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Désensibilisation pollinique et allergie alimentaire
mercredi 9 janvier 2008, par
Pour les aliments dont la réactivité est induite par une sensibilisation pollinique, on peut espérer qu’une immunothérapie de la pollinose va corriger à la fois les symptômes respiratoires et oculaires (rhino-conjonctivite, asthme) mais aussi les symptômes alimentaires (avant tout le syndrome oral).
Des résultats contradictoires ont été relevés : certains auteurs concluent à un effet bénéfique de l’immunothérapie (IT) sur l’allergie alimentaire, tandis que d’autres estiment que la faiblesse des résultats obtenus ne justifient pas, en tout cas, une indication de désensibilisation ayant pour objectif de corriger un syndrome oral.
C’est principalement l’IT d’une pollinose au bouleau qui a été étudiée. Cela tient notamment à la fréquence des réactions alimentaires induites par ce pollen (pomme, noisette, etc…). Comme le souligne Van Ree 
, trop peu de ces travaux ont un protocole rigoureux (groupe placebo, voire groupe témoin sans IT ; TPO en double aveugle).
D’autres paramètres rendent le rapprochement des résultats difficiles : durée de l’IT, pays d’origine, voie de l’IT. Sur ce dernier point on manque de travaux avec la voie sublinguale, la grande majorité des résultats publiés concernant la voie sous-cutanée.
Le tableau ci-dessous présente les résultats obtenus avec une IT bouleau (ou Bétulacées).
Ref : 1 2 3 4 5 6 7 8
Sur 8 études, 4 concluent à un effet bénéfique de l’IT bouleau sur le syndrome oral associé (pomme, noisette,…) tandis que les 4 autres ont un avis contraire ou peu positif .
Pour Asero , le résultat est d’autant plus net que la réactivité en TC pour la pomme est faible avant le début de l’IT.
La correction partielle, ou parfois totale, du syndrome oral persiste-t-elle à distance de la fin de l’IT ?
- Asero a suivi pendant environ 3 ans des sujets ayant présenté un TPO négatif pour la pomme en fin d’IT
- il observe en TP ouvert une rechute chez 10 % des sujets (n = 30) à + 6 mois, 23 % à + 18 mois et 39 % à + 30 mois.
L’effet bénéfique de l’IT a donc été conservé pour environ 60 % des sujets. Mais le devenir à plus long terme n’est pas étudié. Il faudrait, par ailleurs, d’autres travaux concernant le suivi des patients.
Le cas d’une patiente allergique au kiwi étudié par Mempel est un peu différent, même si l’effet sur l’allergie alimentaire persistait 5 ans après le début de l’IT : il s’agissait d’une désensibilisation par voie sublinguale avec le kiwi lui-même.
- Ce cas clinique souligne par ailleurs les effets sensibilisants éventuels de toute IT : la patiente a vu se développer avec l’IT une réactivité cutanée (mais pas d’allergie) pour le bouleau et le latex .
Des néo-allergies provoquées par une IT ont été rapportées : 3 cas pour le céleri parmi 20 IT armoise , 1 cas pour la jujube après ITSL latex , 4 cas de syndrome oral parmi 57 désensibilisations pour graminées et/ou bouleau ou armoise . Ajoutés aux quelques cas de positivation décrits dans le tableau ci-dessus concernant l’IT bouleau, ces néo-allergies représentent une réalité clinique dont la portée reste cependant mal définie : la vérification par TPO a rarement été menée et le nombre de cas est minime.
Les mêmes remarques s’appliquent aux effets d’une IT acariens vis à vis des mollusques comme l’escargot ou vis à vis des crevettes (cf. escargots, cf. crustacés, cf. mollusques marins).
Les pollens de graminées ont aussi été étudiés.
Ces pollens sont responsables de réactions alimentaires beaucoup moins nettes que celles induites par le pollen de bouleau.
Aussi, des modifications de réactivité clinique ont rarement été relevées avec les IT graminées. D’autant que dans de nombreux travaux, les graminées étaient associées à 1 ou d’autres pollens :
- Asero rapporte une guérison d’allergie alimentaire (fenouil, concombre, melon) avec une IT graminées + armoise + ambroisie
- Kelso rapporte aussi la guérison d’allergie à divers aliments avec une IT graminées + un mélange d’arbres
- Baumann note une amélioration du syndrome oral chez 53 % des patients sous IT graminées et/ou bouleau ; et observe que le bouleau seul est plus efficace que l’association bouleau + graminées
- Bilo relève 3 améliorations du syndrome oral parmi 57 patients sous IT graminées et/ou bouleau ou ambroisie. Parallèlement 3 néo-allergies alimentaires sont apparues, toutes avec une IT bouleau
- Asero trouve autant de néo-réactivités pour des pollens jusque-là négatifs en TC chez les sujets sous IT (11 %) que dans le groupe contrôle (10 %).
L’ambroisie a été étudiée aussi par Nowak-Wegzyn en association avec le bouleau avec une amélioration pour la pomme et le melon.
Alonso a étudié l’effet d’une IT platane et observé une amélioration de la dose tolérée en TPO ouvert chez 6 des 11 sujets (noisette, noix, pêche,….).
D’autres travaux ont regardé les effets de l’IT sur la réactivité in vitro. Bien qu’une positivation in vitro pour tel ou tel allergène n’ait qu’une signification clinique très hypothétique, ces études sont intéressantes sur le plan immunologique :
- Ball relève une néo-réactivité pour certains épitopes de Phl p 1 sous IT graminées
- Van Ree note 5 cas de positivation pour certains allergènes d’ivraie parmi 64 sujets sous IT graminées.
- Mari trouve une prévalence plus élevée de résultats positifs pour différents allergènes recombinants de fléole dans une cohorte ayant reçu une IT graminées. Par exemple, la polcalcine rPhl p 7 est positive chez 50 % de ces sujets contre 15 % dans une population témoin.
- Rossi a étudié aussi des recombinants de fléole mais cette fois en comparant les résultats avant et après IT fléole : il n’a pas observé de néo-réactivités, les sujets positifs après IT étaient déjà positifs pour le même allergène avant IT
- Aberer n’observe pas non plus de néo-réactivité pour rPhl p 7 ou rPhl p 12 (profiline) après IT orale au pollen de fléole.
- Enfin Mattson note 3 positivations pour rBet v 2 parmi 9 patients sous IT bouleau 2-3 ans. Ces 3 sujets ont vu aussi se positiver rBet v 4 (polcalcine) (1 cas) ou rBet v 6 (isoflavone réductase) (1 cas). Comparativement, parmi 4 sujets non traités par IT, 1 cas de positivation pour rBet v 2 a été relevé.
Au total, la désensibilisation pollinique est capable d’induire des néo-réactivités vis à vis d’allergènes présents dans l’extrait utilisé pour l’IT ou vis à vis d’allergènes croisants présents dans d’autres produits (autres pollens, aliments).
Ces néo-réactivités ont une relevance clinique incertaine, tant par le manque d’études fiables que par la quasi-absence de travaux cherchant à contrôler l’effet à plus long terme.
Globalement, les cas de néo-allergie alimentaire restent peu nombreux, en nombre plus faible que ceux d’une amélioration d’une allergie alimentaire pré-existante.
Les bénéfices indirects d’une IT sur l’allergie alimentaire semblent donc plus grands que les risques de néo-allergie.
