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41 results on '"Iweala, Onyinye I."'

5. Anaphylaxis

Author

LoVerde, Daniel, Iweala, Onyinye I., Eginli, Ariana, and Krishnaswamy, Guha

Published
2018
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9. Antitussive Use in Patients with Inadequately Controlled Moderate-to-Severe Asthma: A Post Hoc Analysis of the Omalizumab EXTRA Trial

Author

Rutland,Cedric J, Iweala,Onyinye I, Anders,Kyle, Ko,Jinnie, Mital,Parul, Gupta,Sachin, Mohan,Arjun, Rutland,Cedric J, Iweala,Onyinye I, Anders,Kyle, Ko,Jinnie, Mital,Parul, Gupta,Sachin, and Mohan,Arjun

Abstract

Cedric J Rutland,1 Onyinye I Iweala,2 Kyle Anders,3 Jinnie Ko,3 Parul Mital,3 Sachin Gupta,3 Arjun Mohan4 1Rutland Medical Group, Newport Beach, CA, USA; 2Division of Rheumatology, Allergy, and Immunology, University of North Carolina, Chapel Hill, NC, USA; 3Genentech, Inc., South San Francisco, CA, USA; 4Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, MI, USACorrespondence: Sachin Gupta, Genentech, Inc., 1 DNA Way, South San Francisco, CA, 94080, USA, Tel +1 650-763-7791, Email Guptas71@gene.comAbstract: Acute and chronic cough are common symptoms in patients with severe allergic asthma. Although asthma-related cough can be controlled by asthma-specific medications, both prescription and over-the-counter antitussives are often also necessary. The anti-immunoglobulin E monoclonal antibody omalizumab is an effective treatment for patients with moderate-to-severe asthma, but little is known about subsequent antitussive use patterns. This post hoc analysis examined data from the Phase 3 EXTRA study that included patients aged 12– 75 years with inadequately controlled moderate-to-severe asthma. Baseline antitussive use was low overall (16/427, 3.7% for omalizumab and 18/421, 4.3% for placebo). Among patients with no baseline antitussive use (n = 411 omalizumab, n = 403 placebo), most patients (88.3% omalizumab, 83.4% placebo) reported not using antitussives during the 48-week treatment period. The percentage of patients using 1 antitussive was lower for patients treated with omalizumab than placebo (7.1% vs 13.2%), although the adjusted rate of antitussive use during the treatment period was similar for omalizumab and placebo (0.22 and 0.25). Non-narcotics were used more often than narcotics. In conclusion, this analysis found low use of antitussives in patients with severe asthma and suggests that omalizumab may have the potential to decrease antitussive use.Keywords: antitussive, asthma, cough, omalizumab

Published
2023

16. Novel peanut-specific human IgE monoclonal antibodies enable screens for inhibitors of the effector phase in food allergy

Author

Guo, Rishu, Burks, A. Wesley, Kulis, Michael D., Suber, Jada, Zhang, Yugen, Iweala, Onyinye I., Smith, Scott A., and Ye, Ping

Subjects
Sialic Acid Binding Immunoglobulin-like Lectins, Arachis, Receptors, IgE, Immunology, Antibodies, Monoclonal, Allergens, Immunoglobulin E, Cell Degranulation, beta-N-Acetylhexosaminidases, Rats, Immunology and Allergy, Animals, Cytokines, Humans, Peanut Hypersensitivity, Food Hypersensitivity
Abstract

Background10% of US residents have food allergies, including 2% with peanut allergy. Mast cell mediators released during the allergy effector phase drive allergic reactions. Therefore, targeting sensitized mast cells may prevent food allergy symptoms.ObjectiveWe used novel, human, allergen-specific, IgE monoclonal antibodies (mAbs) created using human hybridoma techniques to design anin vitrosystem to evaluate potential therapeutics targeting sensitized effector cells.MethodsTwo human IgE mAbs specific for peanut, generated through human hybridoma techniques, were used to sensitize rat basophilic leukemia (RBL) SX-38 cells expressing the human IgE receptor (FcϵRI). Beta-hexosaminidase release (a marker of degranulation), cytokine production, and phosphorylation of signal transduction proteins downstream of FcϵRI were measured after stimulation with peanut. Degranulation was also measured after engaging inhibitory receptors CD300a and Siglec-8.ResultsPeanut-specific human IgE mAbs bound FcϵRI, triggering degranulation after stimulation with peanut in RBL SX-38 cells. Sensitized RBL SX-38 cells stimulated with peanut increased levels of phosphorylated SYK and ERK, signal transduction proteins downstream of FcϵRI. Engaging inhibitory cell surface receptors CD300a or Siglec-8 blunted peanut-specific activation.ConclusionAllergen-specific human IgE mAbs, expressed from human hybridomas and specific for a clinically relevant food allergen, passively sensitize allergy effector cells central to thein vitromodels of the effector phase of food allergy. Peanut reproducibly activates and induces degranulation of RBL SX-38 cells sensitized with peanut-specific human IgE mAbs. This system provides a unique screening tool to assess the efficacy of therapeutics that target allergy effector cells and inhibit food allergen-induced effector cell activation.

