An unexpected IgE anti-receptor binding domain response following natural infection and different types of SARS-CoV-2 vaccines

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Aug. 28, 2024

Humoral response to SARS-CoV-2 has been studied, predominantly the classical IgG and its subclasses. Although IgE antibodies are typically specific allergens or parasites, a few reports describe their production in other viruses. Here, we investigated receptor binding domain (RBD) of Brazilian cohort following natural infection vaccination. Samples from 59 volunteers were assessed after (COVID-19), primary immunization with vectored (ChAdOx1) inactivated (CoronaVac) vaccines, booster mRNA (BNT162b2) vaccine. Natural COVID-19 induced IgE, but vaccination increased levels. Subjects vaccinated two doses ChAdOx1 exhibited more robust than those immunized CoronaVac; however, boosting BNT162b2, all groups presented similar showed intermediate-to-high avidity, especially We also found IgG4 antibodies, mainly booster, they moderately correlated IgE. ELISA results confirmed by control assays, using depletion protein G lack reactivity heterologous antigen. In our cohort, no clinical data could be associated response. advocate for further research on role viral immunity, extending beyond allergies parasitic infections.

Language: Английский

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Complement activity and autophagy are dysregulated in the lungs of patients with nonresolvable COVID-19 requiring lung transplantation

Respiratory Research, Journal Year: 2025, Volume and Issue: 26(1)

Published: Feb. 27, 2025

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced disease 2019 (COVID-19) pandemic has challenged the current understanding of complement cascade mechanisms host immune responses during infection-induced nonresolvable lung disease. While system is involved in opsonization and phagocytosis invading pathogens, uncontrolled activation also leads to aberrant autophagic response tissue damage. Our recent study revealed unique pathologic fibrotic signature genes associated with epithelial bronchiolization tissues patients COVID-19 (NR-COVID-19) requiring transplantation. However, there a knowledge gap if components are modulated contribute damage phenotype NR-COVID-19. We, therefore, aimed role factors their corresponding regulatory proteins pathogenesis We further examined association mediators response. observed significant upregulation expression classical pathway factor C1qrs alternative C3 C5a, as well anaphylatoxin receptor C5aR1, NR-COVID-19 tissues. Of note, protein, decay accelerating (DAF; CD55) was significantly downregulated at both transcript protein levels lungs, indicating dampened protective Furthermore, we decreased autophagy PPARγ LC3a/b, which corroborated by P C3b CR1, impaired clearance damaged cells that may patients. Thus, our previously unrecognized dysregulation cell death cells, promote patients, ultimately necessitating identified network dysregulated activity indicates interplay receptor-mediated modulation potential therapeutic targets for treating

Language: Английский

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Understanding IgM Structure and Biology to Engineer New Antibody Therapeutics

BioDrugs, Journal Year: 2025, Volume and Issue: unknown

Published: April 16, 2025

Immunoglobulin M (IgM) antibodies are an essential and conserved part of adaptive immunity. IgMs assemble into pentamers hexamers that bind to antigens with high avidity. Pentamers incorporate a small protein called J-chain (JC) is important for their transcytosis via the poly-immunoglobulin receptor (pIgR). IgM can efficiently activate complement interact different Fc receptors (FcμR, Fcα/μR, pIgR) trigger distinct effector functions biodistribution. Even if these features have made clinical use attractive over past decades, there currently no approved therapeutic on market. In this review, we summarize recent advances in knowledge biogenesis structure discuss opportunities IgG arising from avidity, target clustering, binding receptors, activation, transcytosis, engineering opportunities. addition, possibilities outstanding challenges production IgM, including available technologies purification. Finally, review preclinical data showing outperforms various vitro assays but still fails pass through trials successfully. Challenges remain development, such as need better understanding biology facilitate smoother transition preclinic successful trials.

Language: Английский

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Clinical glycoproteomics: methods and diseases

MedComm, Journal Year: 2024, Volume and Issue: 5(10)

Published: Oct. 1, 2024

Abstract Glycoproteins, representing a significant proportion of posttranslational products, play pivotal roles in various biological processes, such as signal transduction and immune response. Abnormal glycosylation may lead to structural functional changes glycoprotein, which is closely related the occurrence development diseases. Consequently, exploring protein can shed light on mechanisms behind disease manifestation pave way for innovative diagnostic therapeutic strategies. Nonetheless, study clinical glycoproteomics fraught with challenges due low abundance intricate structures glycosylation. Recent advancements mass spectrometry‐based have improved our ability identify abnormal glycoproteins samples. In this review, we aim provide comprehensive overview foundational principles recent glycoproteomic methodologies applications. Furthermore, discussed typical characteristics, underlying functions, diseases, brain cardiovascular cancers, kidney metabolic Additionally, highlighted potential avenues future glycoproteomics. These insights provided review will enhance comprehension methods diseases promote elucidation pathogenesis discovery novel biomarkers targets.