Cependant, les effets de l’IT apportent rarement une "guérison" de l’allergie alimentaire et, pour certains auteurs, l’IT ne peut se justifier comme indication pour traiter une allergie alimentaire induite par la pollinose.
[1] - van Ree R. Clinical importance of cross-reactivity in food allergy. Curr Opin Allergy Clin Immunol 2004;4:235-240
PURPOSE OF REVIEW: Review of recent developments in the field of cross-reactivity in food allergy and the clinical relevance of these developments. RECENT FINDINGS: New foods have been added to the list of Bet v 1 and profilin-related food allergies. Clinical relevance of cross-reactions based on recognition of carbohydrate determinants and profilin is limited for the population of pollen-allergic patients as a whole. For selected food allergic patients, however, N-glycans and particularly profilin are potentially of clinical relevance. Lipid transfer proteins have further been established as clinically more severe allergens in several foods. This severity is attributed to their stability to proteolysis and processing. Storage proteins of several nuts and seeds have been identified as important allergens, but cross-reactivity between storage proteins of different foods appears to be limited. Using cross-reactivity as the basis for immunotherapy in food allergy seems promising but needs confirmation by double-blind, placebo-controlled trials. SUMMARY: The continued identification and characterization of cross-reactive allergens facilitates the study of factors determining clinical relevance of cross-reactivity and of possible efficacy of immunotherapy in food allergy.
↩[2] - Möller C. Effect of pollen immunotherapy on food hypersensitivity in children with birch pollinosis. Ann Allergy 1989;62:343-345
Of 72 children with severe rhinoconjunctivitis due to birch pollinosis, 67 (93%) reported sensitivity against nuts, apples, etc. The hayfever symptoms improved by immunotherapy but neither subcutaneous (n = 42) nor oral (n = 14) immunotherapy with birch pollen allergen preparations made the food sensitivity decrease significantly more than the placebo oral immunotherapy (n = 16).
↩[3] - Herrmann D, Henzgen M, Frank E, Rudeschko O, Jäger L. Effect of hyposensitization for tree pollinosis on associated apple allergy. J Investig Allergol Clin Immunol 1995;5:259-267
Twenty patients suffering from birch pollen allergy received two or three courses of immunotherapy in successive years. In 9 patients, the fruit allergy improved; 4 patients reported no improvement. In 3 patients, the fruit allergy developed after beginning the immunotherapy. At the end of the 3 years, 16 of these patients were allergic to fruit, 13 of them to apple. After each preseasonal course of immunotherapy with tree pollen extract, a temporal and parallel increase in the titers of IgE antibodies to birch pollen allergens and apple allergens were observed. In contrast, only the titers of birch pollen allergen specific IgG and IgG4 increased, whereas apple allergen specific IgG and IgG4 did not, or only very slightly. In Western blot studies, IgG4 antibodies bound to more components of apple extract than birch pollen extract. On the average, IgG4 antibodies recognize more components of apple and birch pollen extracts than do IgE antibodies. In histamine release studies, the sensitivity of washed leukocytes to birch pollen extract decreased significantly during the observation time. However, the difference between apple extract-induced histamine release before and after immunotherapy was not significant. None of the immunological parameters investigated here correlate well with severity or prognosis of the fruit (apple) allergy. The clinical improvement of pollinosis was associated with a rise in birch pollen specific IgG4 antibody titers and a decrease of allergen-induced histamine liberation. Beside improvement of the fruit allergy in 56% of the cases, the courses of apple specific IgE and IgG4 antibody titers seem to indicate a slight sensitization against apple allergens.
↩[4] - Asero R. Effects of birch pollen-specific immunotherapy on apple allergy in birch pollen-hypersensitive patients. Clin Exp Allergy 1998;28:1368-1373
Background: Most patients with birch pollen allergy report oral allergy symptoms after eating fresh apples and other vegetable foods. Major birch pollen and apple allergens, Bet v 1 and Mal d 1, are highly homologous; as a consequence, pollen-specific immunotherapy (SIT) might be expected to improve apple hypersensitivity.
OBJECTIVE: To evaluate the clinical and immunological effects of birch pollen SIT on oral allergy syndrome (OAS) induced by apples.
METHODS: A prospective study carried out in 49 birch pollen-sensitive patients with apple-induced OAS who received injection immunotherapy for 12, 24, or 36 months. Twenty-six patients not submitted to SIT and followed up for 12-48 months were used as controls. Both SPT and open oral challenges with fresh golden delicious apple were performed, as well as specific IgE measurements, before and after SIT.
RESULTS: Forty-one patients (84%) vs no control (0%) reported a significant reduction (50-95%) or a total disappearance (100%) of OAS symptoms after SIT (P < 0.001). Similar responses were observed in patients treated for 12, 24, or 36 months. SIT also induced a marked reduction in skin reactivity against fresh apple in 43 patients (88%). The effect of SIT was inversely related with baseline skin reactivity: 50% and 8% patients with a weakly or strongly positive baseline apple skin prick tests (SPT), respectively, did not report changes in OAS severity after SIT (P < 0.01). In contrast, baseline birch pollen-specific or apple-specific IgE antibodies levels did not influence SIT effectiveness on OAS. SIT induced a marked decrease in birch pollen-specific IgE levels (P < 0.001), whereas apple-specific IgE showed an unexpected variability (reduction in 21%, no change in 43%, increase in 38%). No control subject reported a reduction in OAS severity or showed a decrease in skin reactivity at follow-up (P < 0.001).
CONCLUSIONS: SIT with birch pollen extracts effectively reduces clinical apple sensitivity and skin reactivity in most cases after only 1 year of treatment; these effects are not paralleled by a similar reduction in apple-specific IgE. These findings suggest a decrease in activability of effector cells as the mechanism underlying clinical benefit
↩[5] - Bolhaar STHP, Tiemessen MM, Zuidmeer L, van Leeuwen A, Hoffmann-Sommergruber K, Bruijnzeel-Koomen CAFM, et al. Efficacy of birch-pollen immunotherapy on cross-reactive food allergy confirmed by skin tests and double-blind food challenges. Clin Exp Allergy 2004;34:761-769
BACKGROUND: The effect of birch-pollen immunotherapy (IT) on cross-reactive food allergies is controversial .
OBJECTIVE: The aim of this study was to investigate the effect of birch-pollen IT on apple allergy and to evaluate recombinant allergens and double-blind placebo-controlled food challenges (DBPCFCs) as monitoring tools .
METHODS: Twenty-five adult birch-pollen- and apple-allergic patients were randomly divided into two groups, either receiving birch-pollen IT or symptomatic drugs only. IgE and IgG4 antibodies against birch pollen, apple, natural Bet v 1 and Mal d 1 were measured. In addition, skin prick tests (SPT) were performed using recombinant Bet v 1 (rBet v 1) and Mal d 1 (rMal d 1). Clinical outcome was evaluated by DBPCFC. CD4(+)CD25(+) regulatory T cells (Tregs) were isolated from peripheral blood and tested in functional assays .
RESULTS: Birch-pollen IT resulted in a significant decrease of SPT reactivity for rBet v 1 (30-fold) and rMal d 1 (10-fold) already after 3 months. IgG4 antibodies were potently induced against Bet v 1, displaying cross-reactivity to Mal d 1. Visual analogue scale scores decreased >10-fold in 9/13 patients of the IT group, with three patients converting to negative. In the control group, no decrease was observed. Birch-pollen IT did not lead to detectable changes in the number or function of the CD4(+)CD25(+) Tregs .
