that pollen-allergic children have increased numbers of CD4+ CD25+ cells [81]. Studies of T-regulatory cells are, however, clouded by the knowledge that both CD25 and FOXP3 are induced in activated effector and regulatory T cells, albeit transiently [82]. CD4+CD25+ high or bright cells are considered to have high regulatory activity, with few or no effector T cells. However, the CD4+CD25+ high subgroup has been shown to contain a mixture of both regulatory and effector T cells, and the percentage of CD4+CD25 high T cells correlated negatively with the suppressive capacity of CD4+CD25+ T cells [81]. There is an absolute requirement for TGF-β in the development of T-regulatory cells, and the ability of a TGF-β antagonist to increase T-cell proliferative responses to Der p 1 has been reported [76]. Although the experimental studies to date have been inconclusive, an overall role of T-regulatory cells is demonstrated by the increased allergic sensitization in FOXP3-deficient immunodysregulation, polyendocrinopathy, enteropathy, X-linked patients [83].

IgG Antibody Responses

There is good agreement that IgG antibodies to grass, [84] mite, [13, 70, 86] ragweed, [85] and birch[87] allergens are predominantly found in sera of people with IgE antibodies. It therefore appears that although nonsensitized people have T-cell responses to these allergens, they do not make antibody responses of significant magnitude. For mites, some studies with mite extracts have reported pan IgG in nonallergic subjects, but this is difficult to measure, and the method of differentiating from nonspecific binding was not given [88]. Not all allergic people produce IgG, with Hales et al [13] finding IgG in 70% of mite-allergic children but only in 40% of adults. Furthermore, only 25% of children admitted to an emergency department had IgG and the titers were low, suggesting a relationship with susceptibility to exacerbation [13]. Jarvis et al [88] reported an association of IgG4 with symptoms in adults, but this analysis only measured the general association of IgG found in sensitized subjects. The titers of antibodies to the major HDM allergens reach about 0.5 μg/mL for IgG4 and 10 μg/mL for IgG1. These titers are similar to the antibody titers found to a Haemophilus influenzae P6 protein antigen using the same technique and other antibacterial responses [89, 90]. They are however lower than levels that would induce antibody-mediated pneumonitis [91]. Cockroach IgG antibodies are mainly also associated with IgE responses [15]. Grass pollen allergens induce lower IgG antibody titers than mite with mainly IgG4 antibodies at less than 1 μg/mL [92].

Fel d 1 has been reported to induce IgG antibodies in most people exposed to cats[93] possibly because it is present in inhalable air in 50-to 100-fold higher concentrations than mite and pollen allergens [94]. It has been proposed that this tolerizes for IgE while maintaining IgG production [93]. A recent study, however, found that IgG antibodies to cat were 10-fold higher in people with IgE [88]. Mouse allergens have also been reported to induce IgG in nonallergic people in studies of occupational exposure, [95] but data from domestic exposure showed a strong association of IgG antibody with IgE. This may be related to the 50 times lower amounts of Mus m 1 in the air of homes compared with Fel d 1 [95].

Anti-HDM Responses are Hierarchical

Most of the IgE binding to the common sources of allergen is directed to a small number of dominant allergens. Bet v 1 is a very dominant allergen binding 90% of the IgE antibodies to birch pollen in sera from people in Scandinavia [96]. Ole e 1 has a similar dominance for olive pollen, [97] and the group 1 and 5 allergens from grass pollen allergens collectively bind 80% of the IgE in 95% of sera [11]. Amb a 1 is the dominant allergen for ragweed, binding a range from 25% to 85% of the IgE antibodies to pollen extracts [14]. Immunoglobulin E antibodies to Fel d 1 constitute about 50% of the IgE binding to cat dander extracts, [18] although this may not be the major source of all cat allergens [17]. The combination of the group 1 and 2 HDM allergens binds over 50% of the antimite antibodies [12, 13].

To examine the relative binding of the nonmajor mite allergens to the known major Der p 1 and Der p 2 allergens, a panel of 9 allergens was prepared including allergens known to absorb out the IgE binding to nearly all the allergens detectable by IgE immunoblotting of 2-dimensional electrophoresed extracts [98]. The allergens used were either natural allergens or recombinant allergens whose structure had been validated by biochemical function or allergenicity. All the antiallergen antibody measurements were conducted in standardized conditions, so the titers were not influenced by the amount of allergen [13]. There was an excellent correlation of the summated titers of IgE to the different allergens with the values obtained by the Phadebas CAP system with mite extract. Immunoglobulin E antibodies to Der p 1 and 2 made up about 50% of the binding, regardless of the size of the total response or the presence of symptoms. Immunoglobulin E binding to Der p 4, 5, and 7 collectively accounted for 30% of the IgE, and this varied in proportion to the titers to Der p 1 and 2. Binding to Der p 3, 8, 10, and 20 was quantitatively low for nearly all people, although a high frequency of binding was found for some of the allergens. The titers to the midpotency Der p 4, 5, and 7 allergens of 10 ng/mL indicate that they could be important. Comparison with other studies indicates that IgE antibody titers to Der p 6, 9, 13, 16, and 17 will also be very low [99]. Immunoglobulin E binding therefore has a hierarchy that is determined by the allergen. The finding that there is the same hierarchy of response in low and high responders means that different formulations to better represent HDM allergens than extracts can be rationally tested. The IgG antibody response to the allergens shows the same hierarchy as the IgE binding, with the highest titer being found to Der p 1 and 2 followed by Der p 4, 5, and 7. The same mix of IgG1 and the highly Th2-dependent IgG4 antibodies was found. There is at this stage no evidence for a nonallergenic response to poor allergens. A caveat to this study is that allergens of possible importance, namely Der p 11, 14, and 15 have not been studied because they have not been produced or purified in the necessary amounts. The study of the production of mite allergens has shown that poorly allergenic molecules such as mite ferritin, the fatty acid binding protein, tropomyosin, and arginine kinase are produced in larger quantities than the major group 1 and 2 allergens and the midpotency group 4, 5, and 7 allergens [100].

