Dysregulated naive B cells and de novo autoreactivity in severe COVID-19

Nature, Год журнала: 2022, Номер 611(7934), С. 139 - 147

Опубликована: Авг. 31, 2022

Abstract Severe SARS-CoV-2 infection 1 has been associated with highly inflammatory immune activation since the earliest days of COVID-19 pandemic 2–5 . More recently, these responses have emergence self-reactive antibodies pathologic potential 6–10 , although their origins and resolution remained unclear 11 Previously, we others identified extrafollicular B cell activation, a pathway formation new autoreactive in chronic autoimmunity 12,13 as dominant feature severe critical (refs. 14–18 ). Here, using single-cell repertoire analysis patients mild disease, identify expansion naive-derived, low-mutation IgG1 population antibody-secreting cells (ASCs) reflecting features low selective pressure. These correlate progressive, broad, clinically relevant autoreactivity, particularly directed against nuclear antigens carbamylated proteins, emerging 10–15 after onset symptoms. Detailed low-selection compartment shows high frequency clonotypes specific for both autoantigens, including pathogenic autoantibodies glomerular basement membrane. We further contraction this on recovery, re-establishment tolerance standards concomitant loss acute-derived ASCs irrespective antigen specificity. However, serological autoreactivity persists subset postacute sequelae, raising important questions to contribution continuing symptomology recovery. In summary, study demonstrates origins, breadth COVID-19, implications early intervention treatment post-COVID sequelae.

Язык: Английский

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Comparison of Seroconversion in Children and Adults With Mild COVID-19

JAMA Network Open, Год журнала: 2022, Номер 5(3), С. e221313 - e221313

Опубликована: Март 9, 2022

Importance

The immune response in children with SARS-CoV-2 infection is not well understood.

Objective

To compare seroconversion nonhospitalized and adults mild identify factors that are associated seroconversion.

Design, Setting, Participants

This household cohort study of collected weekly nasopharyngeal throat swabs blood samples during the acute (median, 7 days for 12 [IQR, 4-13] days) convalescent 41 31-49] periods after polymerase chain reaction (PCR) diagnosis analysis. Participants were recruited at Royal Children's Hospital, Melbourne, Australia, from May 10 to October 28, 2020. included patients who had a SARS-CoV-2–positive or oropharyngeal swab specimen using PCR

Main Outcomes Measures

immunoglobulin G (IgG) cellular (T cell B cell) responses adults. Seroconversion was defined by seropositivity all 3 (an in-house enzyme-linked immunosorbent assay [ELISA] 2 commercial assays: S1/S2 IgG antibody ELISA) serological assays.

Results

Among 108 participants findings, 57 (35 boys [61.4%]; median age, 4 2-10] years) 51 (28 women [54.9%]; 37 34-45] years). Using established assays, lower proportion compared (20 54 [37.0%] vs 32 42 [76.2%];P < .001). result viral load, which similar (mean [SD] cycle threshold [Ct] value, 28.58 [6.83] 24.14 [8.47];P = .09). In addition, age sex within (median 2-14] years both seropositive seronegative groups; sex, 21 girls [47.6%] 33 [30.3%]) ages, 40 34-39 years]; 18 24 [75.0%] 14 men [77.8%]) (P> .05 comparisons between groups). Symptomatic 3-fold higher levels than asymptomatic 227.5 133.7-521.6] 75.3 36.9-113.6] IU/mL), whereas no differences observed regardless symptoms. Moreover,

Conclusions Relevance

findings this suggest among COVID-19, may be less likely have despite loads. finding has implications future protection interpretation serosurveys involve children. Further research understand why development symptoms potentially vaccine clinical scientific importance.

