• 1
    Valovirta E, Passalacqua G, Canonica WG. Non-injection routes for immunotherapy of allergic diseases. Clin Allergy Immunol 2004;18:607623.
  • 2
    Novak N, Haberstok J, Bieber T, Allam JP. The immune privilege of the oral mucosa. Trends Mol Med 2008;14:191198.
  • 3
    Calderon MA, Alves B, Jacobson M, Hurwitz B, Sheikh A, Durham S. Allergen injection immunotherapy for seasonal allergic rhinitis. Cochrane Database Syst Rev 2007;(1):CD001936.
  • 4
    Wilson DR, Lima MT, Durham SR. Sublingual immunotherapy for allergic rhinitis: systematic review and meta-analysis. Allergy 2005;60:412.
  • 5
    Penagos M, Compalati E, Tarantini F, Baena-Cagnani R, Huerta J, Passalacqua G et al. Efficacy of sublingual immunotherapy in the treatment of allergic rhinitis in pediatric patients 3 to 18 years of age: a meta-analysis of randomized, placebo-controlled, double-blind trials. Ann Allergy Asthma Immunol 2006;97:141148.
  • 6
    Horak F, Zieglmayer P, Zieglmayer R, Lemell P, Devillier P, Montagut A et al. Early onset of action of a 5-grass-pollen 300-IR sublingual immunotherapy tablet evaluated in an allergen challenge chamber. J Allergy Clin Immunol 2009;124:471477.
  • 7
    Durham SR, Emminger W, Kapp A, Colombo G, De Monchy JG, Rak S et al. Long-term clinical efficacy in grass pollen-induced rhinoconjunctivitis after treatment with SQ-standardized grass allergy immunotherapy tablet. J Allergy Clin Immunol 2010;125:131138.
  • 8
    Paster BJ, Boches SK, Galvin JL, Ericson RE, Lau CN, Levanos VA et al. Bacterial diversity in human subgingival plaque. J Bacteriol 2001;183:37703783.
  • 9
    Lu FX, Jacobson RS. Oral mucosal immunity and HIV/SIV infection. J Dent Res 2007;86:216226.
  • 10
    Jotwani R, Palucka AK, Al-Quotub M, Nouri-Shirazi M, Kim J, Bell D et al. Mature dendritic cells infiltrate the T cell-rich region of oral mucosa in chronic periodontitis: in situ, in vivo, and in vitro studies. J Immunol 2001;167:46934700.
  • 11
    Allam JP, Duan Y, Winter J, Stojanovski G, Fronhoffs F, Wenghoefer M et al. Tolerogenic T cells, Th1/Th17 cytokines and TLR2/TLR4 expressing dendritic cells predominate the microenvironment within distinct oral mucosal sites. Allergy 2010; 10-9995. [epubmed ahead of print].
  • 12
    Allam JP, Peng WM, Appel T, Wenghoefer M, Niederhagen B, Bieber T et al. Toll-like receptor 4 ligation enforces tolerogenic properties of oral mucosal Langerhans cells. J Allergy Clin Immunol 2008;121:368374.
  • 13
    Rask C, Brimnes J, Lund K. Shorter dosing intervals of sublingual immunotherapy lead to more efficacious treatment in a mouse model of allergic inflammation. Scand J Immunol 2010;71:403412.
  • 14
    Allam JP, Novak N, Fuchs C, Asen S, Berge S, Appel T et al. Characterization of dendritic cells from human oral mucosa: a new Langerhans’ cell type with high constitutive FcepsilonRI expression. J Allergy Clin Immunol 2003;112:141148.
  • 15
    Allam JP, Niederhagen B, Bucheler M, Appel T, Betten H, Bieber T et al. Comparative analysis of nasal and oral mucosa dendritic cells. Allergy 2006;61:166172.
  • 16
    Allam JP, Wurtzen PA, Reinartz M, Winter J, Vrtala S, Chen KW et al. Phl p 5 resorption in human oral mucosa leads to dose-dependent and time-dependent allergen binding by oral mucosal Langerhans cells, attenuates their maturation, and enhances their migratory and TGF-beta1 and IL-10-producing properties. J Allergy Clin Immunol 2010;126:638645.
  • 17
    Didier A, Malling HJ, Worm M, Horak F, Jager S, Montagut A et al. Optimal dose, efficacy, and safety of once-daily sublingual immunotherapy with a 5-grass pollen tablet for seasonal allergic rhinitis. J Allergy Clin Immunol 2007;120:13381345.
  • 18
    Durham SR, Yang WH, Pedersen MR, Johansen N, Rak S. Sublingual immunotherapy with once-daily grass allergen tablets: a randomized controlled trial in seasonal allergic rhinoconjunctivitis. J Allergy Clin Immunol 2006;117:802809.
  • 19
    Larche M. Immune mechanisms of sublingual immunotherapy: are oral Langerhans cells the masters of tolerance? J Allergy Clin Immunol 2010;126:646647.
  • 20
    Allam JP, Stojanovski G, Friedrichs N, Peng W, Bieber T, Wenzel J et al. Distribution of Langerhans cells and mast cells within the human oral mucosa: new application sites of allergens in sublingual immunotherapy? Allergy 2008;63:720727.
  • 21
    Scadding GW, Shamji MH, Jacobson MR, Lee DI, Wilson D, Lima MT et al. Sublingual grass pollen immunotherapy is associated with increases in sublingual Foxp3-expressing cells and elevated allergen-specific immunoglobulin G4, immunoglobulin A and serum inhibitory activity for immunoglobulin E-facilitated allergen binding to B cells. Clin Exp Allergy 2010;40:598606.