Conclusions

The IgE antibodies induced by allergens are produced in low quantity, and because several features of the B-cell response seem to contribute to this, the system seems tightly regulated. In contrast, the precursor frequency and the amount of cytokine produced by T cells responding to allergens are high and of a similar magnitude to those found for antimicrobial responses. They tend to be higher for allergic compared with nonallergic people, but even the responses of nonsensitized people are similar to those induced by vaccine antigens. The IgG antibody titers are also higher in allergic people, at least for responses to HDM, pollen, and cockroach and mouse allergens. The titers to pollen are small, but the magnitude of the responses to HDM allergens in children are similar to antimicrobial responses and include the IgG1 isotype found in antimicrobial immunity and the highly Th2-dependent IgG4 isotype. Only about 70% of children however produce IgG, and the responses decline with age. It was also found to be severely curtailed in children with intermittent asthma experiencing acute exacerbations. The mechanisms that regulate the IgG responses and perhaps the direct influence of the presence of IgG could therefore be important for disease. The lack of any antibody in nonallergic subjects indicates an inefficient helper T cell function, although allergic and nonallergic subjects have good cytokine responses, as shown by IFN-γ release. The IFN-γ responses of both allergic and nonallergic people are similar and of a similar size to those found in microbial antigens. It is becoming clear that chemokine responses by nonlymphoid cells, especially TSLP and possibly IL-27, are critical regulators of the allergic response, so that responses studied in extended in vitro cultures are not necessarily very informative. Regulatory responses by IL-10-producing cells and CD25+ T-regulatory cells have been proposed as important modifiers of the responses of nonallergic subjects. It is however important to note that the evidence for this is limited, and most studies show that peripheral blood cells from allergic subjects produce more or similar amounts of IL-10 to the cells from nonallergic subjects. This, however, could be the result of an interplay between cytokines in the in vitro culture systems. At least some people exposed to cats make high IgG4 responses to Fel d 1 without the production of IgE antibody, and this could be the result of a regulatory function. It is however possible that the frequency at which this occurs is lower than previously suspected. For HDM allergy, it has been shown that the IgE and IgG responses induced by the different allergens are hierarchical, with the proportion of the response directed to each allergen being similar for all individuals. This not only has use for designing improved allergen preparations, but also can be used as an investigative tool for determining how the responses are controlled.

End note

Supported by the National Health and Medical Research Council of Australia.

Authors’ Affiliations

(1)
Centre for Child Health Research, University of Western Australia, Telethon Institute for Health Research

