On the complexity of IgE: The role of structural flexibility and glycosylation for binding its receptors.

It is well established that immunoglobulin E (IgE) plays a crucial role in atopy by binding to two types of Fcε receptors (FcεRI and FcεRII, also known as CD23). The cross-linking of FcεRI-bound IgE on effector cells, such as basophils and mast cells, initiates the allergic response. Conversely, the binding of IgE to CD23 modulates IgE serum levels and antigen presentation. In addition to binding to FcεRs, IgE can also interact with other receptors, such as certain galectins and, in mice, some FcγRs. The binding strength of IgE to its receptors is affected by its valency and glycosylation. While FcεRI shows reduced binding to IgE immune complexes (IgE-ICs), the binding to CD23 is enhanced. There is no evidence that galectins bind IgE-ICs. On the other hand, IgE glycosylation plays a crucial role in the binding to FcεRI and galectins, whereas the binding to CD23 seems to be independent of glycosylation. In this review, we will focus on receptors that bind to IgE and examine how the glycosylation and complexation of IgE impact their binding

Model sensitivity in the effect of Antarctic sea ice and stratification on atmospheric pCO2

Several recent papers have demonstrated a decrease in atmospheric pCO(2) resulting from barriers to communication between the deep sea and the atmosphere in the Southern Ocean. Stephens and Keeling [2000] decreased pCO(2) by increasing Antarctic sea ice in a seven-box model of the world ocean, and Toggweiler [1999] showed a similar response to Southern Ocean stratification. In box models the pCO(2) of the atmosphere is controlled by the region of the surface ocean that fills the deep sea [Archer et al., 2000a]. By severing the Southern Ocean link between the deep sea and the atmosphere, atmospheric pCO(2) in these models is controlled elsewhere and typically declines, although the models range widely in their responses. "Continuum models,'' such as three-dimensional (3-D) and 2-D general circulation models, control pCO(2) in a more distributed way and do not exhibit box model sensitivity to high-latitude sea ice or presumably stratification. There is still uncertainty about the high-latitude sensitivity of the real ocean. Until these model sensitivities can be resolved, glacial pCO(2) hypotheses and interpretations based on Southern Ocean barrier mechanisms (see above mentioned references plus Elderfield and Rickaby [2000], Francois et al. [1998], Gildor and Tziperman [2001], Sigman and Boyle [2000], and Watson et al. [2000]) are walking on thin ice

IgE glycans promote anti-IgE IgG autoantibodies that facilitate IgE serum clearance via Fc Receptors.

BACKGROUND Recent studies have shown that IgE glycosylation significantly impacts the ability of IgE to bind to its high-affinity receptor FcεRI and exert effector functions. We have recently demonstrated that immunizing mice with IgE in a complex with an allergen leads to a protective, glycan-dependent anti-IgE response. However, to what extent the glycans on IgE determine the induction of those antibodies and how they facilitate serum clearance is unclear.Therefore, we investigated the role of glycan-specific anti-IgE IgG autoantibodies in regulating serum IgE levels and preventing systemic anaphylaxis by passive immunization. METHODS Mice were immunized using glycosylated or deglycosylated IgE-allergen-immune complexes (ICs) to induce anti-IgE IgG antibodies. The anti-IgE IgG antibodies were purified and used for passive immunization. RESULTS Glycosylated IgE-ICs induced a significantly higher anti-IgE IgG response and more IgG-secreting plasma cells than deglycosylated IgE-ICs. Passive immunization of IgE-sensitized mice with purified anti-IgE IgG increased the clearance of IgE and prevented systemic anaphylaxis upon allergen challenge. Anti-IgE IgG purified from the serum of mice immunized with deglycosylated IgE-ICs, led to a significantly reduced elimination and protection, confirming that the IgE glycans themselves are the primary drivers of the protectivity induced by the IgE-immune complexes. CONCLUSION IgE glycosylation is essential for a robust anti-IgE IgG response and might be an important regulator of serum IgE levels

Model sensitivity in the effect of Antarctic sea ice and stratification on atmospheric pCO2

