The anti-inflammatory effects of omalizumab confirm the central role of IgE in allergic inflammation

Holgate, Stephen T.; Casale, Thomas B.; Wenzel, Sally E.; Bousquet, Jean; Deniz, Yamo; Reisner, Colin

doi:10.1016/j.jaci.2004.11.053

Cited by 411 publications

(305 citation statements)

References 39 publications

(51 reference statements)

Supporting

Mentioning

283

Contrasting

Unclassified

Order By: Relevance

“…[1][2][3][4][5]7,8,22 Our results show that most of the severe hypersensitivity reactions to cetuximab in the subjects we studied were associated with IgE antibodies against galactose-α-1,3-galactose that were present before treatment with cetuximab. The assay we used identified 17 of the 21 subjects whose treatment had to be discontinued after the first infusion because of a hypersensitivity reaction.…”

Section: Discussionmentioning

confidence: 55%

Cetuximab-Induced Anaphylaxis and IgE Specific for Galactose-α-1,3-Galactose

Chung¹,

Mirakhur

Chan³

et al. 2008

N Engl J Med

1,342

1,079

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 55%

Cetuximab-Induced Anaphylaxis and IgE Specific for Galactose-α-1,3-Galactose

Chung¹,

Mirakhur

Chan³

et al. 2008

N Engl J Med

1,342

1,079

View full text Add to dashboard Cite

show abstract

“…Additionally, IgE has the capacity to induce the production of Th2-type cytokines and the development of airway inflammation and AHR in mice (9)(10)(11), indicating the importance of IgE in chronic asthmatic responses. More interestingly, in clinical studies, the severity of symptoms in some poorly controlled asthmatic patients was improved by treatment with a humanized anti-IgE Ab (12)(13)(14). Thus, allergen-specific IgE can be indispensable for the chronic pathogenesis of asthma, creating a vicious cycle in asthmatic patients.…”

mentioning

confidence: 99%

Complement C3a-Induced IL-17 Plays a Critical Role in an IgE-Mediated Late-Phase Asthmatic Response and Airway Hyperresponsiveness via Neutrophilic Inflammation in Mice

Mizutani

Goshima

Nabe

et al. 2012

The Journal of Immunology

View full text Add to dashboard Cite

Allergen-specific IgE plays an essential role in the pathogenesis of allergic asthma. Although there has been increasing evidence suggesting the involvement of IL-17 in the disease, the relationship between IL-17 and IgE-mediated asthmatic responses has not yet been defined. In this study, we attempted to elucidate the contribution of IL-17 to an IgE-mediated late-phase asthmatic response and airway hyperresponsiveness (AHR). BALB/c mice passively sensitized with an OVA-specific IgE mAb were challenged with OVA intratracheally four times. The fourth challenge caused a late-phase increase in airway resistance associated with elevated levels of IL-17+CD4+ cells in the lungs. Multiple treatments with a C3a receptor antagonist or anti-C3a mAb during the challenges inhibited the increase in IL-17+CD4+ cells. Meanwhile, a single treatment with the antagonist or the mAb at the fourth challenge suppressed the late-phase increase in airway resistance, AHR, and infiltration by neutrophils in bronchoalveolar lavage fluid. Because IL-17 production in the lungs was significantly repressed by both treatments, the effect of an anti–IL-17 mAb was examined. The late-phase increase in airway resistance, AHR, and infiltration by neutrophils in bronchoalveolar lavage fluid was inhibited. Furthermore, an anti–Gr-1 mAb had a similar effect. Collectively, we found that IgE mediated the increase of IL-17+CD4+ cells in the lungs caused by repeated Ag challenges via C3a. The mechanisms leading to the IgE-mediated late-phase asthmatic response and AHR are closely associated with neutrophilic inflammation through the production of IL-17 induced by C3a.

show abstract

“…After this, the late phase reaction result in chronic and persistent obstruction by a severe eosinophilic infl ammation in the lung. Elevated serum and BAL fl uid IgE levels have been reported to be important in the development of asthmatic responses in human and OVA challenges induced more signifi cant increase in the total serum IgE and BAL fl uid IgE than asthmatic patients (Hamelmann et al, 1999;Holgate et al, 2005). Moreover, the Th2 cytokines, IL-4 and IL-5, were considered to associate with infl ammatory cell infi ltration and mucus hypersecretion and to regulate immune functions in mice (Steinke, 2004).…”

Section: Discussionmentioning

confidence: 99%