References

  1. Horst A, Hunzelmann N, Arce S, Herber M, Manz RA, Radbruch A, et al: Detection and characterization of plasma cells in peripheral blood: correlation of IgE+ plasma cell frequency with IgE serum titre. Clin Exp Immunol. 2002, 130: 370-378. 10.1046/j.1365-2249.2002.02025.x.View ArticlePubMedPubMed CentralGoogle Scholar
  2. Jung S, Siebenkotten G, Radbruch A: Frequency of immunoglobulin E class switching is autonomously determined and independent of prior switching to other classes. J Exp Med. 1994, 179: 2023-2026. 10.1084/jem.179.6.2023.View ArticlePubMedGoogle Scholar
  3. Karnowski A, Achatz-Straussberger G, Klockenbusch C, Achatz G, Lamers MC: Inefficient processing of mRNA for the membrane form of IgE is a genetic mechanism to limit recruitment of IgE-secreting cells. Eur J Immunol. 2006, 36: 1917-1925. 10.1002/eji.200535495.View ArticlePubMedGoogle Scholar
  4. Erazo A, Kutchukhidze N, Leung M, Christ AP, Urban JF, Curotto de Lafaille MA, et al: Unique maturation program of the IgE response in vivo. Immunity. 2007, 26: 191-203. 10.1016/j.immuni.2006.12.006.View ArticlePubMedPubMed CentralGoogle Scholar
  5. Andreasson U, Flicker S, Lindstedt M, Valenta R, Greiff L, Korsgren M, et al: The human IgE-encoding transcriptome to assess antibody repertoires and repertoire evolution. J Mol Biol. 2006, 362: 212-227. 10.1016/j.jmb.2006.06.062.View ArticlePubMedGoogle Scholar
  6. Wan T, Beavil RL, Fabiane SM, Beavil AJ, Sohi MK, Keown M, et al: The crystal structure of IgE Fc reveals an asymmetrically bent conformation. Nat Immunol. 2002, 3: 681-686. 10.1038/ni811.View ArticlePubMedGoogle Scholar
  7. Gleich GJ, Jacob GL: Immunoglobulin E antibodies to pollen allergens account for high percentages of total immunoglobulin E protein. Science. 1975, 190: 1106-1108. 10.1126/science.1188389.View ArticlePubMedGoogle Scholar
  8. Chapman MD, Platts-Mills TA: Purification and characterization of the major allergen from Dermatophagoides pteronyssinus-antigen P1. J Immunol. 1980, 125: 587-592.PubMedGoogle Scholar
  9. Eibensteiner P, Spitzauer S, Steinberger P, Kraft D, Valenta R: Immunoglobulin E antibodies of atopic individuals exhibit a broad usage of VH-gene families. Immunology. 2000, 101: 112-119. 10.1046/j.1365-2567.2000.00078.x.View ArticlePubMedPubMed CentralGoogle Scholar
  10. Tresch S, Holzmann D, Baumann S, Blaser K, Wüthrich B, Crameri R, et al: In vitro and in vivo allergenicity of recombinant Bet v 1 compared to the reactivity of natural birch pollen extract. Clin Exp Allergy. 2003, 33: 1153-1158. 10.1046/j.1365-2222.2003.01717.x.View ArticlePubMedGoogle Scholar
  11. Andersson K, Lidholm J: Characteristics and immunobiology of grass pollen allergens. Int Arch Allergy Immunol. 2003, 130: 87-107. 10.1159/000069013.View ArticlePubMedGoogle Scholar
  12. Trombone AP, Tobias KR, Ferriani VP, Schuurman J, Aalberse RC, Smith AM, et al: Use of a chimeric ELISA to investigate immunoglobulin E antibody responses to Der p 1 and Der p 2 in mite-allergic patients with asthma, wheezing and/or rhinitis. Clin Exp Allergy. 2002, 32: 1323-1328. 10.1046/j.1365-2745.2002.01455.x.View ArticlePubMedGoogle Scholar
  13. Hales BJ, Martin AC, Pearce LJ, Laing IA, Hayden CM, Goldblatt J, et al: IgE and IgG anti-house dust mite specificities in allergic disease. J Allergy Clin Immunol. 2006, 118: 361-367. 10.1016/j.jaci.2006.04.001.View ArticlePubMedGoogle Scholar
  14. Zeiss CR, Levitz D, Suszko IM: Quantitation of IgE antibody specific for ragweed and grass allergens: binding of radiolabeled allergens by solid-phase bound IgE. J Allergy Clin Immunol. 1978, 62: 83-90. 10.1016/0091-6749(78)90083-0.View ArticlePubMedGoogle Scholar
  15. Satinover SM, Reefer AJ, Pomes A, Chapman MD, Platts-Mills TA, Woodfolk JA: Specific IgE and IgG antibody-binding patterns to recombinant cockroach allergens. J Allergy Clin Immunol. 2005, 115: 803-809. 10.1016/j.jaci.2005.01.018.View ArticlePubMedGoogle Scholar
  16. Erwin EA, Custis NJ, Satinover SM, Perzanowski MS, Woodfolk JA, Crane J, et al: Quantitative measurement of IgE antibodies to purified allergens using streptavidin linked to a high-capacity solid phase. J Allergy Clin Immunol. 2005, 115: 1029-1035. 10.1016/j.jaci.2004.12.1131.View ArticlePubMedGoogle Scholar
  17. Smith W, Butler AJ, Hazell LA, Chapman MD, Pomés A, Nickels DG, et al: Fel d 4, a cat lipocalin allergen. Clin Exp Allergy. 2004, 34: 1732-1738. 10.1111/j.1365-2222.2004.02090.x.View ArticlePubMedGoogle Scholar