  • 22
    Mosges R, Ritter B, Kayoko G, Allekotte S. Carbamylated monomeric allergoids as a therapeutic option for sublingual immunotherapy of dust mite- and grass pollen-induced allergic rhinoconjunctivitis: a systematic review of published trials with a meta-analysis of treatment using Lais tablets. Acta Dermatovenerol Alp Panonica Adriat 2010;19:310.
  • 23
    Nieminen K, Laaksonen K, Savolainen J. Three-year follow-up study of allergen-induced in vitro cytokine and signalling lymphocytic activation molecule mRNA responses in peripheral blood mononuclear cells of allergic rhinitis patients undergoing specific immunotherapy. Int Arch Allergy Immunol 2009;150:370376.
  • 24
    Laaksonen K, Junikka M, Lahesmaa R, Terho EO, Savolainen J. In vitro allergen-induced mRNA expression of signaling lymphocytic activation molecule by PBMC of patients with allergic rhinitis is increased during specific pollen immunotherapy. J Allergy Clin Immunol 2003;112:11711177.
  • 25
    Bohle B, Kinaciyan T, Gerstmayr M, Radakovics A, Jahn-Schmid B, Ebner C. Sublingual immunotherapy induces IL-10-producing T regulatory cells, allergen-specific T-cell tolerance, and immune deviation. J Allergy Clin Immunol 2007;120:707713.
  • 26
    Savolainen J, Nieminen K, Laaksonen K, Laiho T, Jacobsen L, Lahesmaa R et al. Allergen-induced in vitro expression of IL-18, SLAM and GATA-3 mRNA in PBMC during sublingual immunotherapy. Allergy 2007;62:949953.
  • 27
    Fujimura T, Yonekura S, Taniguchi Y, Horiguchi S, Saito A, Yasueda H et al. The induced regulatory T cell level, defined as the proportion of IL-10Foxp3(+) cells among CD25(+)CD4(+) leukocytes, is a potential therapeutic biomarker for sublingual immunotherapy: a preliminary report. Int Arch Allergy Immunol 2010;153:378387.
  • 28
    Piconi S, Trabattoni D, Rainone V, Borgonovo L, Passerini S, Rizzardini G et al. Immunological effects of sublingual immunotherapy: clinical efficacy is associated with modulation of programmed cell death ligand 1, IL-10, and IgG4. J Immunol 2010;185:77237730.
  • 29
    Marcucci F, Sensi L, Di CG, Incorvaia C, Frati F. Dose dependence of immunological response to sublingual immunotherapy. Allergy 2005;60:952956.
  • 30
    Brimnes J, Kildsgaard J, Jacobi H, Lund K. Sublingual immunotherapy reduces allergic symptoms in a mouse model of rhinitis. Clin Exp Allergy 2007;37:488497.
  • 31
    Larche M, Akdis CA, Valenta R. Immunological mechanisms of allergen-specific immunotherapy. Nat Rev Immunol 2006;6:761771.
  • 32
    Akdis CA, Barlan IB, Bahceciler N, Akdis M. Immunological mechanisms of sublingual immunotherapy. Allergy 2006;61(Suppl 81):1114.
  • 33
    Moingeon P, Batard T, Fadel R, Frati F, Sieber J, Van OL. Immune mechanisms of allergen-specific sublingual immunotherapy. Allergy 2006;61:151165.
  • 34
    Kildsgaard J, Brimnes J, Jacobi H, Lund K. Sublingual immunotherapy in sensitized mice. Ann Allergy Asthma Immunol 2007;98:366372.
  • 35
    Pfaar O, Barth C, Jaschke C, Hormann K, Klimek L. Sublingual allergen-specific immunotherapy adjuvanted with monophosphoryl lipid A: a phase I/IIa study. Int Arch Allergy Immunol 2010;154:336344.
  • 36
    Mascarell L, Van OL, Moingeon P. Novel ways for immune intervention in immunotherapy: mucosal allergy vaccines. Immunol Allergy Clin North Am 2006;26:283-viii.
  • 37
    Sun JB, Cuburu N, Blomquist M, Li BL, Czerkinsky C, Holmgren J. Sublingual tolerance induction with antigen conjugated to cholera toxin B subunit induces Foxp3+CD25+CD4+ regulatory T cells and suppresses delayed-type hypersensitivity reactions. Scand J Immunol 2006;64:251259.
  • 38
    Van OL, Moussu H, Horiot S, Samson S, Lombardi V, Mascarell L et al. Lactic acid bacteria as adjuvants for sublingual allergy vaccines. Vaccine 2010;28:29862992.
  • 39
    Van OL, Lombardi V, Razafindratsita A, Saint-Lu N, Horiot S, Moussu H et al. IL-10-inducing adjuvants enhance sublingual immunotherapy efficacy in a murine asthma model. Int Arch Allergy Immunol 2007;145: 152162.
  • 40
    Klavinskis LS, Barnfield C, Gao L, Parker S. Intranasal immunization with plasmid DNA-lipid complexes elicits mucosal immunity in the female genital and rectal tracts. J Immunol 1999;162:254262.
  • 41
    Razafindratsita A, Saint-Lu N, Mascarell L, Berjont N, Bardon T, Betbeder D et al. Improvement of sublingual immunotherapy efficacy with a mucoadhesive allergen formulation. J Allergy Clin Immunol 2007;120:278285.
  • 42
    Bagnasco M, Altrinetti V, Pesce G, Caputo M, Mistrello G, Falagiani P et al. Pharmacokinetics of Der p 2 allergen and derived monomeric allergoid in allergic volunteers. Int Arch Allergy Immunol 2005;138:197202.