Obesity Accelerates Age Defects in Mouse and Human B Cells

Frasca, Daniela; Blomberg, Bonnie B.

doi:10.3389/fimmu.2020.02060

Cited by 17 publications

(11 citation statements)

References 80 publications

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“…These findings indicate that the adaptive B cell responses to mRNA vaccine are severely weakened in DIO mice, which may be due to impairments in B cell development, activation, and functions. 64 , 65 , 66 Interestingly, vaccination offered a certain degree of protection to Omicron BA.1-challenged DIO mice in the lower respiratory but not in the nasal turbinates of infected animals. The insufficient protection in the nasal turbinate tissues may be due to insufficient mucosal immune responses upon intra-muscular vaccination that failed to evoke sufficient protective immunity at the mucosal sites.…”

Section: Discussionmentioning

confidence: 96%

COVID-19 mRNA vaccine protects against SARS-CoV-2 Omicron BA.1 infection in diet-induced obese mice through boosting host innate antiviral responses

Chen¹,

Song²,

Li³

et al. 2023

eBioMedicine

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Section: Discussionmentioning

confidence: 96%

COVID-19 mRNA vaccine protects against SARS-CoV-2 Omicron BA.1 infection in diet-induced obese mice through boosting host innate antiviral responses

Chen¹,

Song²,

Li³

et al. 2023

eBioMedicine

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“…Obesity promotes inflammation and induces metabolic and functional changes in immune cells by altering humoral immunity and reducing the antibody response to vaccine immunization or viral infection. 17 , 18 Obesity-associated dysregulation of the immune system may negatively affect IgG production in patients treated with RTX.…”

Section: Discussionmentioning

confidence: 99%

Rituximab-Induced Hypogammaglobulinemia and Risk of Infection in Neuromyelitis Optica Spectrum Disorders

Kim

Park

Kim

et al. 2022

Neurol Neuroimmunol Neuroinflamm

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Background and ObjectivesTo investigate the frequency and predictors of hypogammaglobulinemia during long-term rituximab (RTX) treatment in patients with neuromyelitis optica spectrum disorder (NMOSD) and its association with infections.MethodsWe retrospectively reviewed the data of patients with NMOSD who received RTX through the maintenance regimen based on memory B-cell detection for at least 1 year from 2006 to 2021 at an institutional referral center for NMOSD.ResultsA total of 169 patients received a median of 10 courses (range 1–27) of RTX reinfusion after induction over a median of 8 (range, 1–15) years. Their mean serum immunoglobulin (Ig)G level began to decline significantly after 2 years of treatment, steadily declined at a rate of 2%–8% per year for the following 8 years, and then plateaued after 10 years. The proportion of patients with hypo-IgG (<6 g/L) increased from 1.2% after 1 year of treatment to 41% after 14 years of treatment. While being treated with RTX, 58 (34%) patients had 114 infections, of whom 14 (8%) patients had 15 severe infections. Multivariable logistic regression analyses identified duration of RTX treatment in years (odds ratio [OR] 1.234, 95% confidence interval [CI] 1.015–1.502), mean annual RTX dose (OR 0.063, 95% CI 0.009–0.434), history of mitoxantrone (OR 3.318, 95% CI 1.109–9.93), hypo-IgG at baseline (OR 40.552, 95% CI 3.024–543.786), and body mass index >25 kg/m2 (OR 4.798, 95% CI 1.468–15.678) as independent predictors of hypo-IgG. The risk of infection during RTX treatment was independently associated with high Expanded Disability Status Scale scores (OR 1.427, 95% CI 1.2–1.697) and relapses during RTX treatment (OR 1.665, 95% CI 1.112–2.492), but not with hypogammaglobulinemia.DiscussionOver 14 years of long-term RTX treatment, IgG levels gradually decreased, and the frequency of hypo-IgG increased to 41% of the patients. Patients with prolonged memory B-cell depletion after RTX, previous mitoxantrone history, hypo-IgG at baseline, or obesity were at risk of developing RTX-induced hypogammaglobulinemia. Nevertheless, infection rates remained low during treatment, and reduced immunoglobulin levels were not associated with an increased incidence of infections.

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“…This pro-inflammatory environment may lead to a shift in immune cell composition and immune function in morbidly obese patients as compared to lean individuals ( 8 , 9 ). Morbid obesity has been shown to decrease B cell function in humans, impairs B cell responses to infections and vaccines ( 10 , 11 ) and leads to loss of T cell regulatory mechanisms ( 12 ). Also, presence of epithelial signals regulating the adipose tissue immunity may be altered in morbidly obese individuals ( 13 ).…”

Section: Introductionmentioning

confidence: 99%

T and B Cell Composition and Cytokine Producing Capacity Before and After Bariatric Surgery

et al. 2022

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Morbid obesity is associated with a chronic state of low-grade inflammation, which may lead to accelerated differentiation of T and B cells. These differentiated immune cells are strongly cytotoxic and have an increased pro-inflammatory cytokine producing capacity. Furthermore, the anti-inflammatory function of the T and B cells decreases. The aim of this study was to evaluate the effect of morbid obesity on the subset profile and cytokine producing capacity of T and B cells. Subsequently, we assessed whether bariatric surgery affected the subset profile and cytokine producing capacity of these cells. We determined the proportion of T and B cell subsets and their cytokine producing capacity in peripheral blood collected from 23 morbidly obese patients before and three months after bariatric surgery using flow-cytometry. We compared this with the results of 25 lean controls. Both CD4+ and CD8+ T cells showed a more differentiated subset profile in morbidly obese patients as compared to lean controls, which was not recovered three months after bariatric surgery. The B cell composition of morbidly obese patients after bariatric surgery adjusted towards the profile of lean controls. However, the IL-2 and IFN-γ producing capacity of CD8+ T cells and the IL-2, IFN-γ, TNF-α and IL-10 producing capacity of B cells was not restored three months after bariatric surgery. In conclusion, the data suggest that the immune system has the capacity to recover from the detrimental effects of morbid obesity within three months after bariatric surgery in terms of cell composition; however, this was not seen in terms of cytokine producing capacity. The full restoration of the immune system after bariatric surgery may thus take longer.

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Obesity Accelerates Age Defects in Mouse and Human B Cells

Cited by 17 publications

References 80 publications

COVID-19 mRNA vaccine protects against SARS-CoV-2 Omicron BA.1 infection in diet-induced obese mice through boosting host innate antiviral responses

COVID-19 mRNA vaccine protects against SARS-CoV-2 Omicron BA.1 infection in diet-induced obese mice through boosting host innate antiviral responses

Rituximab-Induced Hypogammaglobulinemia and Risk of Infection in Neuromyelitis Optica Spectrum Disorders

T and B Cell Composition and Cytokine Producing Capacity Before and After Bariatric Surgery

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