  18. van Ree R, van Leeuwen WA, Bulder I, Bond J, Aalberse RC: Purified natural and recombinant Fel d 1 and cat albumin in in vitro diagnostics for cat allergy. J Allergy Clin Immunol. 1999, 104: 1223-1230. 10.1016/S0091-6749(99)70017-5.View ArticlePubMedGoogle Scholar
  19. Matsui EC, Eggleston PA, Breysse PN, Rand CS, Diette GB: Mouse allergen-specific antibody responses in inner-city children with asthma. J Allergy Clin Immunol. 2007, 119: 910-915. 10.1016/j.jaci.2006.12.663.View ArticlePubMedGoogle Scholar
  20. Kraft S, Kinet JP: New developments in FcepsilonRI regulation, function and inhibition. Nat Rev Immunol. 2007, 7: 365-378. 10.1038/nri2072.View ArticlePubMedGoogle Scholar
  21. Simpson A, Soderstrom L, Ahlstedt S, Murray CS, Woodcock A, Custovic A: IgE antibody quantification and the probability of wheeze in preschool children. J Allergy Clin Immunol. 2005, 116: 744-749. 10.1016/j.jaci.2005.06.032.View ArticlePubMedGoogle Scholar
  22. Shibasaki M, Noguchi E, Takeda K, Takita H: Distribution of IgE and IgG antibody levels against house dust mites in schoolchildren, and their relation with asthma. J Asthma. 1997, 34: 235-242. 10.3109/02770909709068194.View ArticlePubMedGoogle Scholar
  23. Robertson CF, Price D, Henry R, Mellis C, Glasgow N, Fitzgerald D, et al: Short-course montelukast for intermittent asthma in children: a randomized controlled trial. Am J Respir Crit Care Med. 2007, 175: 323-329. 10.1164/rccm.200510-1546OC.View ArticlePubMedGoogle Scholar
  24. Assing K, Nielsen CH, Poulsen LK: Immunological characteristics of subjects with asymptomatic skin sensitization to birch and grass pollen. Clin Exp Allergy. 2006, 36: 283-292. 10.1111/j.1365-2222.2006.02435.x.View ArticlePubMedGoogle Scholar
  25. Richards D, Chapman MD, Sasama J, Lee TH, Kemeny DM: Immune memory in CD4+ CD45RA+ T cells. Immunology. 1997, 91: 331-339. 10.1046/j.1365-2567.1997.00274.x.View ArticlePubMedPubMed CentralGoogle Scholar
  26. Burastero SE, Fenoglio D, Crimi E, Brusasco V, Rossi GA: Frequency of allergen-specific T lymphocytes in blood and bronchial response to allergen in asthma. J Allergy Clin Immunol. 1993, 91: 1075-1081. 10.1016/0091-6749(93)90222-2.View ArticlePubMedGoogle Scholar
  27. Ford D, Burger D: Precursor frequency of antigen-specific T cells: effects of sensitization in vivo and in vitro. Cell Immunol. 1983, 79: 334-344. 10.1016/0008-8749(83)90075-8.View ArticlePubMedGoogle Scholar
  28. Gabaglia CR, Valle MT, Fenoglio D, Barcinski MA, Manca F: CD4(+) T cell response to Leishmania spp in non-infected individuals. Hum Immunol. 2000, 61: 531-537. 10.1016/S0198-8859(00)00119-1.View ArticlePubMedGoogle Scholar
  29. Avanzini MA, Belloni C, Soncini R, Ciardelli L, de Silvestri A, Pistorio A, et al: Increment of recombinant hepatitis B surface antigen-specific T-cell precursors after revaccination of slow responder children. Vaccine. 2001, 19: 2819-2824. 10.1016/S0264-410X(01)00007-X.View ArticlePubMedGoogle Scholar
  30. Macaubas C, Lee PT, Smallacombe TB, Holt BJ, Wee C, Sly PD, et al: Reciprocal patterns of allergen-induced GATA-3 expression in peripheral blood mononuclear cells from atopics vs non-atopics. Clin Exp Allergy. 2002, 32: 97-106. 10.1046/j.0022-0477.2001.01288.x.View ArticlePubMedGoogle Scholar
  31. van Neerven R, Wissenbach M, Ipsen H, Bufe A, Arnved J, Wurtzen PA: Differential recognition of recombinant Phl p 5 isoallergens by Phl p 5-specific T cells. Int Arch Allergy Immunol. 1999, 118: 125-128. 10.1159/000024047.View ArticlePubMedGoogle Scholar
  32. Burton MD, Papalia L, Eusebius NP, O'Hehir RE, Rolland JM: Characterization of the human T cell response to rye grass pollen allergens Lol p 1 and Lol p 5. Allergy. 2002, 57: 1136-1144. 10.1034/j.1398-9995.2002.23699.x.View ArticlePubMedGoogle Scholar
  33. Ebner C, Schenk S, Najafian N, Siemann U, Steiner R, Fischer GW, et al: Nonallergic individuals recognize the same T cell epitopes of Bet v 1, the major birch pollen allergen, as atopic patients. J Immunol. 1995, 154: 1932-1940.PubMedGoogle Scholar
  34. Jahn-Schmid B, Fischer GF, Bohle B, Faé I, Gadermaier G, Dedic A, et al: Antigen presentation of the immunodominant T-cell epitope of the major mugwort pollen allergen, Art v 1, is associated with the expression of HLA-DRB1 *01. J Allergy Clin Immunol. 2005, 115: 399-404. 10.1016/j.jaci.2004.10.010.View ArticlePubMedGoogle Scholar