Язык: Английский

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Remodeling of T Cell Dynamics During Long COVID Is Dependent on Severity of SARS-CoV-2 Infection

Frontiers in Immunology, Год журнала: 2022, Номер 13

Опубликована: Июнь 10, 2022

Several COVID-19 convalescents suffer from the post-acute COVID-syndrome (PACS)/long COVID, with symptoms that include fatigue, dyspnea, pulmonary fibrosis, cognitive dysfunctions or even stroke. Given scale of worldwide infections, long-term recovery and integrative health-care in nearest future, it is critical to understand cellular molecular mechanisms as well possible predictors longitudinal post-COVID-19 responses convalescent individuals. The immune system T cell alterations are proposed drivers COVID syndrome. However, despite number studies on COVID-19, many them addressed only severe short-term responses. Here, we performed mild, moderate COVID-19-convalescent patients, at two time points (3 6 months infection), assess dynamics cells landscape, integrated patients-reported symptoms. We show among subsets exhibit different, severity- time-dependent dynamics, result a polarization towards an exhausted/senescent state CD4+ CD8+ perturbances Tregs. In particular, high proportion CD57+ terminal effector cells, together significant decrease naïve population, augmented granzyme B IFN-γ production unresolved inflammation after infection. Mild showed increased naïve, decreased central memory Treg subsets. Patients all severity groups can be predisposed long symptoms, fatigue not necessarily related dysfunctions, was found convalescents. conclusion, functional remodeling could seen two-step process, leading distinct states Our data imply attenuation blocking might influence post-COVID either search for any treatment prevent PACS further complications mandatory patients SARS-CoV-2 infection, those suffering COVID-19.

Язык: Английский

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IgD−CD27− double negative (DN) B cells: Origins and functions in health and disease

Immunology Letters, Год журнала: 2023, Номер 255, С. 67 - 76

Опубликована: Март 1, 2023

Язык: Английский

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SARS-CoV-2 immunity in animal models

Cellular and Molecular Immunology, Год журнала: 2024, Номер 21(2), С. 119 - 133

Опубликована: Янв. 18, 2024

The COVID-19 pandemic, which was caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a worldwide health crisis due to its transmissibility. SARS-CoV-2 infection results in illness and can lead significant complications affected individuals. These encompass symptoms such as coughing, distress, fever, infectious shock, distress (ARDS), even multiple-organ failure. Animal models serve crucial tools for investigating pathogenic mechanisms, immune responses, escape antiviral drug development, vaccines against SARS-CoV-2. Currently, various animal infection, nonhuman primates (NHPs), ferrets, hamsters, many different mouse models, have been developed. Each model possesses distinctive features applications. In this review, we elucidate the response elicited patients provide an overview of characteristics mainly used well corresponding responses applications these models. A comparative analysis transcriptomic alterations lungs from revealed that K18-hACE2 mouse-adapted virus exhibited highest similarity with deceased patients. Finally, highlighted current gaps related research between studies clinical investigations, underscoring lingering scientific questions demand further clarification.

Язык: Английский

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SARS-CoV-2 Vaccine Induced Atypical Immune Responses in Antibody Defects: Everybody Does their Best

Journal of Clinical Immunology, Год журнала: 2021, Номер 41(8), С. 1709 - 1722

Опубликована: Окт. 20, 2021

Abstract Background Data on immune responses to SARS-CoV-2 in patients with Primary Antibody Deficiencies (PAD) are limited infected and heterogeneous cohorts after immunization. Methods Forty-one Common Variable Immune (CVID), six X-linked Agammaglobulinemia (XLA), 28 healthy age-matched controls (HD) were analyzed for anti-Spike anti-receptor binding domain (RBD) antibody production, generation of Spike-specific memory B-cells, T-cells before vaccination one week the second dose BNT162b2 vaccine. Results The vaccine induced IgG IgA all HD 20% naive CVID patients. Anti-Spike detectable 4 out 7 previously boosted seven by subsequent immunization raising higher levels than naïve infection. While generated RBD-specific atypical while B-cells undetectable patients, indicating incapability generate this new specificity. Specific T-cell evident defective 30% CVID. All but patient XLA responded specific only. Conclusion In PAD early occurred, possibly extra-follicular or incomplete germinal center reactions. If these might result a partial protection from infection reinfection is now unknown. Our data suggests that more effectively primes response alone, suggesting need third not infected.