CONCLUSIONS: This trial supports the claims that birch-pollen IT also decreases allergy to foods containing Bet v 1-homologous allergens. Recombinant allergens and DBPCFCs have proven to be useful tools for monitoring the effect of birch-pollen IT on linked food allergies.
↩[6] - Skamstrup Hansen K, Sondergaard Khinchi M, Stahl Skov P, Bindslev-Jensen C, Poulsen LK, Malling HJ. Food allergy to apple and specific immunotherapy with birch pollen. Mol Nutr Food Res 2004;48:441-448
Conflicting results concerning the effect of specific pollen immunotherapy (SIT) on allergy to plant foods have been reported. The aim of this study was to investigate the effect of SIT using a birch pollen extract on food allergy with focus on allergy to apple. Seventy-four birch pollen-allergic patients were included in a double-blind, double-dummy, and placebo-controlled comparison of sublingual-swallow (SLIT) and subcutaneous (SCIT) administration of a birch pollen extract. Sixty-nine percent of these patients reported allergy to apple. The clinical reactivity to apple was evaluated by open oral challenges with fresh apple and a questionnaire. The immunoglobulin E (IgE)-reactivity was assessed by skin prick test (SPT), specific IgE, and leukocyte histamine release (HR). Forty patients were included in the final evaluation of the effect of SIT. The challenges were positive in 9 (SCIT), 6 (SLIT), and 8 (placebo) patients after treatment compared to 10, 4, and 10 patients, respectively, before SIT. The symptom scores to apple during challenges decreased in all groups, but only significantly in the placebo group (p = 0.03). As evaluated by the questionnaire, the severity of food allergy in general did not change and there were no differences between the groups. In spite of a significant effect on seasonal hay fever symptoms and use of medication and decrease in IgE-reactivity, SIT was not accompanied by a significant decrease in the severity of allergy to apple compared to placebo. Therefore, oral allergy syndrome (OAS) to apple should not be considered as a main criterion for selecting patients for birch pollen
↩[7] - Bucher X, Pichler WJ, Dahinden CA, Helbling A. Effect of tree pollen specific, subcutaneous immunotherapy on the oral allergy syndrome to apple and hazelnut. Allergy 2004;59:1272-1276
BACKGROUND: The efficacy of specific immunotherapy (SIT) in pollen allergy is well established. However, its effect on pollen associated food allergy particularly the oral allergy syndrome (OAS) is not definitely ascertained .
OBJECTIVE: The purpose of this controlled prospective study was to investigate whether SIT with tree pollen, mainly birch, has an effect on OAS induced by apple or hazelnut in birch pollen-allergic individuals .
METHODS: Twenty-seven birch pollen-allergic subjects with OAS induced by apple or hazelnut underwent open oral provocation tests (OPT) with increasing doses (1 to 128 g) of fresh apple or ground hazelnut 1 year apart. Fifteen of 27 subjects were treated with SIT and 12 were not. Skin-prick test with birch pollen, apple and hazelnut, and specific serum IgE, IgG and IgG4 to rBet v 1, apple and hazelnut were determined .
RESULTS: Thirteen of 15 (87%) SIT-treated subjects could eat significantly (P <0.001) more of apple or hazelnut without any symptoms/signs. The average tolerated quantity increased from 12.6 to 32.6 g apple after 1 year in this group. In contrast, only one of 12 (8%) individuals without SIT was able to consume a higher amount without symptoms. On evaluating laboratory parameters, only IgG4 antibodies to rBet v 1 were found to be significantly (P <0.01) increased in the SIT-treated group after 1 year .
CONCLUSIONS: The study shows that SIT with extracts containing birch pollen has a positive impact on OAS to apple or hazelnut in birch pollen-allergic individuals. In spite of this outcome, the amount of apple/hazelnut tolerated is still small. Thus, the effect of SIT on the patients' management of OAS remains limited.
↩[8] - Kinaciyan T, Jahn-Schmid B, Radakovics A, Zwölfer B, Schreiber C, Francis JN, et al. Successful sublingual immunotherapy with birch pollen has limited effects on concomitant food allergy to apple and the immune response to the Bet v 1 homolog Mal d 1. J Allergy Clin Immunol 2007;119:937-943
BACKGROUND: Cross-reactivity between the major birch pollen allergen, Bet v 1, and the apple protein, Mal d 1, frequently causes food allergy .
OBJECTIVE: To investigate the effects of successful sublingual immunotherapy (SLIT) with birch pollen extract on apple allergy and the immune response to Bet v 1 and Mal d 1 .
METHODS: Before and after 1 year of SLIT, Bet v 1-sensitized patients with oral allergy syndrome to apple underwent nasal challenges with birch pollen and double-blind placebo-controlled food challenges with apple. Bet v 1-specific and Mal d 1-specific serum antibody levels and proliferation in PBMCs and allergen-specific T-cell lines (TCLs) were determined. Bet v 1-specific TCLs were mapped for T-cell epitopes .
RESULTS: In 9 patients with improved nasal provocation scores to birch pollen, apple-induced oral allergy syndrome was not significantly reduced. Bet v 1-specific IgE and IgG(4) levels significantly increased. Bet v 1-specific T-cell responses to all epitopes and those cross-reactive with Mal d 1 significantly decreased. However, neither Mal d 1-specific IgE and IgG(4) levels nor Mal d 1-induced T-cell proliferation changed significantly. In contrast, Mal d 1-specific TCLs showed increased responses to Mal d 1 after 1 year of SLIT .
CONCLUSION: This longitudinal study indicates that pollen SLIT does not efficiently alter the immune response to pollen-related food allergens, which may explain why pollen-associated food allergy is frequently not ameliorated by pollen immunotherapy even if respiratory symptoms significantly improve. CLINICAL IMPLICATIONS: SLIT with birch pollen may have no clinical effect on associated apple allergy.
↩[9] - Niederberger V, Reisinger J, Valent P, Krauth MT, Pauli G, van Hage M, et al. Vaccination with genetically modified birch pollen allergens: Immune and clinical effects on oral allergy syndrome. J Allergy Clin Immunol 2007;119:1013-1016 ↩
[10] - Skamstrup Hansen K, Sondergaard Khinchi M, Stahl Skov P, Bindslev-Jensen C, Poulsen LK, Malling HJ. Food allergy to apple and specific immunotherapy with birch pollen. Mol Nutr Food Res 2004;48:441-448
Conflicting results concerning the effect of specific pollen immunotherapy (SIT) on allergy to plant foods have been reported. The aim of this study was to investigate the effect of SIT using a birch pollen extract on food allergy with focus on allergy to apple. Seventy-four birch pollen-allergic patients were included in a double-blind, double-dummy, and placebo-controlled comparison of sublingual-swallow (SLIT) and subcutaneous (SCIT) administration of a birch pollen extract. Sixty-nine percent of these patients reported allergy to apple. The clinical reactivity to apple was evaluated by open oral challenges with fresh apple and a questionnaire. The immunoglobulin E (IgE)-reactivity was assessed by skin prick test (SPT), specific IgE, and leukocyte histamine release (HR). Forty patients were included in the final evaluation of the effect of SIT. The challenges were positive in 9 (SCIT), 6 (SLIT), and 8 (placebo) patients after treatment compared to 10, 4, and 10 patients, respectively, before SIT. The symptom scores to apple during challenges decreased in all groups, but only significantly in the placebo group (p = 0.03). As evaluated by the questionnaire, the severity of food allergy in general did not change and there were no differences between the groups. In spite of a significant effect on seasonal hay fever symptoms and use of medication and decrease in IgE-reactivity, SIT was not accompanied by a significant decrease in the severity of allergy to apple compared to placebo. Therefore, oral allergy syndrome (OAS) to apple should not be considered as a main criterion for selecting patients for birch pollen
↩[11] - Kinaciyan T, Jahn-Schmid B, Radakovics A, Zwölfer B, Schreiber C, Francis JN, et al. Successful sublingual immunotherapy with birch pollen has limited effects on concomitant food allergy to apple and the immune response to the Bet v 1 homolog Mal d 1. J Allergy Clin Immunol 2007;119:937-943
BACKGROUND: Cross-reactivity between the major birch pollen allergen, Bet v 1, and the apple protein, Mal d 1, frequently causes food allergy .