  35. Eisenbrey AB, Agarwal MK, Offord KP, Adolphson CR, Yunginger JW, Gleich GJ: Seasonal variation of in vitro lymphocyte proliferative response to ragweed antigen E. J Allergy Clin Immunol. 1985, 75: 84-90. 10.1016/0091-6749(85)90017-X.View ArticlePubMedGoogle Scholar
  36. O'Brien RM, Thomas WR, Wootton AM: T cell responses to the purified major allergens from the house dust mite Dermatophagoides pteronyssinus. J Allergy Clin Immunol. 1992, 89: 1021-1031. 10.1016/0091-6749(92)90225-Q.View ArticlePubMedGoogle Scholar
  37. Reefer AJ, Carneiro RM, Custis NJ, Platts-Mills TA, Sung SS, Hammer J, et al: A role for IL-10-mediated HLA-DR7-restricted T cell-dependent events in development of the modified Th2 response to cat allergen. J Immunol. 2004, 172: 2763-2772.View ArticlePubMedGoogle Scholar
  38. Li Y, Simons FE, Jay FT, HayGlass KT: Allergen-driven limiting dilution analysis of human IL-4 and IFN-gamma production in allergic rhinitis and clinically tolerant individuals. Int Immunol. 1996, 8: 897-904. 10.1093/intimm/8.6.897.View ArticlePubMedGoogle Scholar
  39. Hales BJ, Shen H, Thomas WR: Cytokine responses to Der p 1 and Der p 7: house dust mite allergens with different IgE-binding activities. Clin Exp Allergy. 2000, 30: 934-943. 10.1046/j.1365-2222.2000.00901.x.View ArticlePubMedGoogle Scholar
  40. Hales BJ, Hazell LA, Smith W, Thomas WR: Genetic variation of Der p 2 allergens: effects on T cell responses and immunoglobulin E binding. Clin Exp Allergy. 2002, 32: 1461-1467. 10.1046/j.1365-2745.2002.01500.x.View ArticlePubMedGoogle Scholar
  41. Akdis M, Verhagen J, Taylor A, Karamloo F, Karagiannidis C, Crameri R, et al: Immune responses in healthy and allergic individuals are characterized by a fine balance between allergen-specific T regulatory 1 and T helper 2 cells. J Exp Med. 2004, 199: 1567-1575. 10.1084/jem.20032058.View ArticlePubMedPubMed CentralGoogle Scholar
  42. Thunberg S, Akdis M, Akdis CA, Grönneberg R, Malmström V, Trollmo C, et al: Immune regulation by CD4(+)CD25(+) T cells and interleukin-10 in birch pollen-allergic patients and non-allergic controls. Clin Exp Allergy. 2007, 37: 1127-1136. 10.1111/j.1365-2222.2007.02739.x.View ArticlePubMedGoogle Scholar
  43. O'Brien RM, Xu H, Rolland JM, Byron KA, Thomas WR: Allergen-specific production of interferon-gamma by peripheral blood mononuclear cells and CD8 T cells in allergic disease and following immunotherapy. Clin Exp Allergy. 2000, 30: 333-340. 10.1046/j.1365-2222.2000.00700.x.View ArticlePubMedGoogle Scholar
  44. Smart JM, Kemp AS: Increased Th1 and Th2 allergen-induced cytokine responses in children with atopic disease. Clin Exp Allergy. 2002, 32: 796-802. 10.1046/j.1365-2222.2002.01391.x.View ArticlePubMedGoogle Scholar
  45. Heaton T, Rowe J, Turner S, Aalberse RC, de Klerk N, Suriyaarachchi D, et al: An immunoepidemiological approach to asthma: identification of in-vitro T-cell response patterns associated with different wheezing phenotypes in children. Lancet. 2005, 365: 142-149. 10.1016/S0140-6736(05)17704-6.View ArticlePubMedGoogle Scholar
  46. Holt PG, Rudin A, Macaubas C, Holt BJ, Rowe J, Loh R, et al: Development of immunologic memory against tetanus toxoid and pertactin antigens from the diphtheria-tetanus-pertussis vaccine in atopic versus nonatopic children. J Allergy Clin Immunol. 2000, 105: 1117-1122. 10.1067/mai.2000.105804.View ArticlePubMedGoogle Scholar
  47. Epton MJ, Hales BJ, Thompson PJ, Thomas WR: T cell cytokine responses to outer membrane proteins of Haemophilus influenzae and the house dust mite allergens Der p 1 in allergic and non-allergic subjects. Clin Exp Allergy. 2002, 32: 1589-1595. 10.1046/j.1365-2222.2002.01523.x.View ArticlePubMedGoogle Scholar
  48. Laaksonen K, Waris M, Makela MJ, Terho EO, Savolainen J: In vitro kinetics of allergen- and microbe-induced IL-4 and IFN-gamma mRNA expression in PBMC of pollen-allergic patients. Allergy. 2003, 58: 62-66. 10.1034/j.1398-9995.2003.23653.x.View ArticlePubMedGoogle Scholar
  49. Assing K, Bodtger U, Poulsen LK: Seasonal dynamics of chemokine receptors and CD62L in subjects with asymptomatic skin sensitization to birch and grass pollen. Allergy. 2006, 61: 759-768. 10.1111/j.1398-9995.2006.01084.x.View ArticlePubMedGoogle Scholar
  50. Till S, Durham S, Dickason R, Huston D, Bungre J, Walker S, et al: IL-13 production by allergen-stimulated T cells is increased in allergic disease and associated with IL-5 but not IFN-gamma expression. Immunology. 1997, 91: 53-57. 10.1046/j.1365-2567.1997.00218.x.View ArticlePubMedPubMed CentralGoogle Scholar
