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http://hdl.handle.net/11375/29107
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DC Field | Value | Language |
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dc.contributor.advisor | Mukherjee, Manali | - |
dc.contributor.author | Miyasaki, Kate | - |
dc.date.accessioned | 2023-10-24T16:12:03Z | - |
dc.date.available | 2023-10-24T16:12:03Z | - |
dc.date.issued | 2023 | - |
dc.identifier.uri | http://hdl.handle.net/11375/29107 | - |
dc.description.abstract | Asthma is a common chronic respiratory disease where patients suffer from restricted airways and airway inflammation (mainly eosinophilic type 2 (T2) inflammation). Inhaled (ICS)/oral corticosteroids (OCS) and, more recently T2-targeting biologics, are prescribed as mainstay therapies for asthma. Despite these therapies, a subset of asthma patients continues to have symptoms and airway inflammation, suggesting an underlying additional asthma pathology. We have observed multiple airway autoantibodies in 55% of moderate-to-severe asthma patients associated with inadequate response to corticosteroids and anti-T2 biologics. Increased airway degranulation (eosinophilic and/or infective) together with lymphopenia (low lymphocyte counts) underlie these self-reactive/autoimmune-like events. In healthy individuals, regulatory lymphocytes limit the development and activity of self-reactive cells, including those capable of producing autoantibodies. Lymphopenia can lead to skewed non-regulatory to regulatory lymphocyte subsets that support a microenvironment with reduced ability to limit self-reactivity. In this study, wanted to measure B cell subsets by flow cytometry and non-regulatory to regulatory B cell ratios in asthma patients and healthy controls. To understand B cell compartmentalization, we analyzed peripheral and sputum B cells. We identified decreased regulatory B cells (Bregs), in particular CD5+ Bregs, and skewed non-regulatory to regulatory B cell ratios in both circulation and airways of asthma patients. Compared to healthy controls, only patients requiring daily OCS had significantly lower CD5+ Bregs, suggesting a reduced regulatory component in more severe patients. Further, CD5+ Bregs, capable of producing immunomodulatory interleukin-10, were significantly lower in patients with a history of multiple lymphopenic events (70% requiring daily OCS). Together, this supports the need to investigate lymphopenia-induced dysregulation of Bregs, increase in autoreactive B cells and airway autoreactivities, and subsequent progression into a more-severe therapy refractory autoimmune pathology. This opens a new avenue for asthma treatment, particularly for the severe population with airway autoimmune responses often not targeted/controlled by current anti-inflammatory therapies. | en_US |
dc.language.iso | en | en_US |
dc.subject | asthma | en_US |
dc.subject | autoimmunity | en_US |
dc.subject | B cells | en_US |
dc.subject | lymphopenia | en_US |
dc.title | Decreased regulatory B cells in asthma associated with severity | en_US |
dc.title.alternative | Peripheral and airway B cells in asthma | en_US |
dc.type | Thesis | en_US |
dc.contributor.department | Biochemistry and Biomedical Sciences | en_US |
dc.description.degreetype | Thesis | en_US |
dc.description.degree | Master of Science (MSc) | en_US |
dc.description.layabstract | Asthma is a common respiratory disease where patients have difficulty breathing and airway inflammation. Corticosteroids and/or targeting biologic therapies are prescribed to reduce inflammation. Despite these treatments, some patients still have inflammation. In patients that don’t respond well to treatment, we have found evidence of self-attacking antibodies that can further lead to disease severity. These antibodies are produced by self-attacking B cells normally suppressed by regulatory B cells (Bregs). We wanted to measure if asthma patients have reduced ability to limit self-attacking B cells because of reduced Bregs. We found that asthma patients have lower Bregs and an imbalance of non-regulatory to regulatory B cells in the blood and airways. Together, we show B cell subsets that suggest a self-attacking asthma component, not targeted by current asthma treatments. Understanding the involvement of Bregs in asthma opens a new therapeutic option in those that don’t respond well to current treatment. | en_US |
Appears in Collections: | Open Access Dissertations and Theses |
Files in This Item:
File | Description | Size | Format | |
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Miyasaki_Kate_HG_2023Sep_MSc.pdf | 4.7 MB | Adobe PDF | View/Open |
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