Published
2022

18. Toll-Like Receptor 4-Mediated Regulation of Spontaneous Helicobacter-Dependent Colitis in IL-10–Deficient Mice

Author

Matharu, Kabir S., Mizoguchi, Emiko, Cotoner, Carmen Alonso, Nguyen, Deanna D., Mingle, Bethany, Iweala, Onyinye I., McBee, Megan E., Stefka, Andrew T., Prioult, Guenolee, Haigis, Kevin M., Bhan, Atul K., Snapper, Scott B., Murakami, Hidehiro, Schauer, David B., Reinecker, Hans–Christian, Mizoguchi, Atsushi, and Nagler, Cathryn R.

Published
2009
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32. Epigenetic Dysfunction in T cells is Associated with Enhanced Type-2 and Blunted Regulatory Immunity

Author

Iweala, Onyinye I., primary, Hardy, Lakeya C., additional, Choudhary, Shailesh, additional, Wang, Hsing-Hui, additional, Addison, Claire T., additional, Milind, Nikhil, additional, Orgel, Kelly A., additional, Kulis, Michael D., additional, Urban, Joseph F., additional, Nagler, Cathryn R., additional, Burks, A. Wesley, additional, Su, Maureen A., additional, and Commins, Scott P., additional

Published
2019
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35. Vaccine-Induced Antibody Isotypes Are Skewed by Impaired CD4 T Cell and Invariant NKT Cell Effector Responses in MyD88-Deficient Mice1

Author

Iweala, Onyinye I., Smith, Donald W., Matharu, Kabir S., Sada-Ovalle, Isabel, Nguyen, Deanna D., DeKruyff, Rosemarie H., Umetsu, Dale T., Behar, Samuel M., and Nagler, Cathryn R.

Subjects
CD4-Positive T-Lymphocytes, Male, Mice, Knockout, Vaccines, Synthetic, Salmonella Vaccines, Injections, Subcutaneous, Toll-Like Receptors, Administration, Oral, hemic and immune systems, Mice, Transgenic, Vaccines, Attenuated, Antibodies, Bacterial, Article, Immunoglobulin Isotypes, Mice, Inbred C57BL, Mice, Myeloid Differentiation Factor 88, Animals, Natural Killer T-Cells, Female, Injections, Intraperitoneal
Abstract

The requirement for TLR signaling in the initiation of an Ag-specific Ab response is controversial. In this report we show that a novel OVA-expressing recombinant Salmonella vaccine (Salmonella-OVA) elicits a Th1-biased cell-mediated and serum Ab response upon oral or i.p. immunization of C57BL/6 mice. In MyD88(-/-) mice, Th1-dependent Ab responses are greatly reduced while Th2-dependent Ab isotypes are elevated in response to oral and i.p., but not s.c. footpad, immunization. When the T effector response to oral vaccination is examined we find that activated, adoptively transferred Ag-specific CD4(+) T cells accumulate in the draining lymph nodes, but fail to produce IFN-gamma, in MyD88(-/-) mice. Moreover, CD1d tetramer staining shows that invariant NKT cells are activated in response to oral Salmonella-OVA vaccination in wild-type, but not MyD88(-/-), mice. Treatment with neutralizing Ab to CD1d reduces the OVA-specific Ab response only in MyD88-sufficient wild-type mice, suggesting that both Ag-specific CD4 T cell and invariant NKT cell effector responses to Salmonella-OVA vaccination are MyD88 dependent. Taken together, our data indicate that the type of adaptive immune response generated to this live attenuated vaccine is regulated by both the presence of MyD88-mediated signals and vaccination route, which may have important implications for future vaccine design.