  51. Frew AJ, Kay AB: The pattern of human late-phase skin reactions to extracts of aeroallergens. J Allergy Clin Immunol. 1988, 81: 1117-1121. 10.1016/0091-6749(88)90878-0.View ArticlePubMedGoogle Scholar
  52. Seneviratne SL, Jones L, King AS, Black A, Powell S, McMichael AJ, et al: Allergen-specific CD8(+) T cells and atopic disease. J Clin Invest. 2002, 110: 1283-1291.View ArticlePubMedPubMed CentralGoogle Scholar
  53. Cho SH, Stanciu LA, Holgate ST, Johnston SL: Increased interleukin-4, interleukin-5, and interferon-gamma in airway CD4+ and CD8+ T cells in atopic asthma. Am J Respir Crit Care Med. 2005, 171: 224-230. 10.1164/rccm.200310-1416OC.View ArticlePubMedGoogle Scholar
  54. Allakhverdi Z, Comeau MR, Jessup HK, Yoon BR, Brewer A, Chartier S, et al: Thymic stromal lymphopoietin is released by human epithelial cells in response to microbes, trauma, or inflammation and potently activates mast cells. J Exp Med. 2007, 204: 253-258. 10.1084/jem.20062211.View ArticlePubMedPubMed CentralGoogle Scholar
  55. Wang YH, Ito T, Wang YH, Homey B, Watanabe N, Martin R, et al: Maintenance and polarization of human Th2 central memory T cells by thymic stromal lymphopoietin-activated dendritic cells. Immunity. 2006, 24: 827-838. 10.1016/j.immuni.2006.03.019.View ArticlePubMedGoogle Scholar
  56. Rochman I, Watanabe N, Arima K, Liu YJ, Leonard WJ: Cutting edge: direct action of thymic stromal lymphopoietin on activated human CD4+ T cells. J Immunol. 2007, 178: 6720-6724.View ArticlePubMedGoogle Scholar
  57. Batten M, Ghilardi N: The biology and therapeutic potential of interleukin 27. J Mol Med. 2007, 85: 661-672. 10.1007/s00109-007-0164-7.View ArticlePubMedGoogle Scholar
  58. Hartl D, Griese M, Nicolai T, Zissel G, Prell C, Konstantopoulos N, et al: Pulmonary chemokines and their receptors differentiate children with asthma and chronic cough. J Allergy Clin Immunol. 2005, 115: 728-736. 10.1016/j.jaci.2004.11.049.View ArticlePubMedGoogle Scholar
  59. Panina-Bordignon P, Papi A, Mariani M, Di Lucia P, Casoni G, Bellettato C, et al: The C-C chemokine receptors CCR4 and CCR8 identify airway T cells of allergen-challenged atopic asthmatics. J Clin Invest. 2001, 107: 1357-1364. 10.1172/JCI12655.View ArticlePubMedPubMed CentralGoogle Scholar
  60. Kallinich T, Schmidt S, Hamelmann E, Fischer A, Qin S, Luttmann W, et al: Chemokine-receptor expression on T cells in lung compartments of challenged asthmatic patients. Clin Exp Allergy. 2005, 35: 26-33. 10.1111/j.1365-2222.2004.02132.x.View ArticlePubMedGoogle Scholar
  61. Liu L, Jarjour NN, Busse WW, Kelly EA: Enhanced generation of helper T type 1 and 2 chemokines in allergen-induced asthma. Am J Respir Crit Care Med. 2004, 169: 1118-1124. 10.1164/rccm.200312-1659OC.View ArticlePubMedGoogle Scholar
  62. Bochner BS, Hudson SA, Xiao HQ, Liu MC: Release of both CCR4-active and CXCR3-active chemokines during human allergic pulmonary late-phase reactions. J Allergy Clin Immunol. 2003, 112: 930-934. 10.1016/j.jaci.2003.08.012.View ArticlePubMedGoogle Scholar
  63. Nouri-Aria KT, Wilson D, Francis JN, Jopling LA, Jacobson MR, Hodge MR, et al: CCR4 in human allergen-induced late responses in the skin and lung. Eur J Immunol. 2002, 32: 1933-1938. 10.1002/1521-4141(200207)32:7<1933::AID-IMMU1933>3.0.CO;2-R.View ArticlePubMedGoogle Scholar
  64. Simons FE, Shikishima Y, Van Nest G, Eiden JJ, HayGlass KT: Selective immune redirection in humans with ragweed allergy by injecting Amb a 1 linked to immunostimulatory DNA. J Allergy Clin Immunol. 2004, 113: 1144-1151. 10.1016/j.jaci.2004.03.003.View ArticlePubMedGoogle Scholar
  65. Thottingal TB, Stefura BP, Simons FE, Bannon GA, Burks W, HayGlass KT: Human subjects without peanut allergy demonstrate T cell-dependent, Th2-biased, peanut-specific cytokine and chemokine responses independent of Th1 expression. J Allergy Clin Immunol. 2006, 118: 905-914. 10.1016/j.jaci.2006.06.016.View ArticlePubMedGoogle Scholar
  66. Moulton VR, Bushar ND, Leeser DB, Patke DS, Farber DL: Divergent generation of heterogeneous memory CD4 T cells. J Immunol. 2006, 177: 869-876.View ArticlePubMedGoogle Scholar
  67. Bateman EA, Ardern-Jones MR, Ogg GS: Persistent central memory phenotype of circulating Fel d 1 peptide/DRB1*0101 tetramer-binding CD4+ T cells. J Allergy Clin Immunol. 2006, 118: 1350-1356. 10.1016/j.jaci.2006.07.040.View ArticlePubMedGoogle Scholar
  68. Taylor A, Verhagen J, Blaser K, Akdis M, Akdis CA: Mechanisms of immune suppression by interleukin-10 and transforming growth factor-beta: the role of T regulatory cells. Immunology. 2006, 117: 433-442. 10.1111/j.1365-2567.2006.02321.x.View ArticlePubMedPubMed CentralGoogle Scholar
