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 PatientsRossi R.E.a · Monasterolo G.b
aAllergy Unit, National Health Service, Cuneo; bLaboratorio Analisi Chimico-Cliniche e Microbiologia, Ospedale Santissima Trinità, Fossano, Ospedale Santissima Annunziata, Savigliano, Italy
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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 µg 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.
© 2004 S. Karger AG, Basel
Wilson DR, Irani AM, Walker SM, Jacobson MR, Mackay IS, Schwartz LB, et al: Grass pollen immunotherapy inhibits seasonal increases in basophils and eosinophils in the nasal epithelium: Clin Exp Allergy 2001;31:1705–1713.
- Durham SR, Till SJ: Immunological changes associated with allergen immunotherapy. J Allergy Clin Immunol 1998;102:157–164.
Van Ree R, Aalberse RC: Rabbit IgG directed to a synthetic C-terminal peptide of the major grass pollen allergen Lol p 1 inhibits human basophil histamine release induced by natural Lol p 1. Int Arch Allergy Immunol 1995;106:205–257.
- Batard T, Weyer A, Laroze A, et al: Isotypic analysis of grass pollen-specific antibodies in human plasma. Biological activity of allergen-specific and autoanti-IgE antibody fractions of basophil histamine release. Clin Exp Allergy 1996;26:1308–1315.
Djurup R, Malling HJ: High IgG4 antibody level is associated with failure of immunotherapy with inhalant allergens. Clin Allergy 1987;7:459–468.
- McHugh SM, Lavelle B, Kemeny DM, Patel S, Ewan PW: A placebo-controlled trial of immunotherapy with two extracts of Dermatophagoides pteronyssinus in allergic rhinitis, comparing clinical outcome with changes in antigen-specific IgE, IgG, and IgG subclasses. J Allergy Clin Immunol 1990;86:521–531.
- Vrtala S, Ball T, Spitzauer S, Pandjaitan B, Suphioglu C, Knox B, Sperr WR, Valent P, Kraft D, Valenta R: Immunization with purified natural and recombinant allergens induces mouse IgG1 antibodies that recognize similar epitopes as human IgE and inhibit the human IgE-allergen interaction and allergen-induced basophil degranulation. J Immunol 1998;160:6137–6144.
- Van-Neerven R JJ, Wikborg T, Lund G, Jacobs B, Brinch-Nielsen A, Arnved J, Ipsen H: Blocking antibodies induced by specific allergy vaccination prevent the activation of CD4+ T cells by inhibiting serum-IgE-facilitated allergen presentation. J Immunol 1999;163:2944–2952.
- Vrtala S, Akdis CA, Budak F, Akdis M, Blaser K, Kraft D, Valenta R: T cell epitope-containing hypoallergenic recombinant fragments of the major birch pollen allergen, Bet v 1, induce blocking antibodies. J Immunol 2000;165:6653–6659.
- Mothes N, Heinzkill M, Drachenberg KJ, et al: Allergen-specific immunotherapy with a monophosphoryl lipid A-adjuvanted vaccine reduced seasonally boosted IgE production and inhibition of basophil histamine release by therapy-induced blocking antibodies. Clin Exp Allergy 2003;33:1198–1208.
- Gehlhar K, Schlaak M, Becker W-M, Bufe A: Monitoring allergen immunotherapy of pollen allergic patients: The ratio of allergen-specific IgG4 and IgG4 correlates with clinical outcome. Clin Exp Allergy 1999;29:497–506.
- Rossi RE, Monasterolo G, Diana A, Monasterolo S, Delucchi M: Evaluation of two grass pollen extracts for immunotherapy by serum determinations of specific IgE and IgG4 antibodies towards purified timothy grass pollen allergens (Phl p1, 2, 4, 5, 6, 7, 11, 12) in patients undergoing hyposensitization treatment. Allergol Int 2002;51:233–240.
- Klein F. Skavaril F, Vermeeren R, Vlug A, Duimel W J: The quantification of human IgG subclasses in reference preparations. Clin Chim Acta 1985;150:119–127.
- Rossi RE, Monasterolo G, Monasterolo S: Detection of specific IgE antibodies in the sera of patients allergic to birch pollen using recombinant allergens Bet v 1, Bet v 2, Bet v 4:evaluation of different IgE reactivity profiles. Allergy 2003;58:929–932.
- Linhart B, Jahn-Schmid B, Verdino, et al: Combination vaccines for the treatment of grass pollen allergy consisting of genetically engineered hybrid molecules with increased immunogenicity. FASEB J 2002;16:1301–1303. Epub 2002 June 21.
- Kolbe L, Heusser CH, Kolsh E: Isotype-associated recognition of allergen epitopes and its modulation by antigen dose. Immunology 1995;84:285–289.
- Michils A, Mairesse M, Ledent C, Gossart B, Baldassarre S, Duchateau J: Modified antigenic reactivity of anti-phospholipase A2 IgG antibodies in patients allergic to bee venom: Conversion with immunotherapy and relation to sub-class expression. J Allergy Clin Immunol 1998;102:118–126.
- Visco V, Dolocek C, Denepoux S, Le Mao J, Guret C, Rousset F, Guinnepain M T, Kraft D, Valenta R, Weyer A, Banchereau J, Lebecque S: Human IgG monoclonal antibodies that modulate the binding of specific IgE to birch pollen Bet v 1. J Immunol 1996;157:956–962.
- Denepoux S, Eibensterner P, Steinberger P, Vrtala S, Visco V, Weyer D, Banchereau J, Lebeque S: Molecular characterization of human IgG monoclonal antibodies specific for the major birch pollen allergen bet v 1. Anti-allergen IgG can enhance the anaphylactic reaction. FEBS Lett 2000;465:39–46.
- Mahler V, Vrtala S, Kuss O, Diepgen TL, Suck R, Cromwell O, Fiebig H, Hartl A, Thalhamer J, Schuler G, Kraft D, Valenta R: Vaccines for birch pollen allergy based on genetically engineered hypoallergenic derivatives of the major birch pollen allergen, Bet v 1. Clin Exp Allergy 2004;34:115–122.
- Flicker S, Valenta R: Renaissance of the blocking antibody concept in type I allergy. Int Arch Allergy Clin Immunol 2003;132:13–24.
- Valenta R, Ball T, Focke M, Linhart B, Mothes N, Niederberger V, Spitzauer S, Swoboda I, Vrtala S, Westritschnig K, Kraft D: Immunotherapy of allergic disease. Adv Immunol 2004;82:105–153.
- Wacholz PA, Soni NK, Till SJ, Durham SR: Inhibition of allergen-IgE binding to B cells by IgG antibodies after grass pollen immunotherapy. J Allergy Clin Immunol 2003;112:915–922.
- Svenson M, Jacobi HH, Bodtger U, Poulsen LK, Rieneck K, Bendtzen K: Vaccination for birch pollen allergy. Induction of affinity-matured or blocking IgG antibodies does not account for the reduced binding of IgE to Bet v 1. Mol Immunol 2003;39:603–612.
- Hardy CL, Rolland JM, O’Heir RE: Blocking antibody in allergen immunotherapy: The Yin and Yang. Clin Exp Allergy 2004;34:510–512.
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