Advertisement

Guiding principles of sublingual immunotherapy for allergic rhinitis in Japanese patients

Published:November 23, 2015DOI:https://doi.org/10.1016/j.anl.2015.08.015

      Abstract

      Objective

      Sublingual immunotherapy (SLIT) appears to offer practical advantages for the treatment of allergic rhinitis (AR). Based on a review of the scientific literature, we present recommendations as guiding principles to administer SLIT safely.

      Methods

      Clinical questions concerning SLIT were prepared. Literature published between January 2003 and December 2012 was searched from PubMed, the Cochrane Library, and Japana Centra Revuo Medicina. Qualified studies were analyzed and the results were evaluated, consolidated, and codified. We answered 17 clinical questions and, based on this, presented evidence-based recommendations.

      Results

      Sublingual immunotherapy improved symptoms (e.g., quality of life [QOL]) and reduced medication scores in seasonal AR and perennial AR. Most SLIT-induced adverse effects were local oral reactions, although systemic adverse effects such as gastrointestinal symptoms, urticaria, and asthma are occasionally reported. There have been no reports of lethal anaphylactic reactions by SLIT. When SLIT is continued for 3–4 years, its effect persists long after discontinuation.

      Conclusion

      A correct diagnosis of AR and sufficient informed consent from patients are required before initiating SLIT. Sublingual immunotherapy should be continued for 3 years or longer. The initial administration of SLIT during the uptitration of an allergen vaccine and the general condition of patients are critical for the safe performance of SLIT.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Auris Nasus Larynx
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Yamada T.
        • Saito H.
        • Fujieda S.
        Present state of Japanese cedar pollinosis: the national affliction.
        J Allergy Clin Immunol. 2014; 133: 632-639
        • Sakashita M.
        • Hirota T.
        • Harada M.
        • Nakamichi R.
        • Tsunoda T.
        • Osawa Y.
        • et al.
        Prevalence of allergic rhinitis and sensitization to common aeroallergens in a Japanese population.
        Int Arch Allergy Immunol. 2010; 151: 255-261
        • Okamoto Y.
        • Ohta N.
        • Okano M.
        • Kamijo A.
        • Gotoh M.
        • Suzuki M.
        • et al.
        Guiding principles of subcutaneous immunotherapy for allergic rhinitis in Japan.
        Aurus Nasus Larynx. 2014; 41: 1-5
        • Fujieda S.
        • Kurono Y.
        • Okubo K.
        • Ichimura K.
        • Enomoto T.
        • Kawauchi H.
        • et al.
        Examination, diagnosis and classification for Japanese allergic rhinitis: Japanese guideline.
        Auris Nasus Larynx. 2012; 39: 553-556
        • Okubo K.
        • Kurono Y.
        • Fujieda S.
        • Ogino S.
        • Uchino E.
        • Odajima H.
        • et al.
        Japanese guideline for allergic rhinitis 2014.
        Allergol Int. 2014; 63: 357-375
        • Okubo K.
        • Gotoh M.
        • Fujieda S.
        • Okano M.
        • Yoshida H.
        • Morikawa H.
        • et al.
        A randomized double-blind comparative study of sublingual immunotherapy for cedar pollinosis.
        Allergol Int. 2008; 57: 265-275
        • Horiguchi S.
        • Okamoto Y.
        • Yonekura S.
        • Okawa T.
        • Yamamoto H.
        • Kunii N.
        • et al.
        A randomized controlled trial of sublingual immunotherapy for Japanese cedar pollinosis.
        Int Arch Allergy Immunol. 2008; 146: 76-84
      1. A guide to sublingual immunotherapy for allergic rhinitis.
        Jpn J Rhinol. 2014; 52 ([in Japanese]): 579-600
        • Radulovic S.
        • Wilson D.
        • Calderon M.
        • Durham S.
