Nasal allergen-neutralizing IgG4 antibodies block IgE-mediated responses: Novel biomarker of subcutaneous grass pollen immunotherapy

Abstract

Background: Grass pollen subcutaneous immunotherapy (SCIT) is associated with induction of serum IgG 4-associated inhibitory antibodies that prevent IgE-facilitated allergen binding to B cells. Objective: We sought to determine whether SCIT induces nasal allergen-specific IgG 4 antibodies with inhibitory activity that correlates closely with clinical response. Methods: In a cross-sectional controlled study, nasal fluid and sera were collected during the grass pollen season from 10 SCIT-treated patients, 13 untreated allergic patients (with seasonal allergic rhinitis [SAR]), and 12 nonatopic control subjects. Nasal and serum IgE and IgG 4 levels to Phleum pratense components were measured by using the Immuno Solid Allergen Chip microarray. Inhibitory activity was measured by IgE-facilitated allergen binding assay. IL-10 1 regulatory B cells were quantified in peripheral blood by using flow cytometry. Results: Nasal and serum Phl p 1-and Phl p 5-specific IgE levels were increased in patients with SAR compared to nonatopic control subjects (all, P < .001) and SCIT-treated patients (nasal, P < .001; serum Phl p 5, P 5 .073). Nasal IgG 4 levels were increased in the SCIT group compared to those in the SAR group (P < .001) during the pollen season compared to out of season. IgG-associated inhibitory activity in nasal fluid and serum was significantly increased in the SCIT group compared to that in the SAR (both, P < .01). The magnitude of the inhibitory activity was 93% (P < .

Broad IgG repertoire in patients with chronic rhinosinusitis with nasal polyps regulates proinflammatory IgE responses

“…17,26,27 IgG 4 depletion results in the recovery of allergen-IgE binding to B cells. 26,32 In this study we also observed the regulatory role of IgG antibody in nasal polyp homogenates of patients with CRSwNP. IgG-regulated FcεRII (CD23) mediated IgE-facilitated allergen presentation by B to T cells.…”

Relationship between serum inhibitory activity for IgE and efficacy of Artemisia pollen subcutaneous immunotherapy for allergic rhinitis: a preliminary self-controlled study

“…Allergen specific IgG4s are bispecific antibodies that may block antigenic epitopes and act as blocking antibodies and it may be responsible for postimmunotherapy serum inhibitory for IgE [12]. By ELIFAB, it was found that serum inhibitory activity for IgE increased significantly after SCIT (P < 0.05) and correlated moderately with levels Table 2 Sensitization of AR-sIgG4 (r = − 0.501,P < 0.01), as in former studies [10,11]. However, there is no significant relationship between serum inhibitory activity for IgE and clinical improvements, which is different from what have been reported.…”

“…As a part of it, the inhibition of binding of IgE-allergen complexes to B cells can be tested by the IgE-FAB assay [9]. It has been demonstrated that the serum inhibitory activity for IgE, determined by the IgE-FAB assay, increased after AIT and had relevance with the clinical improvements [10,11]. Moreover, it has been recommended as potential biomarker for efficacy of AIT in 2017 EAACI Position Paper [12].…”

“…Moreover, it has been recommended as potential biomarker for efficacy of AIT in 2017 EAACI Position Paper [12]. It seems that the allergen specific IgGs, especially IgG4s, play a key role in the inhibitory activity for IgE, as the depletion of total IgGs lead to the reduction of the inhibition [11,13] and it has close relationship with serum levels of sIgG4 [11]. Although the IgE-FAB assay is reproducible, it is complex and limited to specialized centers or laboratories.…”

IgE antibody repertoire in nasal secretions of children and adults with seasonal allergic rhinitis: A molecular analysis

“…15,16 Moreover, nasal specific IgE (N-sIgE) has been proposed as a control parameter for the efficacy of allergen-specific immunotherapy (AIT). [17][18][19] IgE testing in NS has been also suggested as a potentially beneficial non-invasive tool to identify the local onset of IgE production in small children. 20,21 Many efforts have been made to standardize the methodology of NS collection.…”