  69. Jenmalm MC, Van Snick J, Cormont F, Salman B: Allergen-induced Th1 and Th2 cytokine secretion in relation to specific allergen sensitization and atopic symptoms in children. Clin Exp Allergy. 2001, 31: 1528-1535. 10.1046/j.1365-2222.2001.01190.x.View ArticlePubMedGoogle Scholar
  70. Macaubas C, Sly PD, Burton P, Tiller K, Yabuhara A, Holt BJ, et al: Regulation of T-helper cell responses to inhalant allergen during early childhood. Clin Exp Allergy. 1999, 29: 1223-1231. 10.1046/j.1365-2222.1999.00654.x.View ArticlePubMedGoogle Scholar
  71. Matsumoto K, Gauvreau GM, Rerecich T, Watson RM, Wood LJ, O'Byrne PM: IL-10 production in circulating T cells differs between allergen-induced isolated early and dual asthmatic responders. J Allergy Clin Immunol. 2002, 109: 281-286. 10.1067/mai.2002.121144.View ArticlePubMedGoogle Scholar
  72. Imada M, Simons FE, Jay FT, HayGlass KT: Antigen mediated and polyclonal stimulation of human cytokine production elicit qualitatively different patterns of cytokine gene expression. Int Immunol. 1995, 7: 229-237. 10.1093/intimm/7.2.229.View ArticlePubMedGoogle Scholar
  73. Bullens DM, Van Den Keybus C, Dilissen E, Kasran A, Ceuppens JL: Allergen-specific T cells from birch-pollen-allergic patients and healthy controls differ in T helper 2 cytokine and in interleukin-10 production. Clin Exp Allergy. 2004, 34: 879-887. 10.1111/j.1365-2222.2004.01955.x.View ArticlePubMedGoogle Scholar
  74. Bullens DM, De Swerdt A, Dilissen E, Kasran A, Kroczek RA, Cadot P, et al: House dust mite-specific T cells in healthy non-atopic children. Clin Exp Allergy. 2005, 35: 1535-1541. 10.1111/j.1365-2222.2005.02352.x.View ArticlePubMedGoogle Scholar
  75. Robinson DS, Tsicopoulos A, Meng Q, Durham S, Kay AB, Hamid Q: Increased interleukin-10 messenger RNA expression in atopic allergy and asthma. Am J Respir Cell Mol Biol. 1996, 14: 113-117. 10.1165/ajrcmb.14.2.8630259.View ArticlePubMedGoogle Scholar
  76. Jutel M, Akdis M, Budak F, Aebischer-Casaulta C, Wrzyszcz M, Blaser K, et al: IL-10 and TGF-beta cooperate in the regulatory T cell response to mucosal allergens in normal immunity and specific immunotherapy. Eur J Immunol. 2003, 33: 1205-1214. 10.1002/eji.200322919.View ArticlePubMedGoogle Scholar
  77. Turner SW, Heaton T, Rowe J, Suriyaarachchi D, Serralha M, Holt BJ, et al: Early-onset atopy is associated with enhanced lymphocyte cytokine responses in 11-year-old children. Clin Exp Allergy. 2007, 37: 371-380. 10.1111/j.1365-2222.2007.02668.x.View ArticlePubMedGoogle Scholar
  78. Ling EM, Smith T, Nguyen XD, Pridgeon C, Dallman M, Arbery J, et al: Relation of CD4+CD25+ regulatory T-cell suppression of allergen-driven T-cell activation to atopic status and expression of allergic disease. Lancet. 2004, 363: 608-615. 10.1016/S0140-6736(04)15592-X.View ArticlePubMedGoogle Scholar
  79. Bellinghausen I, Klostermann B, Knop J, Saloga J: Human CD4+CD25+ T cells derived from the majority of atopic donors are able to suppress Th1 and Th2 cytokine production. J Allergy Clin Immunol. 2003, 111: 862-868. 10.1067/mai.2003.1412.View ArticlePubMedGoogle Scholar
  80. Taylor AL, Hale J, Hales BJ, Dunstan JA, Thomas WR, Prescott SL: FOXP3 mRNA expression at 6 months of age is not affected by giving probiotics from birth, but is higher in infants who develop atopic dermatitis. Pediatr Allergy Immunol. 2007, 18: 10-19.View ArticlePubMedGoogle Scholar
  81. Jartti T, Burmeister KA, Seroogy CM, Jennens-Clough ML, Tisler CJ, Salazar LP, et al: Association between CD4(+)CD25(high) T cells and atopy in children. J Allergy Clin Immunol. 2007, 120: 177-183. 10.1016/j.jaci.2007.03.008.View ArticlePubMedGoogle Scholar
  82. Zheng Y, Rudensky AY: Foxp3 in control of the regulatory T cell lineage. Nat Immunol. 2007, 8: 457-462. 10.1038/ni1455.View ArticlePubMedGoogle Scholar
  83. Wildin RS, Smyk-Pearson S, Filipovich AH: Clinical and molecular features of the immunodysregulation, polyendocrinopathy, enteropathy, X linked (IPEX) syndrome. J Med Gen. 2002, 39: 537-545. 10.1136/jmg.39.8.537.View ArticleGoogle Scholar
  84. Platts-Mills TA: Local production of IgG, IgA and IgE antibodies in grass pollen hay fever. J Immunol. 1979, 122: 2218-2225.PubMedGoogle Scholar