        Systematic review of sublingual immunotherapy (SLIT).
        Allergy. 2011; 66: 740-752
        • Lin S.Y.
        • Erekosima N.
        • Kim J.M.
        • Ramanathan M.
        • Suarez-Cuervo C.
        • Chelladurai Y.
        • et al.
        Sublingual immunotherapy for the treatment of allergic rhinoconjunctivitis and asthma.
        JAMA. 2013; 309: 1278-1288
        • Di Bona D.D.
        • Plaia A.
        • Scafidi V.
        • Leto-Barone M.S.
        • Di Lorenzo G.
        Efficacy of sublingual immunotherapy with grass allergens for seasonal allergic rhinitis: a systemic review and meta-analysis.
        J Allergy Clin Immunol. 2010; 126: 558-566
        • Yuta A.
        • Miyamoto Y.
        • Ogihara H.
        • Hattori R.
        • Okubo K.
        Antigen specific sublingual immunotherapy for pediatric Japanese cedar pollinosis.
        Arerugi. 2009; 58 ([in Japanese]): 124-132
        • Radulovic S.
        • Calderon M.A.
        • Wilson D.
        • Durham S.
        Sublingual immunotherapy for allergic rhinitis.
        Cochrane Database Syst Rev. 2012; 8: 1-140
        • Compalati E.
        • Passalacqua G.
        • Bonini M.
        • Canonica G.W.
        The efficacy of sublingual immunotherapy for house dust mites respiratory allergy: results of a GA2LEN meta-analysis. The efficacy of sublingual immunotherapy for house dust mites respiratory allergy: results of a GA2LEN meta-analysis.
        Allergy. 2009; 64: 1570-1579
        • Bozek A.
        • Ignasiak B.
        • Filipowska B.
        • Jarzab J.
        House dust mite sublingual immunotherapy: a double-blind, placebo-controlled study in elderly patients with allergic rhinitis.
        Clin Exp Allergy. 2013; 43: 242-248
        • Tahamiler R.
        • Saritzali G.
        • Canakcioglu S.
        Long-term efficacy of sublingual immunotherapy in patients with perennial rhinitis.
        Laryngoscope. 2007; 117: 965-969
        • Sopo S.M.
        • Macchiaiolo M.
        • Zorzi G.
        • Tripodi S.
        Sublingual immunotherapy in asthma and rhinoconjunctivitis; systematic review of pediatric literature.
        Arch Dis Child. 2004; 89: 620-624
        • Larenas-Linnemann D.
        • Blaiss M.
        • Van Bever H.P.
        • Compalati E.
        • Baena-Cagnani C.E.
        Pediatric sublingual immunotherapy efficacy: evidence analysis, 2009-2012.
        Ann Allergy Asthma Immunol. 2013; 110: 402-415
        • 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: 141-148
        • Eifan A.O.
        • Akkoc T.
        • Yildiz A.
        • Keles S.
        • Ozdemir C.
        • Bahceciler N.N.
        • et al.
        Clinical efficacy and immunological mechanisms of sublingual and subcutaneous immunotherapy in asthmatic/rhinitis children sensitized to house dust mite: an open randomized controlled trial.
        Clin Exp Allergy. 2010; 40: 922-932
        • Röder E.
        • Berger M.Y.
        • de Groot H.
        • van Wijk R.G.
        Immunotherapy in children and adolescents with allergic rhinoconjunctivitis: a systematic review.
        Pediatr Allergy Immunol. 2008; 19: 197-207
        • Smith H.
        • White P.
        • Annila I.
        • Poole J.
        • Andre C.
        • Frew A.
        Randomized controlled trial of high-dose sublingual immunotherapy to treat seasonal allergic rhinitis.
        J Allergy Clin Immunol. 2004; 114: 831-837
        • Durham S.R.
        • Emminger W.
        • Kapp A.
        • de Monchy J.G.
        • Rak S.
        • Scadding G.K.
        • et al.
        SQ-standardized sublingual grass immunotherapy: confirmation of disease modification 2 years after 3 years of treatment in a randomized trial.
        J Allergy Clin Immunol. 2012; 129: 717-725
        • Di Rienzo V.
        • Marcucci F.
        • Puccinelli P.
        • Parmiani S.