Published
2009

37. W1627 TLR4 Mediated Regulation of Spontaneous Colitis in IL-10 Deficient Mice

Author

Matharu, Kabir S., primary, Mizoguchi, Emiko, additional, Cotoner, Carmen Alonso, additional, Nguyen, Deanna D., additional, Mingle, Bethany, additional, Iweala, Onyinye I., additional, McBee, Megan E., additional, Stefka, Andrew, additional, Prioult, Guenolee, additional, Haigis, Kevin, additional, Bhan, Atul K., additional, Snapper, Scott B., additional, Murakami, Hidehiro, additional, Schauer, David, additional, Reinecker, Hans-Christian, additional, Mizoguchi, Atsushi, additional, and Nagler, Cathryn R., additional

Published
2009
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40. Intestinal Helminth Infection Impairs Oral and Parenteral Vaccine Efficacy.

Author

Zhang Y, Hardy LC, Kapita CM, Hall JA, Arbeeva L, Campbell E, Urban JF, Belkaid Y, Nagler CR, and Iweala OI

Subjects
Mice, Animals, Vaccine Efficacy, CD4-Positive T-Lymphocytes, Vaccines, Synthetic, Ovalbumin, Mice, Inbred BALB C, Helminthiasis, Intestinal Diseases, Parasitic
Abstract

The impact of endemic parasitic infection on vaccine efficacy is an important consideration for vaccine development and deployment. We have examined whether intestinal infection with the natural murine helminth Heligmosomoides polygyrus bakeri alters Ag-specific Ab and cellular immune responses to oral and parenteral vaccination in mice. Oral vaccination of mice with a clinically relevant, live, attenuated, recombinant Salmonella vaccine expressing chicken egg OVA (Salmonella-OVA) induced the accumulation of activated, OVA-specific T effector cells rather than OVA-specific regulatory T cells in the GALT. Intestinal helminth infection significantly reduced Th1-skewed Ab responses to oral vaccination with Salmonella-OVA. Activated, adoptively transferred, OVA-specific CD4+ T cells accumulated in draining mesenteric lymph nodes of vaccinated mice, regardless of their helminth infection status. However, helminth infection increased the frequencies of adoptively transferred OVA-specific CD4+ T cells producing IL-4 and IL-10 in the mesenteric lymph node. Ab responses to the oral Salmonella-OVA vaccine were reduced in helminth-free mice adoptively transferred with OVA-specific CD4+ T cells harvested from mice with intestinal helminth infection. Intestinal helminth infection also significantly reduced Th2-skewed Ab responses to parenteral vaccination with OVA adsorbed to alum. These findings suggest that vaccine-specific CD4+ T cells induced in the context of helminth infection retain durable immunomodulatory properties and may promote blunted Ab responses to vaccination. They also underscore the potential need to treat parasitic infection before mass vaccination campaigns in helminth-endemic areas., (Copyright © 2023 by The American Association of Immunologists, Inc.)

Published
2023
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41. Strategies for Mast Cell Inhibition in Food Allergy.

Author

Suber J and Iweala OI

Subjects
Humans, Receptors, IgE, Signal Transduction, Food Hypersensitivity, Mast Cells
Abstract

Mast cells are tissue resident allergic effector cells that drive IgE-mediated food allergies. There are several steps leading to mast cell activation in the context of allergic disease that can be targeted to prevent mast cell activation and degranulation. These include blocking IgE-FcεRI crosslinking and type 2 cytokine receptor activation; modulating cell-surface neural chemical receptors; stabilizing mast cell membranes to prevent co-localization of activating receptors; impeding intracellular signaling; and engaging cell surface inhibitory receptors. This review highlights several ITIM-containing inhibitory mast cell surface receptors that could serve as pharmaceutical targets to prevent mast cell activation and degranulation in the context of food allergy. When activated, these ITIM-containing inhibitory receptors recruit the phosphatases SHP-1, SHP-2, and/or SHIP to dephosphorylate the tyrosine kinases responsible for activation signals downstream of the IgE-FcεRI complex. We describe several members of the Ig and Ig-like inhibitory receptor and C-type lectin inhibitory receptor superfamilies. Fundamental studies exploring the behavior of these receptors within the context of experimental food allergy models are needed. A deeper understanding of how these receptors modulate mast cell-driven food allergic responses will shape future strategies to harness these inhibitory receptors to treat food allergy., (Copyright ©2020, Yale Journal of Biology and Medicine.)

Published
2020

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