  85. Platts-Mills TA, von Maur RK, Ishizaka K, Norman PS, Lichtenstein LM: IgA and IgG anti-ragweed antibodies in nasal secretions. Quantitative measurements of antibodies and correlation with inhibition of histamine release. J Clin Invest. 1976, 57: 1041-1050. 10.1172/JCI108346.View ArticlePubMedPubMed CentralGoogle Scholar
  86. Chapman MD, Platts-Mills TA: Measurement of IgG, IgA and IgE antibodies to Dermatophagoides pteronyssinus by antigen-binding assay, using a partially purified fraction of mite extract (F4P1). Clin Exp Immunol. 1978, 34: 126-136.PubMedPubMed CentralGoogle Scholar
  87. Benson M, Reinholdt J, Cardell LO: Allergen-reactive antibodies are found in nasal fluids from patients with birch pollen-induced intermittent allergic rhinitis, but not in healthy controls. Allergy. 2003, 58: 386-392. 10.1034/j.1398-9995.2003.00113.x.View ArticlePubMedGoogle Scholar
  88. Jarvis D, Zock JP, Heinrich J, Svanes C, Verlato G, Olivieri M, et al: Cat and dust mite allergen levels, specific IgG and IgG4, and respiratory symptoms in adults. J Allergy Clin Immunol. 2007, 119: 697-704. 10.1016/j.jaci.2006.10.042.View ArticlePubMedGoogle Scholar
  89. Vance E, George S, Guinan EC, Wheeler C, Antin JH, Ambrosino DM, et al: Comparison of multiple immunization schedules for Haemophilus influenzae type b-conjugate and tetanus toxoid vaccines following bone marrow transplantation. Bone Marrow Transplant. 1998, 22: 735-741. 10.1038/sj.bmt.1701424.View ArticlePubMedGoogle Scholar
  90. Quinn CP, Dull PM, Semenova V, Li H, Crotty S, Taylor TH, et al: Immune responses to Bacillus anthracis protective antigen in patients with bioterrorism-related cutaneous or inhalation anthrax. J Infect Dis. 2004, 190: 1228-1236. 10.1086/423937.View ArticlePubMedGoogle Scholar
  91. McSharry C, Dye GM, Ismail T, Anderson K, Spiers EM, Boyd G: Quantifying serum antibody in bird fanciers' hypersensitivity pneumonitis. BMC Pulm Med. 2006, 6: 16-24. 10.1186/1471-2466-6-16.View ArticlePubMedPubMed CentralGoogle Scholar
  92. Rossi RE, Monasterolo G: Evaluation of recombinant and native timothy pollen (rPhl p 1, 2, 5, 6, 7, 11, 12 and nPhl p 4)-specific IgG4 antibodies induced by subcutaneous immunotherapy with timothy pollen extract in allergic patients. Int Arch Allergy Immunol. 2004, 135: 44-53. 10.1159/000080042.View ArticlePubMedGoogle Scholar
  93. Platts-Mills T, Vaughan J, Squillace S, Woodfolk J, Sporik R: Sensitisation, asthma, and a modified Th2 response in children exposed to cat allergen: a population-based cross-sectional study. Lancet. 2001, 357: 752-756. 10.1016/S0140-6736(00)04168-4.View ArticlePubMedGoogle Scholar
  94. Custis NJ, Woodfolk JA, Vaughan JW, Platts-Mills TA: Quantitative measurement of airborne allergens from dust mites, dogs, and cats using an ion-charging device. Clin Exp Allergy. 2003, 33: 986-991. 10.1046/j.1365-2222.2003.01706.x.View ArticlePubMedGoogle Scholar
  95. Matsui EC, Diette GB, Krop EJ, Aalberse RC, Smith AL, Eggleston PA: Mouse allergen-specific immunoglobulin G4 and risk of mouse skin test sensitivity. Clin Exp Allergy. 2006, 36: 1097-1103. 10.1111/j.1365-2222.2006.02534.x.View ArticlePubMedGoogle Scholar
  96. Movérare R, Westritschnig K, Svensson M, Hayek B, Bende M, Pauli G, et al: Different IgE reactivity profiles in birch pollen-sensitive patients from six European populations revealed by recombinant allergens: an imprint of local sensitization. Int Arch Allergy Immunol. 2002, 128: 325-335. 10.1159/000063855.View ArticlePubMedGoogle Scholar
  97. Rodriguez R, Villalba M, Batanero E, Palomares O, Salamanca G: Emerging pollen allergens. Biomed Pharmacother. 2007, 61: 1-7. 10.1016/j.biopha.2006.09.014.View ArticlePubMedGoogle Scholar
  98. Weghofer M, Thomas WR, Pittner G, Horak F, Valenta R, Vrtala S: Comparison of purified Dermatophagoides pteronyssinus allergens and extract by two-dimensional immunoblotting and quantitative immunoglobulin E inhibitions. Clin Exp Allergy. 2005, 35: 1384-1391. 10.1111/j.1365-2222.2005.02345.x.View ArticlePubMedGoogle Scholar
  99. Thomas WR, Hales BJ: T and B-cell responses to HDM allergens. Immunol Res. 2007, 37: 187-199. 10.1007/BF02697369.View ArticlePubMedGoogle Scholar
  100. Batard T, Hrabina A, Bi XZ, Chabre H, Lemoine P, Couret MN, et al: Production and proteomic characterization of pharmaceutical-grade Dermatophagoides pteronyssinus and Dermatophagoides farinae extracts for allergy vaccines. Int Arch Allergy Immunol. 2006, 140: 295-305. 10.1159/000093707.View ArticlePubMedGoogle Scholar

Copyright

© World Allergy Organization; licensee BioMed Central Ltd. 2008

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.