        • Frati F.
        • Sensi L.
        • et al.
        Long-lasting effect of sublingual immunotherapy in children with asthma due to house dust mite: a 10-year prospective study.
        Clin Exp Allergy. 2003; 33: 206-210
        • Novembre E.
        • Galli E.
        • Landi F.
        • Caffarelli C.
        • Pifferi M.
        • De Marco E.
        • et al.
        Coseasonal sublingual immunotherapy reduces the development of asthma in children with allergic rhinoconjunctivitis.
        J Allergy Clin Immunol. 2004; 114: 851-857
        • Marogna M.
        • Tomassetti D.
        • Bernasconi A.
        • Colombo F.
        • Massolo A.
        • Businco A.D.
        • et al.
        Preventive effects of sublingual immunotherapy in childhood: an open randomized controlled study.
        Ann Allergy Asthma Immunol. 2008; 101: 206-211
        • Marogna M.
        • Spadolini I.
        • Massolo A.
        • Canonica G.W.
        • Passalacqua G.
        Long-lasting effects of sublingual immunotherapy according to its duration: a 15-year prospective study.
        J Allergy Clin Immunol. 2010; 126: 969-975
        • Marogna M.
        • Spadolini I.
        • Massolo A.
        • Canonica G.W.
        • Passalacqua G.
        Clinical, functional, and immunologic effects of sublingual immunotherapy in birch pollinosis: a 3-year randomized controlled study.
        J Allergy Clin Immunol. 2005; 115: 1184-1188
        • Calderon M.A.
        • Penagos M.
        • Sheikh A.
        • Canonica G.W.
        • Durham S.R.
        Sublingual immunotherapy for allergic conjunctivitis: Cochrane systematic review and meta-analysis.
        Clin Exp Allergy. 2011; 41: 1263-1272
        • Webber C.M.
        • England R.W.
        Oral allergy syndrome: a clinical, diagnostic, and therapeutic challenge.
        Ann Allergy Asthma Immunol. 2010; 104: 101-108
        • Ciprandi G.
        • Cadario G.
        • Di Gioacchino G.M.
        • Gangemi S.
        • Gasparini A.
        • Isola S.
        • et al.
        Sublingual immunotherapy in children with allergic polysensitization.
        Allergy Asthma Proc. 2010; 31: 227-231
        • Durham S.R.
        • Emminger W.
        • Kapp A.
        • Colombo G.
        • de Monchy J.G.
        • 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: 131-138
        • Potter P.C.
        Update on sublingual immunotherapy.
        Ann Allergy Asthma Immunol. 2006; 96: S22-S25
        • Passalacqua G.
        • Villa G.
        • Altrinetti V.
        • Falagiani P.
        • Canonica G.W.
        • Mariani G.
        • et al.
        Sublingual swallow or spit?.
        Allergy. 2001; 56: 578
        • Dunsky E.H.
        • Goldstein M.F.
        • Dvorin D.J.
        • Falagiani P.
        • Canonica G.W.
        • Mariani G.
        • et al.
        Anaphylaxis to sublingual immunotherapy.
        Allergy. 2006; 61: 1235
        • Eifan A.O.
        • Keles S.
        • Bahceciler N.N.
        • Barlan I.B.
        Anaphylaxis to multiple pollen allergen sublingual immunotherapy.
        Allergy. 2007; 62: 567-568
        • Blazowski L.
        Anaphylactic shock because of sublingual immunotherapy overdose during third year of maintenance dose.
        Allergy. 2008; 63: 374
        • Wahn U.
        • Klimek L.
        • Ploszczuk A.
        • Adelt T.
        • Sandner B.
        • Trebas-Pietras E.
        • et al.
        High-dose sublingual immunotherapy with single-dose aqueous pollen extract in children is effective and safe: a double-blind, placebo-controlled study.
        J Allergy Clin Immunol. 2012; 130: 886-893
        • Stelmach I.
        • Kaluzinska-Parzyszek I.
        • Jerzynska J.
        • Stelmach P.
        • Stelmach W.
        • Majak P.
        Comparative effect of pre-coseasonal and continuous grass sublingual immunotherapy in children.
