Phenotypic and Functional Characterization of Double Negative B Cells in the Blood of Individuals With Obesity

Frasca, Daniela; Diaz, Alain; Romero, Maria; Blomberg, Bonnie B.

doi:10.3389/fimmu.2021.616650

Cited by 41 publications

(47 citation statements)

References 62 publications

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“…Control ELISA plates were coated with BSA at a concentration of 10 µg/mL. MDA-specific optical density (OD) values were calculated by subtracting BSA OD values from MDA-BSA OD values [ 21 , 24 ].…”

Section: Materials/subjects and Methodsmentioning

confidence: 99%

“…Protein content was determined by Bradford [ 25 ]. AD at a concentration of 10 µg/mL were used to coat ELISA plates [ 21 , 24 ].…”

Section: Materials/subjects and Methodsmentioning

confidence: 99%

“…We measured the presence of neutralizing antibodies and autoimmune antibodies specific for malondialdehyde (MDA), which is used as a marker of oxidative stress and lipid peroxidation, and for adipocyte-derived protein antigens (AD), established markers of cell death in the obese adipose tissue (AT). This study included uninfected controls since obesity per se is associated with the secretion of autoimmune antibodies, as previously demonstrated [ 21 – 23 ]. We hypothesized that SARS-CoV-2 infection in COVID-19 patients with obesity induces oxidative stress and tissue damage, leading to cell death and release of intracellular antigens that are not known to be immunogenic autoantigens, and more in obese than in lean patients.…”

Section: Introductionmentioning

confidence: 99%

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The majority of SARS-CoV-2-specific antibodies in COVID-19 patients with obesity are autoimmune and not neutralizing

et al. 2021

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Background/objectives Obesity decreases the secretion of SARS-CoV-2-specific IgG antibodies in the blood of COVID-19 patients. How obesity impacts the quality of the antibodies secreted, however, is not understood. Therefore, the objective of this study is to evaluate the presence of neutralizing versus autoimmune antibodies in COVID-19 patients with obesity. Subjects/methods Thirty serum samples from individuals who tested positive for SARS-CoV-2 infection by RT-PCR were collected from inpatient and outpatient settings. Of these, 15 were lean (BMI < 25) and 15 were obese (BMI ≥ 30). Control serum samples were from 30 uninfected individuals, age-, gender-, and BMI-matched, recruited before the current pandemic. Neutralizing and autoimmune antibodies were measured by ELISA. IgG autoimmune antibodies were specific for malondialdehyde (MDA), a marker of oxidative stress and lipid peroxidation, and for adipocyte-derived protein antigens (AD), markers of virus-induced cell death in the obese adipose tissue. Results SARS-CoV-2 infection induces neutralizing antibodies in all lean but only in few obese COVID-19 patients. SARS-CoV-2 infection also induces anti-MDA and anti-AD autoimmune antibodies more in lean than in obese patients as compared to uninfected controls. Serum levels of these autoimmune antibodies, however, are always higher in obese versus lean COVID-19 patients. Moreover, because the autoimmune antibodies found in serum samples of COVID-19 patients have been correlated with serum levels of C-reactive protein (CRP), a general marker of inflammation, we also evaluated the association of anti-MDA and anti-AD antibodies with serum CRP and found a positive association between CRP and autoimmune antibodies. Conclusions Our results highlight the importance of evaluating the quality of the antibody response in COVID-19 patients with obesity, particularly the presence of autoimmune antibodies, and identify biomarkers of self-tolerance breakdown. This is crucial to protect this vulnerable population at higher risk of responding poorly to infection with SARS-CoV-2 than lean controls.

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Section: Materials/subjects and Methodsmentioning

confidence: 99%

“…Protein content was determined by Bradford [ 25 ]. AD at a concentration of 10 µg/mL were used to coat ELISA plates [ 21 , 24 ].…”

Section: Materials/subjects and Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The majority of SARS-CoV-2-specific antibodies in COVID-19 patients with obesity are autoimmune and not neutralizing

et al. 2021

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“… 16 , 18 , 20 , 21 Truth is that all these terms referred to B cell populations that share a number of features and are enriched in the peripheral blood of both elderly healthy individuals and people with chronic infectious diseases or inflammatory conditions, such as autoimmune disorders, obesity and cancer. 16 – 20 , 24 – 26 A recent study however, based on transcriptomic and IgH repertoire analyses of B cells, questions the equivalence of all these populations. 27 Here, we shall discuss the DN B cell population and its subsets, as well as the DN relationship to other B cells arising in autoimmunity and infections.…”

Section: The Population Of Double-negative (Dn) B Cellsmentioning

confidence: 99%

Double Negative (DN) B cells: A connecting bridge between rheumatic diseases and COVID-19?