Several recent papers have demonstrated a decrease in atmospheric pCO2 resulting from barriers to communication between the deep sea and the atmosphere in the Southern Ocean. Stephens and Keeling [2000] decreased pCO2 by increasing Antarctic sea ice in a seven-box model of the world ocean, and Toggweiler [1999] showed a similar response to Southern Ocean stratification. In box models the pCO2 of the atmosphere is controlled by the region of the surface ocean that fills the deep sea [Archer et al., 2000a]. By severing the Southern Ocean link between the deep sea and the atmosphere, atmospheric pCO2 in these models is controlled elsewhere and typically declines, although the models range widely in their responses. “Continuum models,” such as three-dimensional (3-D) and 2-D general circulation models, control pCO2 in a more distributed way and do not exhibit box model sensitivity to high-latitude sea ice or presumably stratification. There is still uncertainty about the high-latitude sensitivity of the real ocean. Until these model sensitivities can be resolved, glacial pCO2 hypotheses and interpretations based on Southern Ocean barrier mechanisms (see above mentioned references plus Elderfield and Rickaby [2000], Francois et al. [1998], Gildor and Tziperman [2001], Sigman and Boyle [2000], and Watson et al. [2000]) are walking on thin ice

IgE glycans promote anti-IgE IgG autoantibodies that facilitate IgE serum clearance via Fc Receptors

BackgroundRecent studies have shown that IgE glycosylation significantly impacts the ability of IgE to bind to its high-affinity receptor FcεRI and exert effector functions. We have recently demonstrated that immunizing mice with IgE in a complex with an allergen leads to a protective, glycan-dependent anti-IgE response. However, to what extent the glycans on IgE determine the induction of those antibodies and how they facilitate serum clearance is unclear.Therefore, we investigated the role of glycan-specific anti-IgE IgG autoantibodies in regulating serum IgE levels and preventing systemic anaphylaxis by passive immunization.MethodsMice were immunized using glycosylated or deglycosylated IgE-allergen-immune complexes (ICs) to induce anti-IgE IgG antibodies. The anti-IgE IgG antibodies were purified and used for passive immunization.ResultsGlycosylated IgE-ICs induced a significantly higher anti-IgE IgG response and more IgG-secreting plasma cells than deglycosylated IgE-ICs. Passive immunization of IgE-sensitized mice with purified anti-IgE IgG increased the clearance of IgE and prevented systemic anaphylaxis upon allergen challenge. Anti-IgE IgG purified from the serum of mice immunized with deglycosylated IgE-ICs, led to a significantly reduced elimination and protection, confirming that the IgE glycans themselves are the primary drivers of the protectivity induced by the IgE-immune complexes.ConclusionIgE glycosylation is essential for a robust anti-IgE IgG response and might be an important regulator of serum IgE levels

Glycan-specific IgG anti-IgE autoantibodies are protective against allergic anaphylaxis in a murine model.

BACKGROUND IgE causes anaphylaxis in type-1 hypersensitivity diseases by activating degranulation of effector cells such as mast cells and basophils. The mechanisms that control IgE activity and prevent anaphylaxis under normal conditions are still enigmatic. OBJECTIVE We aimed to unravel how anti-IgE autoantibodies are induced and understand their role in regulating serum IgE level and allergic anaphylaxis. METHODS We immunized mice with different forms of IgE and tested anti-IgE autoantibody responses and their specificities. We then analysed the effect of those antibodies on serum kinetics and their in vitro and in vivo impact on anaphylaxis. Finally, we investigated anti-IgE autoantibodies in human sera. RESULTS Immunization of mice with IgE-immune complexes induced glycan-specific anti-IgE autoantibodies. The anti-IgE autoantibodies prevented effector cell sensitization, reduced total IgE serum levels, protected mice from passive and active IgE sensitization, and resulted in cross-protection against different allergens. Furthermore, glycan-specific anti-IgE autoantibodies were present in sera from allergic and non-allergic subjects. CONCLUSION In conclusion, we provide first evidence that in the murine model the serum level and anaphylactic activity of IgE may be down-regulated by glycan-specific IgG anti-IgE autoantibodies

La pandémie a besoin d'une stratégie cantonale et supracantonale : changement de perspective après deux ans de gestion du Covid-19 = Zeit für eine kantonale und überkantonale Corona-Strategie : Perspektivenwechsel nach zwei Jahren Corona-Politik

Das Ende der Corona-Pandemie für die Schweiz zeichnet sich ab. Damit wird sich die Gesundheitspolitik wieder auf ihre Regelstrukturen abstützen und sich statt nur auf die Kapazität der Intensivpflegestationen wieder auf umfassendere Ziele ausrichten können. Eine besondere Bedeutung werden dabei kantonale und überkantonale Corona-Strategien erlangen. = La fin de la pandémie de coronavirus se dessine en Suisse. Ainsi, la politique de la santé pourra s’appuyer à nouveau sur ses structures ordinaires et se recentrer sur des objectifs plus larges que la seule capacité des unités de soins intensifs. Les stratégies cantonales et supracantonales en matière de coronavirus revêtiront une importance particulière