        Allergy. 2012; 67: 312-320
        • Didier A.
        • Worm M.
        • Horak F.
        • Sussman G.
        • de Beaumont O.
        • Le Gall M.
        • et al.
        Sustained 3-year efficacy of pre- and coseasonal 5-grass-pollen sublingual immunotherapy tablets in patients with grass pollen-induced rhinoconjunctivitis.
        J Allergy Clin Immunol. 2011; 128: 559-566
        • Lombardi C.
        • Incorvaia C.
        • Braga M.
        • Senna G.
        • Canonica G.W.
        • Passalacqua G.
        Administration regimens for sublingual immunotherapy to pollen allergens: what do we know?.
        Allergy. 2009; 64: 849-854
        • Mösges R.
        • Graute V.
        • Christ H.
        • Sieber H.J.
        • Wahn U.
        • Niggemann B.
        Safety of ultra-rush titration of sublingual immunotherapy in asthmatic children with tree-pollen allergy.
        Pediatr Allergy Immunol. 2010; 21: 1135-1138
        • Ott H.
        • Sieber J.
        • Brehler R.
        • Fölster-Holst R.
        • Kapp A.
        • Klimek L.
        • et al.
        Efficacy of grass pollen sublingual immunotherapy for three consecutive seasons and after cessation of treatment: the ECRIT study.
        Allergy. 2009; 64: 1394-1401
        • Agostinis F.
        • Foglia C.
        • Bruno M.E.
        • Falagiani P.
        Efficacy, safety and tolerability of sublingual monomeric allergoid in tablets given without up-dosing to pediatric patients with allergic rhinitis and/or asthma due to grass pollen.
        Eur Ann Allergy Clin Immunol. 2009; 41: 177-180
        • Moreno-Ancillo A.
        • Moreno C.
        • Ojeda P.
        • Domínguez C.
        • Barasona M.J.
        • García-Cubillana A.
        • et al.
        Efficacy and quality of life with once-daily sublingual immunotherapy with grasses plus olive pollen extract without updosing.
        J Investig Allergol Clin Immunol. 2007; 17: 399-405
        • Durham S.
        • Yang W.
        • Pedersen M.
        • 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: 802-809
        • Guerra L.
        • Compalati E.
        • Rogkakou A.
        • Pecora S.
        • Passalacqua G.
        • Canonica G.W.
        Randomized open comparison of the safety of SLIT in a no-updosing and traditional updosing schedule in patients with Parietaria allergy.
        Allergol Immunopathol. 2006; 34: 82-83
        • de Groot H.
        • Bijl A.
        Anaphylactic reaction after the first dose of sublingual immunotherapy with grass pollen tablet.
        Allergy. 2009; 64: 963-964
        • Didier A.
        • Malling H.J.
        • Worm M.
        • Horak F.
        • Jäger 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: 1338-1345
        • Sieber J.
        • Köberlein J.
        • Mösges R.
        Sublingual immunotherapy in daily medical practice: effectiveness of different treatment schedules – IPD meta-analysis.
        Curr Med Res Opin. 2010; 26: 925-932
        • Mösges 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® tablet.
        Acta Dermatovenerol Alp Pannonica Adriat. 2010; 19: 3-10
        • Cox L.S.
        • Larenas Linnemann D.
        • Nolte H.
        • Weldon D.
        • Finegold I.
        • Nelson H.S.
        Sublingual immunotherapy: a comprehensive review.
        J Allergy Clin Immunol. 2006; 117: 1021-1035
        • Wise S.K.
        • Schlosser R.J.
        Evidence-based practice: sublingual immunotherapy for allergic rhinitis.
        Otolaryngol Clin North Am. 2012; 45: 1045-1054
        • Khinchi M.S.
        • Poulsen L.K.
        • Carat F.
        • André C.
        • Hansen A.B.
        • Malling H.J.
        Clinical efficacy of sublingual and subcutaneous birch pollen allergen-specific immunotherapy: a randomized, placebo-controlled, double-blind, double-dummy study.
