Differential induction of allergen-specific IgA responses following timothy grass subcutaneous and sublingual immunotherapy

• Published in: Journal of allergy and clinical immunology Vol. 148; no. 4; pp. 1061 - 1071.e11
• Main Authors: Shamji, Mohamed H., Larson, David, Eifan, Aarif, Scadding, Guy W., Qin, Tielin, Lawson, Kaitie, Sever, Michelle L., Macfarlane, Ellen, Layhadi, Janice A., Würtzen, Peter A., Parkin, Rebecca V., Sanda, Srinath, Harris, Kristina M., Nepom, Gerald T., Togias, Alkis, Durham, Stephen R.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-10-2021
• Subjects: Administration, Sublingual; Adult; Allergens - immunology; allergic rhinitis; B-Lymphocytes - immunology; blocking antibodies; Desensitization, Immunologic; Double-Blind Method; Female; Humans; IgA1; IgA2; IgE-FAB; IgG4; Immunoglobulins - blood; Immunoglobulins - immunology; Injections, Subcutaneous; Male; Nasal Mucosa - immunology; Phleum - immunology; Pollen - immunology; subcutaneous immunotherapy; Sublingual immunotherapy; PP; SLIT; IgG4; IgE-FAB; IgA1; AIT; Sublingual immunotherapy; IgA2; AUC; NAC; subcutaneous immunotherapy; GRASS; blocking antibodies; allergic rhinitis; Phl p; TGP; SCIT; TNSS; IgA; IgG
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2021.03.030

There is no detailed comparison of allergen-specific immunoglobulin responses following sublingual immunotherapy (SLIT) and subcutaneous immunotherapy (SCIT).
We sought to compare nasal and systemic timothy grass pollen (TGP)-specific antibody responses during 2 years of SCIT and SLIT and 1 year after treatment discontinuation in a double-blind, double-dummy, placebo-controlled trial.
Nasal fluid and serum were obtained yearly (per-protocol population, n = 84). TGP-specific IgA1, IgA2, IgG4, IgG, and IgE were measured in nasal fluids by ELISA. TGP-specific IgA1, IgA2, and Phleum pratense (Phl p)1, 2, 4, 5b, 6, 7, 11, and 12 IgE and IgG4 were measured in sera by ELISA and ImmunoCAP, respectively.
At years 2 and 3, TGP-IgA1/2 levels in nasal fluid were elevated in SLIT compared with SCIT (4.2- and 3.0-fold for IgA1, 2.0- and 1.8-fold for IgA2, respectively; all P < .01). TGP-IgA1 level in serum was elevated in SLIT compared with SCIT at years 1, 2, and 3 (4.6-, 5.1-, and 4.7-fold, respectively; all P < .001). Serum TGP-IgG level was higher in SCIT compared with SLIT (2.8-fold) at year 2. Serum TGP-IgG4 level was higher in SCIT compared with SLIT at years 1, 2, and 3 (10.4-, 27.4-, and 5.1-fold, respectively; all P < .01). Serum IgG4 levels to Phl p1, 2, 5b, and 6 were increased at years 1, 2, and 3 in SCIT and SLIT compared with placebo (Phl p1: 11.8- and 3.9-fold; Phl p2: 31.6- and 4.4-fold; Phl p5b: 135.5- and 5.3-fold; Phl p6: 145.4- and 14.7-fold, respectively, all at year 2 when levels peaked; P < .05). IgE to TGP in nasal fluid increased in the SLIT group at year 2 but not at year 3 compared with SCIT (2.8-fold; P = .04) and placebo (3.1-fold; P = .02). IgA to TGP and IgE and IgG4 to TGP components stratified participants according to treatment group and clinical response.
The observed induction of IgA1/2 in SLIT and IgG4 in SCIT suggest key differences in the mechanisms of action.
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