The blocking activity of birch pollen-specific immunotherapy-induced IgG4 is not qualitatively superior to that of other IgG subclasses

Ejrnaes, Anne M; Bødtger, Uffe; Larsen, Jørgen Nedergaard; Svenson, Morten

doi:10.1016/j.molimm.2004.04.018

Cited by 22 publications

(23 citation statements)

References 44 publications

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“…We have not been able to find significant alterations in IgG or IgG4 avidity by aeroallergen SIT [14, 29], which have been shown in insect venom studies [30, 31]. This supports that IgG4 contributes to the blocking activity by simple quantity rather than altered quality [32, 33].…”

Section: Discussionsupporting

confidence: 59%

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Is Immunotherapy-Induced Birch-Pollen-Specific IgG4 a Marker for Decreased Allergen-Specific Sensitivity?

Bødtger

Ejrnaes²,

Hummelshøj³

et al. 2005

Int Arch Allergy Immunol

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Background: The role of IgG4 during allergen-specific immunotherapy (SIT) is still controversial. The available studies present paramount differences in in vitro techniques, allergens, and clinical outcome parameters. By implementing a sensitive method, and pivotal clinical outcome parameters, we wanted to ascertain the utility of IgG4 as a clinical marker of decreased allergen-specific sensitivity to a common aeroallergen. Methods: Sera were drawn from 23 birch-pollen-allergic patients during a placebo-controlled clinical trial on birch pollen SIT. Seventeen patients received active treatment. Blood samples were drawn at 0, 2, 4, 7, and 30 treatment weeks, and 36 months. The binding activity of autologous IgG, IgG4, IgE, and IgE- and/or IgG-depleted serum to ¹²⁵I-labelled recombinant Bet v 1 was assessed in a fluid-phase radioimmunoassay. Disease severity was assessed subjectively on a visual analogue scale (VAS), and objectively by intradermal late-phase reaction diameters. Results: Before SIT IgG4 fraction of IgG-allergen binding varied from 4 to 74%, with a median of 36%, increasing to 71% after 36 months. Changes in IgG4 or IgG4/IgG fraction were not correlated to clinical outcome parameters. Changes in IgG allergen binding and VAS were significantly correlated (σ = 0.72; p < 0.05). SIT increased the serum-blocking activity of IgE allergen binding from 25% before SIT to 80% after SIT. No changes were observed in the placebo group. Conclusion: The data suggest that IgG4 per se is a poor marker of decreased allergen-specific sensitivity to birch pollen, both as a single measurement and as delta values.

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Section: Discussionsupporting

confidence: 59%

“…We have previously shown that IgG4 depletion resulted in equivalent reductions in binding and blocking activities of Bet v 1 to IgE [29]. We have not been able to find significant alterations in IgG or IgG4 avidity by aeroallergen SIT [14, 29], which have been shown in insect venom studies [30, 31].…”

Section: Discussionmentioning

confidence: 77%

Is Immunotherapy-Induced Birch-Pollen-Specific IgG4 a Marker for Decreased Allergen-Specific Sensitivity?

Bødtger

Ejrnaes²,

Hummelshøj³

et al. 2005

Int Arch Allergy Immunol

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“…by inhibiting IgE-mediated release of inflammatory mediators from mast cells and basophils or by preventing IgE-facilitated allergen presentation to T cells) (66,67). Because SIT with airborne allergens does not induce significant variations in IgG avidity (68)(69)(70), the blocking activity of IgG is presumably a quantitative function, which, at best, is reflected by the observed decrease in the serum IgE/IgG4 and IgE/IgG ratio in patients on SIT (71,72). Furthermore, it seems that the blocking activity is related to the epitope specificity rather than to the isotype.…”

Section: Discussionmentioning

confidence: 99%

Birch Pollen Immunotherapy Leads to Differential Induction of Regulatory T Cells and Delayed Helper T Cell Immune Deviation

Möbs

Slotosch

Löffler

et al. 2010

The Journal of Immunology

120

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Correction of an imbalance between allergen-specific T cell subsets is considered a critical event in establishing allergen tolerance by specific immunotherapy (SIT). In a comprehensive, longitudinal study, distinct T cell populations and Ig subtypes were analyzed in subjects allergic to birch pollen during decisive time points of SIT (i.e., induction and maintenance phase), as well as in and out of birch pollen season. An increase in Bet v 1-specific, IL-10–secreting T cells, fulfilling the criteria of inducible type 1 regulatory T (Tr1) cells, was observed by the end of the induction phase; this resulted in a decreased ratio of allergen-specific IL-5+ Th2/Tr1 cells. In contrast, CD4+CD25+CD127low regulatory T cell numbers did not change. Furthermore, enhanced concentrations of allergen-specific IgG Abs were observed, whereas allergen-specific IgE and IgA levels remained unchanged. After 1 y of SIT, a reduced ratio of allergen-specific Th2/IFN-γ+ Th1 cells was apparent. Although untreated and SIT-treated allergic subjects developed enhanced Th2 cell responses during birch pollen season, only SIT-treated patients experienced elevated numbers of allergen-specific Tr1 cells, which were associated with reduced skin prick test reactivity and diminished clinical symptoms. In coculture assays, allergen-specific Tr1 cells showed an IL-10– and dose-dependent inhibition of CD4+CD25− T effector cells. Thus, SIT has differential effects on regulatory T cell subsets, resulting in an early induction of allergen-specific Tr1 cells associated with an increase in allergen-specific IgG, and it leads to a delayed shift from an allergen-specific Th2- to a Th1-dominated immune response.

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“…Likewise, in birch pollen SIT no or minor changes were found in the Bet v 1 K d values of polyclonal IgG [103]. Furthermore it has been demonstrated that the blocking effect of specific IgG4 is not superior to that of other IgG subclasses [104]. Even though it is highly relevant, only few studies have addressed the presence of antibodies in the affected organs.…”

Section: Mechanisms and Immunological Changes Following Sit: Antibodymentioning

confidence: 99%

IgE-Mediated Allergen Presentation and Blocking Antibodies: Regulation of T-Cell Activation in Allergy

Neerven

Knol

Ejrnaes

et al. 2006

Int Arch Allergy Immunol

116

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It is well established that both the production of IgE by B lymphocytes and the maturation and recruitment of eosinophils in late-phase reactions are dependent on the activation of allergen-specific type-2 T-helper cells. What is less well known is the fact that efficient activation of allergen-specific T cells upon low-dose exposure to allergens is critically dependent on IgE-mediated or -facilitated allergen presentation. In fact, changes in the level of IgE-mediated allergen presentation may account for many of the immunological effects described for specific immunotherapy or anti-IgE treatment. This review aims to summarize the current knowledge, and will discuss the clinical relevance of blocking IgG antibodies induced by specific immunotherapy and anti-IgE monoclonal antibodies that both interfere with IgE-mediated allergen presentation.

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The blocking activity of birch pollen-specific immunotherapy-induced IgG4 is not qualitatively superior to that of other IgG subclasses

Cited by 22 publications

References 44 publications

Is Immunotherapy-Induced Birch-Pollen-Specific IgG4 a Marker for Decreased Allergen-Specific Sensitivity?

Is Immunotherapy-Induced Birch-Pollen-Specific IgG4 a Marker for Decreased Allergen-Specific Sensitivity?

Birch Pollen Immunotherapy Leads to Differential Induction of Regulatory T Cells and Delayed Helper T Cell Immune Deviation

IgE-Mediated Allergen Presentation and Blocking Antibodies: Regulation of T-Cell Activation in Allergy

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