Local and systemic allergen-specific IgA and IgG antibody responses differ between grass pollen subcutaneous and sublingual immunotherapy

Published: April 2, 2021

Grass pollen allergen immunotherapy can be administered either by the subcutaneous (SCIT) or the sublingual (SLIT) route; both are clinically effective and associated with the induction of allergen-specific antibodies. There has been no direct comparison of the magnitude nor immunoglobulin isotype specificity of the local nasal nor systemic antibody responses between the two routes.

In a recent article published in The Journal of Allergy and Clinical Immunology (JACI), Shamji and colleagues studied sera and nasal fluid collected during the GRASS trial (Gauging Response in Allergic Rhinitis to Sublingual and Subcutaneous Immunotherapy Scadding GW et al., JAMA 2017; 317: 615-25). In this double-blind double-dummy comparison, samples were collected at baseline and annually for 2 years during treatment and at one year following treatment withdrawal. Both treatments were effective compared to placebo in suppressing the response to grass pollen nasal challenge, although the effect was lost at year 3. Grass pollen-specific IgA1, IgA2, IgG4, IgG and IgE were measured in sera and nasal fluids. Additionally, Specific IgE and IgG4 responses to the major grass pollen allergens Phl p1, 2, 4, 5b, 6, 7, 11 and 12 were measured in sera.

GP-specific IgA1 and IgA2 concentrations were elevated in nasal fluid in participants receiving SLIT compared to SCIT and placebo at year 2 and 3. IgA1 in serum was elevated in SLIT compared to SCIT and placebo at years 1, 2, and 3. In contrast, local nasal and serum IgG and IgG4 were consistently higher in SCIT compared to SLIT and serum IgG4 to Phl p1, 2, 5b and 6 were increased in both groups compared to placebo at years 1, 2 and 3. Local nasal  GP-specific IgE concentrations were increased in the SLIT-treated group at year 2, but not year 3 compared to SCIT and placebo-treated groups. When immunoglobulin data were added to a hierarchical clustering analysis, the ability to cluster participants by treatment group and response to treatment was enhanced.

Enhanced induction of IgA in SLIT as compared to IgG4 in SCIT represents a key difference in the immunologic effects of these treatments.  The role of IgA in SLIT needs to be further explored.

The Journal of Allergy and Clinical Immunology (JACI) is an official scientific journal of the AAAAI, and is the most-cited journal in the field of allergy and clinical immunology.

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