title: Immunological effects of sublingual immunotherapy: clinical efficacy is associated with modulation of programmed cell death ligand 1, IL-10, and IgG4.
abstract: Sublingual immunotherapy (SLIT) is an alternate route of administration of allergen-specific immunotherapy with an improved safety profile; to clarify the immune mechanisms elicited by this therapy, we analyzed the clinical and immunologic effects of SLIT in patients with a clinical history of ragweed sensitization. To analyze possible difference among immunotherapeutic protocols, we also compared patients receiving preseasonal, seasonal, or prolonged sublingual therapy (≥ 3 y); patients receiving symptomatic therapy alone were enrolled as well in the study. Clinical and immunological parameters were measured twice in and out of the pollination period. Clinical benefits, as measured by the visual analog scale for symptoms and for use of drugs, were evident in all three groups of individuals receiving immunotherapy, but were significantly better in patients undergoing prolonged SLIT. Immunologically, SLIT resulted in increased IL-10 production, programmed cell death ligand 1 expression, and concentration of allergen-specific IgG4, as well as in the reduction of CD80 and CD86 expression and IL-4 production. SLIT, thus, is associated with modulation of programmed cell death ligand 1 expression and IL-10 synthesis and favors the production of allergen-specific IgG4. These effects are evident from the first pollen season, independently from therapeutic regimen (preseasonal or seasonal) even if a prolonged treatment is necessary to obtain full clinical efficacy. A more detailed understanding of the interaction of allergen and APCs within the oral mucosa will allow improved targeting of allergy vaccine.
authors.affiliation: Department of Allergic Diseases and Clinical Immunology, L. Sacco Hospital, Milan, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Piconi
authors.forename: Daria
authors.initials: D
authors.lastname: Trabattoni
authors.forename: Veronica
authors.initials: V
authors.lastname: Rainone
authors.forename: Linda
authors.initials: L
authors.lastname: Borgonovo
authors.forename: Simone
authors.initials: S
authors.lastname: Passerini
authors.forename: Giuliano
authors.initials: G
authors.lastname: Rizzardini
authors.forename: Franco
authors.initials: F
authors.lastname: Frati
authors.forename: Enrico
authors.initials: E
authors.lastname: Iemoli
authors.forename: Mario
authors.initials: M
authors.lastname: Clerici
mesh_terms: D000286:Administration, Sublingual; D000328:Adult; D000485:Allergens / Q000008:administration & dosage*; D000918:Antibody Specificity / Q000187:drug effects / Q000276:immunology*; D015703:Antigens, CD / Q000097:blood / Q000276:immunology*; D018122:B7-1 Antigen / Q000096:biosynthesis / Q000276:immunology; D051940:B7-2 Antigen / Q000096:biosynthesis / Q000276:immunology; D060890:B7-H1 Antigen; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology*; D007167:Immunotherapy / Q000379:methods*; D016753:Interleukin-10 / Q000097:blood / Q000276:immunology*; D015847:Interleukin-4 / Q000097:blood / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009061:Mouth Mucosa / Q000276:immunology / Q000378:metabolism; D012130:Respiratory Hypersensitivity / Q000628:therapy*; D014612:Vaccines / Q000008:administration & dosage*
chemical_list: D000485:Allergens; D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D060890:B7-H1 Antigen; C423236:CD274 protein, human; C497964:CD86 protein, human; C508609:IL10 protein, human; C508598:IL4 protein, human; D007074:Immunoglobulin G; D014612:Vaccines; D016753:Interleukin-10; D015847:Interleukin-4