OBJECTIVE: To investigate the effects of successful sublingual immunotherapy (SLIT) with birch pollen extract on apple allergy and the immune response to Bet v 1 and Mal d 1 .
METHODS: Before and after 1 year of SLIT, Bet v 1-sensitized patients with oral allergy syndrome to apple underwent nasal challenges with birch pollen and double-blind placebo-controlled food challenges with apple. Bet v 1-specific and Mal d 1-specific serum antibody levels and proliferation in PBMCs and allergen-specific T-cell lines (TCLs) were determined. Bet v 1-specific TCLs were mapped for T-cell epitopes .
RESULTS: In 9 patients with improved nasal provocation scores to birch pollen, apple-induced oral allergy syndrome was not significantly reduced. Bet v 1-specific IgE and IgG(4) levels significantly increased. Bet v 1-specific T-cell responses to all epitopes and those cross-reactive with Mal d 1 significantly decreased. However, neither Mal d 1-specific IgE and IgG(4) levels nor Mal d 1-induced T-cell proliferation changed significantly. In contrast, Mal d 1-specific TCLs showed increased responses to Mal d 1 after 1 year of SLIT .
CONCLUSION: This longitudinal study indicates that pollen SLIT does not efficiently alter the immune response to pollen-related food allergens, which may explain why pollen-associated food allergy is frequently not ameliorated by pollen immunotherapy even if respiratory symptoms significantly improve. CLINICAL IMPLICATIONS: SLIT with birch pollen may have no clinical effect on associated apple allergy.
↩[12] - Möller C. Effect of pollen immunotherapy on food hypersensitivity in children with birch pollinosis. Ann Allergy 1989;62:343-345
Of 72 children with severe rhinoconjunctivitis due to birch pollinosis, 67 (93%) reported sensitivity against nuts, apples, etc. The hayfever symptoms improved by immunotherapy but neither subcutaneous (n = 42) nor oral (n = 14) immunotherapy with birch pollen allergen preparations made the food sensitivity decrease significantly more than the placebo oral immunotherapy (n = 16).
↩[13] - Bucher X, Pichler WJ, Dahinden CA, Helbling A. Effect of tree pollen specific, subcutaneous immunotherapy on the oral allergy syndrome to apple and hazelnut. Allergy 2004;59:1272-1276
BACKGROUND: The efficacy of specific immunotherapy (SIT) in pollen allergy is well established. However, its effect on pollen associated food allergy particularly the oral allergy syndrome (OAS) is not definitely ascertained .
OBJECTIVE: The purpose of this controlled prospective study was to investigate whether SIT with tree pollen, mainly birch, has an effect on OAS induced by apple or hazelnut in birch pollen-allergic individuals .
METHODS: Twenty-seven birch pollen-allergic subjects with OAS induced by apple or hazelnut underwent open oral provocation tests (OPT) with increasing doses (1 to 128 g) of fresh apple or ground hazelnut 1 year apart. Fifteen of 27 subjects were treated with SIT and 12 were not. Skin-prick test with birch pollen, apple and hazelnut, and specific serum IgE, IgG and IgG4 to rBet v 1, apple and hazelnut were determined .
RESULTS: Thirteen of 15 (87%) SIT-treated subjects could eat significantly (P <0.001) more of apple or hazelnut without any symptoms/signs. The average tolerated quantity increased from 12.6 to 32.6 g apple after 1 year in this group. In contrast, only one of 12 (8%) individuals without SIT was able to consume a higher amount without symptoms. On evaluating laboratory parameters, only IgG4 antibodies to rBet v 1 were found to be significantly (P <0.01) increased in the SIT-treated group after 1 year .
CONCLUSIONS: The study shows that SIT with extracts containing birch pollen has a positive impact on OAS to apple or hazelnut in birch pollen-allergic individuals. In spite of this outcome, the amount of apple/hazelnut tolerated is still small. Thus, the effect of SIT on the patients' management of OAS remains limited.
↩[14] - Asero R. Effects of birch pollen-specific immunotherapy on apple allergy in birch pollen-hypersensitive patients. Clin Exp Allergy 1998;28:1368-1373
Background: Most patients with birch pollen allergy report oral allergy symptoms after eating fresh apples and other vegetable foods. Major birch pollen and apple allergens, Bet v 1 and Mal d 1, are highly homologous; as a consequence, pollen-specific immunotherapy (SIT) might be expected to improve apple hypersensitivity.
OBJECTIVE: To evaluate the clinical and immunological effects of birch pollen SIT on oral allergy syndrome (OAS) induced by apples.
METHODS: A prospective study carried out in 49 birch pollen-sensitive patients with apple-induced OAS who received injection immunotherapy for 12, 24, or 36 months. Twenty-six patients not submitted to SIT and followed up for 12-48 months were used as controls. Both SPT and open oral challenges with fresh golden delicious apple were performed, as well as specific IgE measurements, before and after SIT.
RESULTS: Forty-one patients (84%) vs no control (0%) reported a significant reduction (50-95%) or a total disappearance (100%) of OAS symptoms after SIT (P < 0.001). Similar responses were observed in patients treated for 12, 24, or 36 months. SIT also induced a marked reduction in skin reactivity against fresh apple in 43 patients (88%). The effect of SIT was inversely related with baseline skin reactivity: 50% and 8% patients with a weakly or strongly positive baseline apple skin prick tests (SPT), respectively, did not report changes in OAS severity after SIT (P < 0.01). In contrast, baseline birch pollen-specific or apple-specific IgE antibodies levels did not influence SIT effectiveness on OAS. SIT induced a marked decrease in birch pollen-specific IgE levels (P < 0.001), whereas apple-specific IgE showed an unexpected variability (reduction in 21%, no change in 43%, increase in 38%). No control subject reported a reduction in OAS severity or showed a decrease in skin reactivity at follow-up (P < 0.001).
CONCLUSIONS: SIT with birch pollen extracts effectively reduces clinical apple sensitivity and skin reactivity in most cases after only 1 year of treatment; these effects are not paralleled by a similar reduction in apple-specific IgE. These findings suggest a decrease in activability of effector cells as the mechanism underlying clinical benefit
↩[15] - Asero R. How long does the effect of birch pollen injection SIT on apple allergy last ? Allergy 2003;58:435-438
BACKGROUND: Recent studies showed that injection specific immunotherapy (SIT) with birch pollen extract greatly reduces or cures the associated apple allergy in a large proportion of birch pollen-allergic patients. However, the long-term efficacy of SIT for apple allergy has not been assessed .
OBJECTIVE: To evaluate the duration of the effect of injection SIT with birch pollen extract on apple allergy in birch pollen-allergic patients .