Язык: Английский

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The Dynamics of B Cell Aging in Health and Disease

Frontiers in Immunology, Год журнала: 2021, Номер 12

Опубликована: Окт. 5, 2021

Aging is considered to be an important risk factor for several inflammatory diseases. B cells play a major role in chronic diseases by antibody secretion, antigen presentation and T cell regulation. Different subsets have been implicated infections multiple autoimmune Since aging decreases numbers, affects impairs responses, the aged expected impacts on development progression of these In this review, we summarize health disease settings, such as atherosclerotic disease. Furthermore, provide overview age-related changes function with respect their impact

Язык: Английский

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Immune responses in mildly versus critically ill COVID-19 patients

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Янв. 30, 2023

The current coronavirus pandemic (COVID-19), caused by SARS-CoV-2, has had devastating effects on the global health and economic system. cellular molecular mediators of both innate adaptive immune systems are critical in controlling SARS-CoV-2 infections. However, dysregulated inflammatory responses imbalanced immunity may contribute to tissue destruction pathogenesis disease. Important mechanisms severe forms COVID-19 include overproduction cytokines, impairment type I IFN response, overactivation neutrophils macrophages, decreased frequencies DC cells, NK cells ILCs, complement activation, lymphopenia, Th1 Treg hypoactivation, Th2 Th17 hyperactivation, as well clonal diversity B lymphocyte function. Given relationship between disease severity an system, scientists have been led manipulate system a therapeutic approach. For example, anti-cytokine, cell, IVIG therapies received attention treatment COVID-19. In this review, role development progression is discussed, focusing aspects mild vs. Moreover, some immune- based approaches being investigated. Understanding key processes involved developing agents optimizing related strategies.

Язык: Английский

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Innate and Adaptive Immunity during SARS-CoV-2 Infection: Biomolecular Cellular Markers and Mechanisms

Vaccines, Год журнала: 2023, Номер 11(2), С. 408 - 408

Опубликована: Фев. 10, 2023

The coronavirus 2019 (COVID-19) pandemic was caused by a positive sense single-stranded RNA (ssRNA) severe acute respiratory syndrome 2 (SARS-CoV-2). However, other human coronaviruses (hCoVs) exist. Historical pandemics include smallpox and influenza, with efficacious therapeutics utilized to reduce overall disease burden through effectively targeting competent host immune system response. is composed of primary/secondary lymphoid structures initially eight types cell types, many subtypes, traversing membranes utilizing signaling cascades that contribute towards clearance pathogenic proteins. Other proteins discussed cluster differentiation (CD) markers, major histocompatibility complexes (MHC), pleiotropic interleukins (IL), chemokines (CXC). historical concepts immunity are the innate adaptive systems. represented T cells, B antibodies. macrophages, neutrophils, dendritic complement system. viruses can affect regulate cycle progression for example, in cancers papillomavirus (HPV: cervical carcinoma), Epstein-Barr virus (EBV: lymphoma), Hepatitis C (HB/HC: hepatocellular carcinoma) Leukemia Virus-1 (T leukemia). Bacterial infections also increase risk developing cancer (e.g.,

Язык: Английский

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Functions of double‐negative B cells in autoimmune diseases, infections, and cancers

EMBO Molecular Medicine, Год журнала: 2023, Номер 15(9)

Опубликована: Июнь 5, 2023

Abstract Most mature B cells can be divided into four subtypes based on the expression of surface markers IgD and CD27: + CD27 − naïve cells, unswitched memory switched double‐negative (DN) cells. Despite their small population size in normal peripheral blood, DN play integral roles various diseases. For example, they generate autoimmunity autoimmune conditions, while these may both antipathogenic responses COVID‐19, or act a purely capacity malaria. Recently, have been identified nasopharyngeal carcinoma non‐small‐cell lung cancers, where an immunosuppressive role. The distinct functions that different diseases suggest are heterogeneous B‐cell population. Therefore, further study mechanisms underlying involvement is essential for understanding pathogenesis development therapeutic strategies. Further research thus warranted to characterize detail.

Язык: Английский

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