        Allergy. 2004; 59: 45-53
        • Sieber J.
        • Shah-Hosseini K.
        • Mösges R.
        Specific immunotherapy for allergic rhinitis to grass and tree pollens in daily medical practice-symptom load with sublingual immunotherapy compared to subcutaneous immunotherapy.
        Ann Med. 2011; 43: 418-424
        • Di Bona D.
        • Plaia A.
        • Leto-Barone M.S.
        • La Piana S.
        • Di Lorenzo G.
        Efficacy of subcutaneous and sublingual immunotherapy with grass allergens for seasonal allergic rhinitis: a meta-analysis-based comparison.
        J Allergy Clin Immunol. 2012; 130: 1097-1107
        • Yukselen A.
        • Kendirli S.G.
        • Yilmaz M.
        • Altintas D.U.
        • Karakoc G.B.
        Effect of one-year subcutaneous and sublingual immunotherapy on clinical and laboratory parameters in children with rhinitis and asthma: a randomized, placebo-controlled, double-blind, double-dummy study.
        Int Arch Allergy Immunol. 2012; 157: 288-298
        • Wise S.K.
        • Schlosser R.J.
        Subcutaneous and sublingual immunotherapy for allergic rhinitis: what is the evidence?.
        Am J Rhinol Allergy. 2012; 26: 18-22
        • Passalacqua G.
        • Baena-Cagnani C.E.
        • Bousquet J.
        • Canonica G.W.
        • Casale T.B.
        • Cox L.
        • et al.
        Grading local side effects of sublingual immunotherapy for respiratory allergy: speaking the same language.
        J Allergy Clin Immunol. 2013; 132: 93-98
        • Zuberbier T.
        • Bachert C.
        • Bousquet P.J.
        • Passalacqua G.
        • Walter Canonica G.
        • Merk H.
        • et al.
        GA2 LEN/EAACI pocket guide for allergen-specific immunotherapy for allergic rhinitis and asthma.
        Allergy. 2010; 65: 1525-1530
        • Walker S.M.
        • Durham S.R.
        • Till S.J.
        • Roberts G.
        • Corrigan C.J.
        • Leech S.C.
        • et al.
        Immunotherapy for allergic rhinitis.
        Clin Exp Allergy. 2011; 41: 1177-1200
        • DuBuske L.M.
        Appropriate and inappropriate use of immunotherapy.
        Ann Allergy Asthma Immunol. 2001; 87: 56-67
        • Mascarell L.
        • Lombardi V.
        • Louise A.
        • Saint-Lu N.
        • Chabre H.
        • Moussu H.
        • et al.
        Oral dendritic cells mediate antigen-specific tolerance by stimulating TH1 and regulatory CD4+ T cells.
        J Allergy Clin Immunol. 2008; 122: 603-609
        • Novak N.
        • Haberstok J.
        • Bieber T.
        • Allam J.P.
        The immune privilege of the oral mucosa.
        Trends Mol Med. 2008; 14: 191-198
        • Allam J.P.
        • Novak N.
        • Fuchs C.
        • Asen S.
        • Bergé 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: 141-148
        • Mascarell L.
        • Lombardi V.
        • Zimmer A.
        • Louise A.
        • Tourdot S.
        • Van Overtvelt L.
        • et al.
        Mapping of the lingual immune system reveals the presence of both regulatory and effector CD4+ T cells.
        Clin Exp Allergy. 2009; 39: 1910-1919
        • Allam J.P.
        • 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: 720-727
        • Canonica G.W.
        • Bousquet J.
        • Casale T.
        • Lockey R.F.
        • Baena-Cagnani C.E.
        • Pawankar R.
        • et al.
        Sub-lingual immunotherapy: World Allergy Organization Position Paper 2009.
        Allergy. 2009; 64: 1-59
        • Calderón M.A.
        • Simons F.E.
        • Malling H.J.
        • Lockey R.F.
        • Moingeon P.
        • Demoly P.
        Sublingual allergen immunotherapy: mode of action and its relationship with the safety profile.
        Allergy. 2012; 67: 302-311
        • Lima M.T.
        • Wilson D.
        • Pitkin L.
        • Roberts A.
        • Nouri-Aria K.