METHODS: Thirty birch pollen-allergic patients showing both the clinical disappearance of apple allergy and a negative SPT with fresh apple at the end of their injection SIT course were followed-up at 12-month intervals from 6 months after SIT was stopped. Apple tolerance as well as SPT was assessed on all occasions. Fifty-seven birch pollen-allergic subjects without apple allergy and not submitted to SIT regularly followed-up for the onset of oral allergy syndrome (OAS) were used as controls .
RESULTS: The overall prevalence of OAS after 30 months of follow-up did not differ between patients and controls. Although most patients became re-sensitized to apple by SPT over time, >50% of them were still able to tolerate eating the fruit at the 30-month follow-up visit .
CONCLUSION: Although most patients show a 'natural', gradual propensity to apple re-sensitization (a consequence of prolonged and repeated inhalation of birch pollen responsible for primary sensitization?), the clinical effects of injection SIT on food allergy seem rather long lasting.
↩[16] - Mempel M, Rakosi J, Ring J, Ollert M. Severe anaphylaxis to kiwi fruit: Immunologic changes related to successful sublingual allergen immunotherapy. J Allergy Clin Immunol 2003;111:1406-1409
ABSTRACT: BACKGROUND: CD4+ T-cell epitope immunodominance is not adequately explained by peptide selectivity in class II major histocompatibility proteins, but it has been correlated with adjacent segments of conformational flexibility in several antigens .
METHODS: The published T-cell responses to two venom allergens and two aeroallergens were used to construct profiles of epitope dominance, which were correlated with the distribution of conformational flexibility, as measured by crystallographic B factors, solvent-accessible surface, COREX residue stability, and sequence entropy .
RESULTS: Epitopes associated with allergy tended to be excluded from and lie adjacent to flexible segments of the allergen .
CONCLUSION: During the initiation of allergy, the N- and/or C-terminal ends of proteolytic processing intermediates were preferentially loaded into antigen presenting proteins for the priming of CD4+ T cells.
↩[17] - Kerzla R, Simonowa A, Ring J, Ollert M, Mempel M. Life-threatening anaphylaxis to kiwi fruit: Protective sublingual allergen immunotherapy effect persists even after discontinuation. J Allergy Clin Immunol 2007;119:507-508 ↩
[18] - Mempel M, Rakosi J, Ring J, Ollert M. Severe anaphylaxis to kiwi fruit: Immunologic changes related to successful sublingual allergen immunotherapy. J Allergy Clin Immunol 2003;111:1406-1409
ABSTRACT: BACKGROUND: CD4+ T-cell epitope immunodominance is not adequately explained by peptide selectivity in class II major histocompatibility proteins, but it has been correlated with adjacent segments of conformational flexibility in several antigens .
METHODS: The published T-cell responses to two venom allergens and two aeroallergens were used to construct profiles of epitope dominance, which were correlated with the distribution of conformational flexibility, as measured by crystallographic B factors, solvent-accessible surface, COREX residue stability, and sequence entropy .
RESULTS: Epitopes associated with allergy tended to be excluded from and lie adjacent to flexible segments of the allergen .
CONCLUSION: During the initiation of allergy, the N- and/or C-terminal ends of proteolytic processing intermediates were preferentially loaded into antigen presenting proteins for the priming of CD4+ T cells.
↩[19] - Pauli G, Bessot JC, Dietemann-Molard A, Braun PA, Thierry R. Celery sensitivity: clinical and immunological correlations with pollen allergy. Clin Allergy 1985;15:273-279
The authors studied twenty patients with celery allergy and concomitant hypersensitivity to certain pollens (mugwort, birch). The specific symptoms induced by eating celery were attacks of urticaria and angio oedema (seventeen out of twenty) respiratory complaints (eight out of twenty), systemic anaphylaxis with vascular collapse (three out of twenty). A strong association between clinical reactions to celery and mugwort sensitization, and to a lesser degree between celery allergy and birch pollen sensitization was established. Celery allergy is mediated by IgE antibodies and can be easily diagnosed by cutaneous tests using fresh material and/or by adequate RAST test. RAST inhibitions performed on individual sera suggest the existence of common antigens in celery and mugwort, and in celery and birch pollen. However, the exact nature of these common antigens has not yet been determined.
↩[20] - Fox AT, Lack G. High Environmental Exposure to Peanut in Infancy as a Risk Factor for Peanut Allergy. J Allergy Clin Immunol 2005;115(2 suppl.):S34
RATIONALE: Over 90% of peanut allergic children react on their first known exposure. The route by which sensitisation has occurred is unclear Recent data demonstrates suggests low dose cutaneous exposure as a likely route of sensitization
METHODS: Retrospective, case controlled study investigating the role of infant‚s environmental peanut exposure on later allergy. Dietary questionnaires were completed before subjects were aware of allergic status, to avoid recall bias. Questionnaires asked about maternal peanut consumption during pregnancy, breast feeding and the rest of the child‚s first year of life. Similarly, information was obtained about peanut consumption amongst all other household members to enable quantification of overall exposure to peanut in the child‚s household. Exposure was compared in 3 groups of age matched children: children with peanut allergy, children with egg allergy (but not peanut sensitised) and non-allergic children
RESULTS: Average weekly household peanut consumption in the peanut allergic cases (n=43) was 111g as compared to 65g in the normal controls (n=31) and only 31g in the high risk egg allergic controls (n=42). The Kruskall-Wallis test gives a p-value of 0.02, providing sufficient evidence of a difference between the 3 groups
CONCLUSIONS: Data suggest that increased exposure to environmental peanut promotes sensitisation whilst low levels may be protective in atopic children. This supports the hypothesis that peanut sensitization occurs as a result of environmental exposure
↩[21] - Bilo B, Czarnobilska E, Obtulowicz K. Specific immunotherapy and oral allergy syndrome (OAS) in pollen allergy. EAACI 25th Congress, Vienna, 10-14 June, 2006, Poster n°1366
Intolerance of plant-derived foods is an increasing problem in patients with pollen allergy. Aim of this study was to determine the relationship between specific immunotherapy (SIT) with pollen allergens and OAS prevalence. The study population included 57 subjects (31 M, 26 F, mean age 26.5 years) undergoing subcutaneous SIT in the Department of Clinical and Environmental Allergology in Cracow, in whom a detailed information on reactions to plant-derived foods was obtained. Results of skin tests with inhalant and food allergens (Allergopharma) as well as total and specific IgE levels (before SIT) were analysed. The average SIT duration before enrolment was 3 years. In 30 out of 41 subjects with SIT lasting over 1 year, a marked improvement of symptoms was observed. The mean duration of pollinosis symptoms was 10.8 years. In 17 patients OAS symptoms developed (mean duration 6.2 years): in one subject prior to the occurrence of pollinosis, in 12 before SIT was initiated and in 4 during SIT; in 3 subjects OAS symptoms improved during SIT (apple tolerance appeared). The predominant symptoms included itching in the mouth, throat irritation, less frequently lip, palate or tongue oedema; they occurred after the consumption of apple (14 subjects), celery (12), hazelnut (11), less frequently after carrots, peaches or other fruit.. Compared to subjects with a good food tolerance, OAS subjects were characterized by older age (30.6 vs. 23.5 years), longer duration of symptoms (11.6 vs. 10.4 years), higher rate of female gender (59% vs. 40%, NS), more frequent tree pollen allergy (88% vs. 45%, p<0.005), less frequent grass (70% vs. 98%, p<0.005) or weed pollen allergy (41% vs. 53%, NS). OAS symptoms occur most commonly in patients allergic to tree pollen (or to several groups of pollens, including trees). SIT does not appear to increase OAS incidence and it may be associated with a transitional improvement in food tolerance.