Sachinidis

Garyfallos

2021

MJR

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Double Negative (DN) B cells constitute a B cell population that lacks expression of immunoglobulin D and CD27 memory marker. These cells expand in elderly healthy individuals, but also accumulate prematurely in autoimmune and infectious diseases. COVID-19 is a pandemic infectious disease caused by SARS-CoV-2, a coronavirus that was first observed in Wuhan, China in December 2019. In its more severe cases, COVID-19 causes severe pneumonia and acute respiratory syndrome with high morbidity and mortality. Recent studies have revealed that the extrafollicular DN2 B cell subset, previously described in lupus patients, does also expand in severe and/or critical groups of COVID-19 patients. These DN2 cells correlate with disease severity and laboratory parameters of inflammation. However, their exact role and function in COVID-19 require to be further investigated. In this review, we highlight the DN immune responses in both rheumatic diseases and COVID-19, and we point out the importance of clarifying DN’s role in the immunopathology of the aforementioned infection, as it could probably enable better management of rheumatic diseases during the pandemic. Of note, the symptomatology of COVID-19, as well as the potential outcome of death, have given rise to a worldwide concern and scare of exposition to SARS-CoV-2, especially among the rheumatological patients who believe to be at higher risk due to their immunological background and the immunosuppressive therapies. Nevertheless, there is no convincing evidence so far that these patients are truly at higher risk than others.

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“…In this study, we have measured the presence of antibodies with autoimmune specificities in the sera of lean (BMI <25) and obese (BMI>30) COVID-19 patients, as compared to age-, gender- and BMI-matched uninfected controls, without previous history of autoimmunity. This study included uninfected controls since obesity per se is associated with the secretion of autoimmune antibodies, as previously demonstrated (28, 34, 35). It has been recently shown that the sera of adult COVID-19 patients contain antibodies with autoimmune specificities (36).…”

Section: Introductionmentioning

confidence: 99%

SARS-CoV-2 infection induces autoimmune antibody secretion more in lean than in obese COVID-19 patients

Frasca

Reidy

Romero

et al. 2021

Preprint

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Background/Objectives: Obesity decreases the secretion of SARS-CoV-2-specific IgG antibodies in the blood of COVID-19 patients. How obesity impacts the secretion of autoimmune antibodies in COVID-19 patients, however, is not understood. The serum of adult COVID-19 patients contains autoimmune antibodies generated in response to virus-induced tissue damage and cell death leading to the release of intracellular antigens not known to be immunogenic autoantigens. The objective of this study is to evaluate the presence of autoimmune antibodies in COVID-19 patients with obesity. Subjects/Methods: Thirty serum samples from individuals who tested positive for SARS-CoV-2 infection by RT-PCR were collected from inpatient and outpatient settings. Of these, 15 were lean (BMI<25), and 15 were obese (BMI ≥30). Control serum samples were from 30 uninfected individuals, age- gender- and BMI-matched, recruited before the current pandemic. Serum IgG antibodies against two autoimmune specificities, as well as against SARS-CoV-2 Spike protein, were measured by ELISA. IgG autoimmune antibodies were specific for malondialdehyde (MDA), a marker of oxidative stress and lipid peroxidation, and for adipocyte-derived protein antigens (AD), markers of virus-induced cell death in the obese AT. Results: Our results show that SARS-CoV-2 infection induces anti-MDA and anti-AD autoimmune antibodies more in lean than in obese patients as compared to uninfected controls. Serum levels of these autoimmune antibodies, however, are always higher in obese versus lean COVID-19 patients. Moreover, because the autoimmune antibodies found in serum samples of COVID-19 patients have been correlated with serum levels of C-reactive protein (CRP), a general marker of inflammation, we also evaluated the association of anti-MDA and anti-AT antibodies with serum CRP and found a significant association between CRP and autoimmune antibodies in our cohort of lean and obese COVID-19 patients. Conclusions: Our results highlight the importance of evaluating the quality of the antibody response in COVID-19 patients with obesity, particularly the presence of autoimmune antibodies, and identify biomarkers of self-tolerance breakdown. This is crucial to protect this vulnerable population that is at higher risk of responding poorly to infection with SARS-CoV-2 compared to lean controls.

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Phenotypic and Functional Characterization of Double Negative B Cells in the Blood of Individuals With Obesity

Cited by 41 publications

References 62 publications

The majority of SARS-CoV-2-specific antibodies in COVID-19 patients with obesity are autoimmune and not neutralizing

The majority of SARS-CoV-2-specific antibodies in COVID-19 patients with obesity are autoimmune and not neutralizing

Double Negative (DN) B cells: A connecting bridge between rheumatic diseases and COVID-19?

SARS-CoV-2 infection induces autoimmune antibody secretion more in lean than in obese COVID-19 patients

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