        • Jacobson M.
        • et al.
        Grass pollen sublingual immunotherapy for seasonal rhinoconjunctivitis: a randomized controlled trial.
        Clin Exp Allergy. 2002; 32: 507-514
        • Allam J.P.
        • Peng W.M.
        • 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 (368–374.e1)
        • Allam J.P.
        • Würtzen P.A.
        • Reinartz M.
        • Winter J.
        • Vrtala S.
        • Chen K.W.
        • 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: 638-645
        • Novak N.
        • Bieber T.
        • Allam J.P.
        Immunological mechanisms of sublingual allergen-specific immunotherapy.
        Allergy. 2011; 66: 733-739
        • Scadding G.W.
        • Shamji M.H.
        • Jacobson M.R.
        • Lee D.I.
        • Wilson D.
        • Lima M.T.
        • 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: 598-606
        • Sakaguchi S.
        • Yamaguchi T.
        • Nomura T.
        • Ono M.
        Regulatory T cells and immune tolerance.
        Cell. 2008; 133: 775-787
        • Schandené L.
        • Alonso-Vega C.
        • Willems F.
        • Gérard C.
        • Delvaux A.
        • Velu T.
        • et al.
        B7/CD28-dependent IL-5 production by human resting T cells is inhibited by IL-10.
        J Immunol. 1994; 152: 4368-4374
        • Taylor A.
        • Verhagen J.
        • Blaser K.
        • Akdis M.
        • Akdis C.A.
        Mechanisms of immune suppression by interleukin-10 and transforming growth factor-beta: the role of T regulatory cells.
        Immunology. 2006; 117: 433-442
        • Dons E.M.
        • Raimondi G.
        • Cooper D.K.
        • Thomson A.W.
        Induced regulatory T cells: mechanisms of conversion and suppressive potential.
        Hum Immunol. 2012; 73: 328-334
        • Gri G.
        • Piconese S.
        • Frossi B.
        • Manfroi V.
        • Merluzzi S.
        • Tripodo C.
        • et al.
        CD4+CD25+ regulatory T cells suppress mast cell degranulation and allergic responses through OX40-OX40L interaction.
        Immunity. 2008; 29: 771-781
        • Radulovic S.
        • Jacobson M.R.
        • Durham S.R.
        • Nouri-Aria K.T.
        Grass pollen immunotherapy induces Foxp3-expressing CD4+ CD25+ cells in the nasal mucosa.
        J Allergy Clin Immunol. 2008; 121: 1467-1472
        • 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: 7723-7730
        • Ciprandi G.
        • De Amici M.
        • Marseglia G.
        • Fuchs D.
        Sublingual immunotherapy may affect serum neopterin: preliminary findings.
        Int Immunopharmacol. 2010; 10: 1474-1476
        • Ciprandi G.
        • Contini P.
        • Pistorio A.
        • Murdaca G.
        • Puppo F.
        Sublingual immunotherapy reduces soluble HLA-G and HLA-A,-B-C serum levels in patients with allergic rhinitis.
        Int Immunopharmacol. 2009; 9: 253-257
        • 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-10(+) Foxp3(+) cells among CD25(+)CD4(+) leukocytes, is a potential therapeutic biomarker for sublingual immunotherapy: a preliminary report.
        Int Arch Allergy Immunol. 2010; 153: 378-387
        • Fujimura T.
        • Yonekura S.
        • Horiguchi S.
        • Taniguchi Y.
        • Saito A.
        • Yasueda H.
        • et al.
        Increase of regulatory T cells and the ratio of specific IgE to total IgE are candidates for response monitoring or prognostic biomarkers in 2-year sublingual immunotherapy (SLIT) for Japanese cedar pollinosis.
        Clin Immunol. 2011; 139: 65-74
        • Makino Y.
        • Noguchi E.
        • Takahashi N.
        • Matsumoto Y.
        • Kubo S.
        • Yamada T.
        • et al.
        Apolipoprotein A-IV is a candidate target molecule for the treatment of seasonal allergic rhinitis.
        J Allergy Clin Immunol. 2010; 126: 1163-1169