↩[22] - Asero R. Fennel, cucumber, and melon allergy successfully treated with pollen-specific injection immunotherapy. Ann Allergy Asthma Immunol 2000;84:460-462
In subjects with both pollinosis and vegetable food allergy, most allergenic epitopes of fruits and vegetables are present in pollen. A recent study showed a marked reduction or a total disappearance of apple-induced oral allergy syndrome in patients receiving injection immunotherapy with birch pollen extracts. OBJECTIVE: To assess whether vegetable food allergy following other kinds of primary pollinosis may be successfully treated with pollen-specific immunotherapy.
METHODS: A 34-year-old woman with long-standing pollinosis and typical oral allergy syndrome (OAS) with the ingestion of both fennel and cucumber and whose OAS was associated with immediate laryngeal edema after the ingestion of melon, was treated with two commercial depot aluminum hydroxide-adsorbed extracts of 1 grass pollen and 2 mugwort pollen 50% + ragweed pollen 50%.
RESULTS: After 36 months of injection specific immunotherapy, the patient was able to tolerate both fresh fennel and cucumber without consequence on open oral challenge tests. After 43 months of immunotherapy, the patient tolerated fresh melon as well on open oral challenge. She has re-introduced these vegetables in her normal diet. Skin tests showed no reactivity to fresh fennel and there was a reduction of the wheal induced by fresh cucumber. CONCLUSION: Vegetable food allergy following primary sensitization to pollens, other than birch, may also be effectively reduced by pollen-specific injection immunotherapy.
↩[23] - Kelso JM, Jones RT, Tellez R, Yunginger JW. Oral allergy syndrome successfully treated with pollen immunotherapy. Ann Allergy Asthma Immunol 1995;74:391-396
BACKGROUND: Some patients with allergic rhinitis have oral allergic reactions to fresh fruits and vegetables. This phenomenon has been termed "oral allergy syndrome" and is proposed to be due to cross-reacting allergens in the foods and pollens.
METHODS: We report a patient with allergic rhinitis and oral allergy syndrome treated with pollen immunotherapy. Prior to immunotherapy, eating any fresh fruit or vegetable caused immediate itching and swelling of his tongue and throat. Prick skin test titration with pollens and foods was performed before and after 13 months of immunotherapy. Specific IgE immunoassay was performed with the same extracts on serum obtained before and after 7 and 13 months of immunotherapy. IgE immunoblots were performed on the same extracts separated by polyacrylamide gel electrophoresis using sera from the same time periods.
RESULTS: After 1 year on immunotherapy, the patient's allergic rhinitis symptoms resolved, and he was able to eat fresh fruits and vegetables without reaction. Skin testing and specific IgE immunoassay demonstrated a marked reduction in sensitivity to not only the pollens but the foods as well. Immunoblots revealed that the intensity of IgE binding to most components of the extracts, some common to pollens and foods, declined during immunotherapy.
CONCLUSIONS: These results support the notion that oral allergy syndrome is due to cross-reacting allergens in foods and pollens and may be amenable to treatment with pollen immunotherapy
↩[24] - Baumann K, Roessler F, Mullner G, Pichler WJ, Helbling A. Effect of the specific, subcutaneous immunotherapy with pollen extracts on the pollen-associated food allergy. A retrospective analysis on 72 patients. Allergologie 2002;25:326-332
Whereas the efficacy of the specific immunotherapy (SIT) in pollen allergy has been established, its consequence on the pollen-associated food allergy particularly the oral allergy syndrome (OAS) is less clear. In a retrospective study, we investigated the effect of SIT with pollen extracts in pollen-allergic subjects on the OAS. In addition, we looked for factors that could be prognostic for the change of OAS. 72 subjects (39 male, 33 female with a mean age of 32 years) allergic to pollen with a concomitant pollen-associated food allergy, namely OAS, who have been treated for an average of 2,0 years by SIT were interviewed using a standardized questionnaire. For control served 40 individuals (17 male, 23 female; mean age 29 years) allergic to pollen and a pollen-associated food allergy (OAS) without SIT. 38 of 72 subjects (53%) treated with SIT had an improvement of their OAS. However, 23 (32%) claimed an unchangeable and 11 (15%) even an increase of the OAS. Of the controls, an improvement was realized in only 3 individuals (8%). 20 of them (50%) declared no change and 17 a worsening of the OAS. In conclusion, our results suggest that pollen-associated food allergy, specifically the OAS, can be reduced in more than half of the patients by SIT. On the other hand, in 15% of the SIT-treated collective an expansion of the spectrum of foods inducing symptoms was experienced. A successful development of the OAS by SIT seems to occur if patients are older than 20 years of age, have a clinical relevant birch pollen allergy and suffer from an intensive OAS. Failure regarding OAS seems more likely if SIT with birch pollen is combined with grass pollen extracts.
↩[25] - Bilo B, Czarnobilska E, Obtulowicz K. Specific immunotherapy and oral allergy syndrome (OAS) in pollen allergy. EAACI 25th Congress, Vienna, 10-14 June, 2006, Poster n°1366
Intolerance of plant-derived foods is an increasing problem in patients with pollen allergy. Aim of this study was to determine the relationship between specific immunotherapy (SIT) with pollen allergens and OAS prevalence. The study population included 57 subjects (31 M, 26 F, mean age 26.5 years) undergoing subcutaneous SIT in the Department of Clinical and Environmental Allergology in Cracow, in whom a detailed information on reactions to plant-derived foods was obtained. Results of skin tests with inhalant and food allergens (Allergopharma) as well as total and specific IgE levels (before SIT) were analysed. The average SIT duration before enrolment was 3 years. In 30 out of 41 subjects with SIT lasting over 1 year, a marked improvement of symptoms was observed. The mean duration of pollinosis symptoms was 10.8 years. In 17 patients OAS symptoms developed (mean duration 6.2 years): in one subject prior to the occurrence of pollinosis, in 12 before SIT was initiated and in 4 during SIT; in 3 subjects OAS symptoms improved during SIT (apple tolerance appeared). The predominant symptoms included itching in the mouth, throat irritation, less frequently lip, palate or tongue oedema; they occurred after the consumption of apple (14 subjects), celery (12), hazelnut (11), less frequently after carrots, peaches or other fruit.. Compared to subjects with a good food tolerance, OAS subjects were characterized by older age (30.6 vs. 23.5 years), longer duration of symptoms (11.6 vs. 10.4 years), higher rate of female gender (59% vs. 40%, NS), more frequent tree pollen allergy (88% vs. 45%, p<0.005), less frequent grass (70% vs. 98%, p<0.005) or weed pollen allergy (41% vs. 53%, NS). OAS symptoms occur most commonly in patients allergic to tree pollen (or to several groups of pollens, including trees). SIT does not appear to increase OAS incidence and it may be associated with a transitional improvement in food tolerance.
↩[26] - Asero R. Pollen specific immunotherapy is not a risk factor for de novo sensitization to cross-reacting allergens in monosensitized subjects. J Investig Allergol Clin Immunol 2006;16:253-257
BACKGROUND: Some studies have suggested that specific immunotherapy (SIT) may cause de novo sensitization to allergenic proteins to which patients were not previously allergic. This event might theoretically involve cross-reacting pollen allergens, such as profilin or polcalcins, posing a risk of SIT-induced polysensitization to pollens in patients who were originally monosensitized.
