Accumulated immune complexes of IgE and omalizumab trap allergens in an in vitro model

Hsu, Chuan-Long; Shiung, Yu-Yu; Lin, Bai-Ling; Chang, Hwan‐You; Chang, Tse Wen

doi:10.1016/j.intimp.2010.02.001

Cited by 18 publications

(8 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…All patients showed an 1.2‐ to 11‐fold increase of total serum IgE as determined by using two independent detection systems indicating the well‐known development of IgE‐omalizumab complexes (Fig. d,e; P < 0.05), which results in enhanced serum IgE concentrations due to an extended half‐life of complexed IgE . It has been speculated that serum IgE measured by ADVIA Centaur would quantify free IgE in an indirect fashion due to competing epitopes for the detection antibodies and omalizumab .…”

Section: Resultsmentioning

confidence: 92%

“…1d,e; P < 0.05), which results in enhanced serum IgE concentrations due to an extended half-life of complexed IgE. 32,33 It has been speculated that serum IgE measured by ADVIA Centaur would quantify free IgE in an indirect fashion due to competing epitopes for the detection antibodies and omalizumab. 34 However, we found a strong correlation of total IgE measured by ADVIA Centaur and ImmunoCAP (r = À0.9700, P < 0.0001, data not shown).…”

Section: Csu Patients Show a Differentiated Clinical Response To Antimentioning

confidence: 99%

See 1 more Smart Citation

Omalizumab response correlates with reduced IFN‐γ‐, IL‐10‐ and IL‐31‐secreting cells in chronic spontaneous urticaria

Rauber

Pickert²,

Holiangu³

et al. 2020

Acad Dermatol Venereol

View full text Add to dashboard Cite

Background The anti‐IgE antibody omalizumab has been approved for the treatment of chronic spontaneous urticaria (CSU) in patients insufficiently responding to antihistamines. However, its mode of action in CSU is not clearly understood. Objectives The aim of this study was to get a better insight in the immune mechanisms involved in clinical improvement of CSU patients treated with omalizumab. Methods Chronic spontaneous urticaria patients (n = 15) were followed for 5 months after initiation of omalizumab treatment. Clinical symptoms were assessed by UCT and CU‐Q2oL. Cell‐bound IgE was quantified on both FcεRI‐ and FcεRII‐expressing cell populations in peripheral blood. In addition, IgE and IgG as well as their receptors were measured on basophils, and basophil activation was assessed with different concentrations of anti‐FcεRI and fMLP. Furthermore, the frequencies of different T‐cell subsets secreting IL‐5, IL‐10, IL‐31 or IFN‐γ were analysed by ELISpot assay. Results Seven patients showed a full, five a partial and three no clinical response to omalizumab. Cell‐bound IgE was reduced on FcεRI‐bearing cells, but not on FcεRII‐expressing cells. Likewise, the expression of FcεRI declined. Basophil activation increased upon FcεRI‐stimulation while their sensitivity was not affected. Both basophil and T‐cell frequencies remained unchanged. However, when comparing the individual response to omalizumab treatment with distinct T‐cell subsets, a significant correlation was found between improved UCT and decreased frequencies of IL‐10‐, IL‐31‐ and IFN‐γ‐secreting T cells. Conclusions We here show that besides addressing IgE‐dependent immune mechanisms, omalizumab treatment of CSU patients has effects on distinct T‐cell subsets, which correlate with clinical improvement.

show abstract

Section: Resultsmentioning

confidence: 92%

Section: Csu Patients Show a Differentiated Clinical Response To Antimentioning

confidence: 99%

Omalizumab response correlates with reduced IFN‐γ‐, IL‐10‐ and IL‐31‐secreting cells in chronic spontaneous urticaria

Rauber

Pickert²,

Holiangu³

et al. 2020

Acad Dermatol Venereol

View full text Add to dashboard Cite

show abstract

“…The goat polyclonal anti-human IgE and the myeloma IgE (JK) were provided by Dr. Robert Hamilton, JHU. The SE44 IgE, which recognized a synthetic 15 amino acid peptide (R15K) has been described elsewhere ( 19 ) and was provided by Dr. Donald MacGlashan, Jr., JHU.…”