OBJECTIVES: The aim of this study was to assess whether injection SIT with commercial pollen extract represents a risk factor for the de novo development of sensitization to different pollens in monosensitized patients.
METHODS: The study involved 142 subjects diagnosed as being monosensitized to a single pollen: 64 patients who were administered a 3-year course of injection SIT and 78 controls. Subjects underwent control skin prick tests (SPT) with a series of 8 seasonal airborne allergens at least 3 years after the first visit. Patients with 5 or more new sensitivities on SPT were considered to be de novo polysensitized.
RESULTS: At the end of the 3-year follow-up period, the proportion of polysensitized subjects was identical in previously monosensitized patients who underwent SIT and control individuals (11% and 10%, respectively). Individuals who were polysensitized were significantly younger than those who were not (mean age +/- SD, 21.6 +/- 11.0 years vs. 31.6 +/- 15.6 years; P < .05).
CONCLUSION: SIT does not represent a risk factor for progression towards multiple pollen sensitization in monosensitized pollen-allergic patients.
↩[27] - Nowak-Wegrzyn AH, Mofidi S, Ma S, Bardina L, Beyer K. Birch and Ragweed Pollen Immunotherapy in the Treatment of Pollen-Food Allergy Syndrome. AAAAI 60th Annual Meeting, San Francisco, 19-23 March 2004, Poster n°483
Rationale Fruit/vegetable allergy affects up to 50% of pollen-allergic adults. Pollen sensitization is regarded as the primary event with subsequent development of allergy to cross-reactive fruits and vegetables. We sought to determine the effect of pollen immunotherapy on pollen-food allergy syndrome. Methods A randomized open trial of birch and ragweed pollen immunotherapy in patients with birch and ragweed allergic rhinitis and oral allergy to apple and/or cantaloupe Results Sixteen birch and ragweed allergic patients, median age 30 years (range; 11-47) with apple and/or cantaloupe allergy confirmed by double-blinded placebo-controlled oral challenge were randomized to receive birch and ragweed pollen immunotherapy (n=9) or to a control group that did not receive immunotherapy (n=7). Four immunotherapy patients underwent oral challenges at median 15 months (range; 12-16) and 5 control patients were challenged at median 12 months (range; 12-18). Following immunotherapy, blinded challenges revealed decreased symptom scores, mean 4.8 versus 1.0 (p<0.04). Open challenge symptom scores were also lower, median 3.0 vs 1.5 (p=0.3) and patients tolerated larger amount of an open challenge, median 16% vs 68% (p=0.03). Such significant changes were not seen in the control patients who at follow-up had not significantly different symptom scores on blinded challenge, median 4 versus 3 (p=0.06) and on open challenge, median 5.4 vs 4.6 (p=0.6). Control patients tolerated 100% of an open challenge at baseline and at follow-up. Conclusion Birch and ragweed pollen immunotherapy increases tolerance to fruits in subjects with pollen-food allergy syndrome.
↩[28] - Alonso R, Enrique E, Pineda F, Basagaña M, San Miguel-Moncín MM, Bartra J, et al. An Observational Study on Outgrowing Food Allergy during Non-Birch Pollen-Specific, Subcutaneous Immunotherapy. Int Arch Allergy Immunol 2007;143:185-189
BACKGROUND: Birch pollen-specific immunotherapy (SIT) decreases allergy to foods containing birch pollen-homologous allergens. Cross-reactivity was also observed between plane tree pollen and some vegetable foods .
OBJECTIVE: The aim of this study was to evaluate the outgrowing of food allergy by patients suffering from vegetable food allergy associated with plane tree pollinosis (rhinoconjunctivitis and/or asthma) during plane tree pollen SIT .
METHODS: An observational and prospective study was conducted in 16 adult patients suffering from vegetable food allergy (hazelnut, walnut, lettuce, peach and cherry) and from plane tree pollinosis receiving plane tree pollen SIT for 1 year. Open oral challenges with the implicated food were performed before and after SIT. Blood samples were drawn for measurement of pollen- and food-specific IgE and IgG4 before and after treatment .
RESULTS: Plane tree SIT resulted in a significant decrease in food allergy, since the mean food quantity provoking objective symptoms increased from 2.19 to 13.74 g (p < 0.05), and 6 of the 11 patients tolerated the highest level (25 g) of the challenged food after plane tree SIT. Laboratory data also showed a decrease in IgE levels and an increase in IgG4 levels after immunotherapy .
CONCLUSION: SIT with plane tree pollen has a positive impact on food allergy in plane tree pollen-allergic subjects.
↩[29] - Ball T, Sperr WR, Valent P, Lidholm J, Spitzauer S, Ebner C, et al. Induction of antibody responses to new B cell epitopes indicates vaccination character of allergen immunotherapy. Eur J Immunol 1999;29:2026-2036
Whether the modulation of antibody responses can contribute to the improvement of clinical symptoms in patients receiving allergen immunotherapy represents a controversial issue. We have used purified [seven recombinant (r) and one natural] timothy grass pollen allergens as well as recombinant B cell epitope-containing fragments of the major timothy grass pollen allergen, Phl p 1, to investigate humoral immune responses in eight allergic patients receiving grass pollen-specific immunotherapy. We found that the administration of aluminium hydroxide-adsorbed grass pollen extract induced complex changes in allergen/epitope-specific antibody responses: increases in IgG subclass (IgG1, IgG2, IgG4) responses against allergens recognized before the therapy were observed. All eight patients started to mount IgE and IgG4 responses to continuous Phl p 1 epitopes not recognized before the therapy and a de novo induction of IgE antibodies against new allergens was found in one patient. Evidence for a protective role of IgG antibodies specific for continuous Phl p 1 epitopes was provided by the demonstration that preincubation of rPhl p 1 with human serum containing therapy-induced Phl p 1-specific IgG inhibited rPhl p 1-induced histamine release from basophils of a grass pollen-allergic patient. Our finding that immunotherapy induced antibody responses against previously not recognized B cell epitopes indicates the vaccination character of this treatment. The fact that patients started to mount de novo IgE as well as protective IgG responses against epitopes may explain the unpredictability of specific immunotherapy performed with allergen extracts and emphasizes the need for novel forms of component-resolved immunotherapy.
↩[30] - van Ree R, Van Leeuwen WA, Dieges PH, Van Wijk RG, De Jong N, Brewczyski PZ, et al. Measurement of IgE antibodies against purified grass pollen allergens (Lol p 1, 2, 3 and 5) during immunotherapy. Clin Exp Allergy 1997;27:68-74
BACKGROUND: IgE titres tend to rise early after the start of immunotherapy, followed by a decline to pre-immunotherapy levels or lower.
OBJECTIVES: We were interested to know whether the early increase in IgE antibodies includes new specificities of IgE, and whether these responses persist.
METHODS: Sera of 64 patients undergoing grass pollen immunotherapy were tested for IgE against four purified grass pollen allergens: Lol p 1, 2, 3, and 5. At least two serum samples were taken, one before the start of therapy and one between 5 and 18 months after the first immunization (mean: 10 months).
RESULTS: The mean IgE responses to Lol p 1, 2 and 3 showed a moderate but not significant increase. In contrast, the mean IgE response to Lol p 5 showed a significant decrease of > 30%. IgE against total Lohum perenne pollen extract moderately increased (> 20%), showing that a RAST for total pollen is not always indicative for the development of IgE against its major allergens. For > 40% of the patients it was found that IgE against one or more of the four allergens increased, while IgE against the remaining allergen(s) decreased. For 10 sera the ratio of IgE titres against at least two allergens changed by at least a factor of 5. The changes in specific IgE also included conversions from negative (< 0.1 RU) to positive (0.6 to 5.0 RU) for five patients. For two patients, the induction of these 'new' IgE antibodies against major allergens was shown to result in a response that was persistent over several years.
CONCLUSION: Although active induction of new IgE specificities by immunotherapy was not really proven, the observations in this study indicate that monitoring of IgE against purified (major) allergens is necessary to evaluate changes in specific IgE in a reliable way.
↩[31] - Mari A. Skin test with a timothy grass (Phleum pratense) pollen extract vs. IgE to a timothy extract vs. IgE to rPhl p 1, rPhl p 2, nPhl p 4, rPhl p 5, rPhl p 6, rPhl p 7, rPhl p 11, and rPhl p 12: epidemiological and diagnostic data. Clin Exp Allergy 2003;33:43-51
The diagnostic approach to grass pollen allergy is now possible by detecting specific IgE to its allergenic components.
ObjectiveTo compare the IgE reactivity to a timothy grass pollen extract with the IgE reactivity to eight allergenic components from the same source (Phl p 1, 2, 4, 5, 6, 7, 11, 12). Both were compared with the skin test reactivity to a timothy grass extract.
MethodsA population survey was carried out by means of the skin test to identify grass-allergic subjects, and to characterize them in terms of demographic and allergological parameters. Seven hundred and forty-nine sera were available for IgE detection to a timothy extract, to the recombinant Phl p 1, 2, 5, 6, 7, 11, 12, and to native Phl p 4 and bromelain. Results were stratified by means of demographic and allergy parameters.
ResultsNinety-five per cent of the sera had detectable IgE to the timothy extract. Prevalence of IgE reactivity increased from 86.8% to 93.3% as the number of combined reactive molecules rose from 2 to 8. Adjusted prevalences for each allergen were: rPhl p 1 = 83%, rPhl p 2 = 55%, nPhl p 4 = 70%, rPhl p 5 = 50%, rPhl p 6 = 44%, rPhl p 7 = 7%, rPhl p11 = 43%, rPhl p 12 = 15%. Isolated reactivity to rPhl p 1 was 6%, whereas it was negligible for the remaining molecules. IgE reactivity prevalence and mean values differed when patients were stratified on the basis of their associated pollen reactivity and their skin test reactivity grade. No differences were found when age, symptom type and duration were considered. Up to eight-fold higher IgE concentrations were found when the sum of IgE to molecules was compared with IgE to the extract. Testing for the IgE reactivity to the glycan of the native Phl p 4 allergen showed a possible interference with prevalence and value estimation. Higher prevalence values were found in previously immunotherapy-treated patients.
ConclusionsThe use of a complete panel of grass allergenic molecules can mimic the current use of allergenic extracts, but new relevant information, such as individual pattern of reactivity, adjusted prevalence, correct specific IgE concentration, can be achieved only by means of discrete allergenic molecules.
↩[32] - 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
"BACKGROUND: Allergen immunotherapy is a widely accepted treatment for IgE-mediated allergies. The evaluation of immunotherapy-induced IgG4 antibodies based on allergen extract is questionable because the amount of allergen-extract-specific IgG4 to individual disease-eliciting allergens cannot be determined using crude allergen extracts. In this study, we examined the specific IgE and IgG4 serum binding profiles to individual Phleum pratense allergens in grass-pollen-sensitive patients who had received grass-pollen-specific immunotherapy (SIT) .
METHODS: The study included 33 patients from North-West Italy. All suffered from seasonal rhinoconjunctivitis and/or asthma. A modified ""cluster"" regimen of injections of a standardized aluminium-adsorbed P.pratense extract, with once-weekly visits and 10 injections for 5 weeks followed by 3 weeks of maintenance injections was instituted. Patients' sera were analyzed for specific IgE and IgG4 reactivity to individual P. pratense allergens (recombinant Phl p 1, Phl p 2, Phl p 5, Phl p 6, Phl p 7, Phl p 11, Phl p12 and native Phl p 4) and natural P. pratense extract using the Pharmacia CAP system .
RESULTS: IgE reactivities to new allergen components were not detected by CAP in treated patients after 15 weeks and a cumulative dose of approximately 65 microg of the major allergen Phl p 5. Patients lacking specific IgE reactivity towards individual allergens at the start of SIT did not produce significant levels of specific serum IgG4 to serum IgE-negative allergens. On the other hand, an increase in specific IgG4 only to allergens to which patients were previously sensitized was observed. Significant increases in specific IgG4 levels to rPhl p 1 (p < 0.05), 2 (p < (0.01), 5 (p < 0.0001), 6 (p < 0.0001), 7 (p < 0.05), 11 (p < 0.05) and nPhl p 4 (p < 0.01) were observed after P. pratense extract immunotherapy. No significant rPhl p 12-specific IgG4 antibody increase was documented after treatment .
CONCLUSION: These findings suggest that Phl p 12 was underrepresented in the extract used, as indicated by the low specific IgG4 response induced by this grass-pollen-specific vaccine. Thus, the simple detection of specific serum IgG4 antibodies a few weeks after the start of SIT could represent a valuable tool to estimate the presence of relevant allergens in a given immunotherapeutic allergen extract."
↩[33] - Aberer W, Hawranek T, Reider N, Schuster C, Sturm G, Kränke B. Immunoglobulin E and G antibody profiles to grass pollen allergens during a short course of sublingual immunotherapy. J Investig Allergol Clin Immunol 2007;17:131-136
BACKGROUND: Various studies have shown the clinical efficacy of sublingual immunotherapy in grass pollen-induced rhinoconjunctivitis. However, even short-term treatment with grass extracts might cause sensitizations to formerly unrecognized antigens. OBJECTIVE: To determine whether the antibody profiles are changing in patients receiving a defined grass pollen extract prior to and during the grass pollen season.
METHODS: A randomized, double blind, placebo-controlled, multicenter phase I/I111 trial was started prior to the commencement of the grass pollen season. Patients with grass pollen allergy were randomly allocated to four groups, and received daily a standardized tablet at different doses. Treatment was started 8 weeks prior to the beginning of the pollen season and stopped at the end of the season. Blood samples were taken at the beginning of the study, at the beginning and the end of the pollen season, and one year after commencement of the study.
RESULTS: At the beginning of the study, all patients tested positive for the major grass pollen allergens, but negative to the minor antigens. In all patients, the degree of antibody reactivity rose considerably after starting active treatment and fell back to the initial values within one year. Immunoglobulin (Ig) E antibodies to the minor antigens remained negative, independent of treatment and seasonal exposure. In contrast to IgE, specific IgG antibodies to all allergens tested revealed no specific trend.
CONCLUSIONS: Immunotherapy with grass allergen tablets was accompanied by an increase in grass-specific IgE antibodies, which further increased during pollen exposure, followed by a post-treatment drop in patient- and disease-specific antibodies. During this short course of treatment, no patient developed any additional sensitizations.
↩[34] - Mattsson L, Nordlund M, Vieths S, Härfast B, Lidholm J, Lijla G. Changes in specific IgE, IgG and IgG4 to birch pollen allergens during specific immunotherapy. EAACI 23th Congress, Amsterdam, 12-16 June, 2004, Poster n°488 ↩
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