Section: Methodsmentioning

confidence: 99%

Epithelial Cell-Associated Galectin-3 Activates Human Dendritic Cell Subtypes for Pro-Inflammatory Cytokines

2020

View full text Add to dashboard Cite

There is mounting evidence that galectin-3 is a prognostic and diagnostic biomarker associated with diverse diseases and conditions, including cancer, cardiovascular disease, autoimmunity, wound healing, allergic disease, and chronic inflammation in general. Yet, whether and exactly how galectin-3 may participate in the pathogenesis of these diseases remains poorly understood. Recently, we have linked the expression of galectin-3 on the A549 epithelial cell line –an adenocarcinoma, to the activation of human basophils for the release of histamine and secretion of IL-4 and IL-13. These responses proved dependent on cell-to-cell contact, basophil expression of IgE, were inhibited by n-acetyllactosamine, and were ablated when basophils were co-cultured with A549 clones lacking galectin-3 expression. While recombinant galectin-3 failed to activate basophils when in solution, microspheres expressing this lectin did so by mimicking the responses seen when using A549 cells. Given the IgE dependency of the basophil responses, and the fact that galectin-3 is long known to bind this immunoglobulin, we hypothesize that a similar mode of activation extends to other IgE-bearing cells. To investigate this possibility, we tested epithelial cell-associated galectin-3 for its capacity to activate human dendritic cells, including the plasmacytoid and myeloid subtypes as well as monocytes, all of which bind IgE. Indeed, results indicate that epithelial cell-associated galectin-3 activated these cells for robust production of TNF-α and IL-6 and up-regulated the expression of activation markers found on dendritic cells. Moreover, many of the same parameters previously observed for basophils applied to the findings herein, including evidence that matrix-bound galectin-3 (whether on epithelial cells or microspheres) facilitates this mode of activation. In contrast, IgE expression was dispensable for these galectin-3-dependent cytokine responses, implying that this lectin activates dendritic cells (and monocytes) by binding to a glycoprotein other than this immunoglobulin. Overall, these findings further demonstrate how galectin-3 mediates immune cell activation, providing novel insight into how this lectin may promote chronic inflammation underlying the pathogenesis of many diseases.

show abstract

“…During the formation of omalizumab-IgE heterodimers in the serum, 42 the monoclonal IgG 1 -anti-Cε3(IgE) complex, can be recognized by FcγRs in immune and dendritic cells and removed from systemic circulation. 43 This evidence suggests that omalizumab may interact with basophil FcγRs and regulate cell response to surface IgE-FcεRI complexes. Although basophil response to further allergens during anti-IgE immunotherapy has not been yet investigated, the accepted model suggests that clearance of allergens by immunocomplexes (ICs)-mediated competition or trap mechanism, elicits also a downregulation mechanism of FcεRI on basophil membrane, then reducing basophil IgE-mediated response and allergy symptoms.…”

Section: Role Of Basophils In Immune System Following Immunotherapy: mentioning

confidence: 99%

Immunotherapy in allergy and cellular tests

Chirumbolo

2014

Human Vaccines & Immunotherapeutics

View full text Add to dashboard Cite

Accumulated immune complexes of IgE and omalizumab trap allergens in an in vitro model

Cited by 18 publications

References 31 publications

Omalizumab response correlates with reduced IFN‐γ‐, IL‐10‐ and IL‐31‐secreting cells in chronic spontaneous urticaria

Omalizumab response correlates with reduced IFN‐γ‐, IL‐10‐ and IL‐31‐secreting cells in chronic spontaneous urticaria

Epithelial Cell-Associated Galectin-3 Activates Human Dendritic Cell Subtypes for Pro-Inflammatory Cytokines

Immunotherapy in allergy and cellular tests

Contact Info

Product

Resources

About