Language: Английский

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An unexpected IgE anti-Receptor binding domain response following natural infection and different types of SARS-CoV-2 vaccines

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: April 24, 2024

The humoral response of SARS-CoV-2 has been studied, primarily focusing on the classical IgG and subclasses. Although IgE antibodies are typically specific to allergens or parasites, a few reports describe its production in other viruses. Here, we investigated IgE-specific Receptor Binding Domain (RBD) Brazilian cohort following natural infection vaccination. Samples from 59 volunteers were assessed after (COVID-19), primary immunization with vectored (ChAdOx1) inactivated (CoronaVac) vaccines, booster mRNA (BNT162b2) vaccine. Natural COVID-19 induced IgE, but vaccination increased levels. Subjects vaccinated two doses ChAdOx1 exhibited more robust than those CoronaVac; however, boosting BNT162b2, all groups had similar presented intermediate-to-high avidity, especially booster. We also found IgG4 antibodies, mainly booster, levels moderate correlation IgE. ELISA results confirmed by controls assays, using depletion protein G lack reactivity heterologous antigen. In our cohort, no clinical data could be associated response. encourage studies about role immunity, beyond allergies parasitic infections.

Language: Английский

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Impaired mucosal IgA response in patients with severe COVID-19

Emerging Microbes & Infections, Journal Year: 2024, Volume and Issue: 13(1)

Published: Oct. 2, 2024

Several studies have investigated the antibody response to SARS-CoV-2, focusing particularly on systemic humoral immune and production of immunoglobulin G (IgG) antibodies. IgA antibodies play a crucial role in protecting against respiratory viral infections but also been associated with pathophysiology COVID-19. We performed prospective study 169 COVID-19 patients - 50 critical/severe (ICU), 47 moderate (Non-ICU), 72 asymptomatic explore SARS-CoV-2 infection. found that early strongly induced severe disease did not block IgG neutralization functions activated FcRs more effectively than IgG. However, even if SIgA levels were high, mucosal could control infection disease. Our findings highlight complexity exhibiting high strong neutralizing capacity cases, together higher IgA-FcR activation patients. They suggest need for further research fully understand its structural alterations tissues cases impact these progression.

Language: Английский

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The evolution of flexibility and function in the Fc domains of IgM, IgY, and IgE

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Oct. 9, 2024

Introduction Antibody Fc regions harbour the binding sites for receptors that mediate effector functions following antigen engagement by Fab regions. An extended “hinge” region in IgG allows flexibility between and Fc, but both most primitive antibody, IgM, evolutionarily more recent IgE, hinge is replaced an additional domain pair homodimeric six-domain region. This permits within region, which has been exploited nature to modulate antibody functions. Thus, pentameric or hexameric appear adopt a planar conformation solution until causes conformational change exposes complement sites. In contrast, IgE-Fc principally adopts acutely bent solution, of different controlled degree bending, there allosteric communication receptor Methods We sought trace evolution diversity from IgM IgE via intermediate avian IgY studying conformations their small-angle X-ray scattering. compared four extant proteins: human IgM-Fc homodimer, chicken IgY-Fc, platypus IgE-Fc, IgE-Fc. These are examples proteins first appeared jawed fish [425 million years ago (mya)], tetrapod (310 mya), monotreme (166 hominid (2.5 mya) clades, respectively. Results discussion analysed scattering curves terms contributions pool variously models chosen non-negative linear least-squares algorithm found form series proportion material increases: < IgY-Fc plIgE-Fc huIgE-Fc. follows order appearance evolution. For huIgM-Fc although none bent, significant fraction protein sufficiently expose C1q-binding site, it predominantly fully conformation. huIgE-Fc be as expected earlier studies. this structural analysis complete exhibits ensemble extended, reflecting IgY’s position evolutionary IgE.

Language: Английский

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Role of Xenosialylation in Post-Infectious and Post-Vaccination Complications, Including Covid-19 and Anti-SARS-CoV-2 Vaccination

Journal of Inflammation Research, Journal Year: 2024, Volume and Issue: Volume 17, P. 8385 - 8394

Published: Nov. 1, 2024

The host glycosylation mechanism, with sialic acids as a key component, is essential for synthesizing carbohydrate components in viral glycoproteins. We hypothesize correlation between the presence of Neu5Gc on tissue and development infectious complications, adverse vaccine reactions, autoimmune diseases. In certain mammals, including humans, loss Cytidine Monophospho-N-Acetylneuraminic Acid Hydroxylase gene (negative-CMAH) prevents synthesis Neu5Gc, which acts Mammalian-associated Carbohydrate Antigen (MCA), (XeSiAs-Neu5Gc). When negative-CMAH species consume products from positive-CMAH mammals or are exposed to non-human cell-derived medicines, can be integrated into their glycocalyx through process called xenosialylation, eliciting an inflammatory response (xenosialitis) prompting production circulating anti-Neu5Gc antibodies aimed at eliminating Neu5Gc. that case neutralizing antiviral infections vaccinations-including those SARS-CoV-2-may cross-react XeSiAs-Neu5Gc glycans, these resemble envelope antigens produced by host's glycosylation. Additionally, may also react other antibodies, newly formed ones XeSiAs-Neu5Gc-contaminated Fc region. This lead serum removal anti-inflammatory leaving only hyperinflammatory IgG agalactosylated antibodies. Such conditions seen various combination antibody cross-reaction region intensify severe responses like cytokine storms coagulopathies COVID-19 patients vaccinated. Assessing levels total could valuable method identifying risk complications vaccinations, SARS-CoV-2. strategy deepen our understanding pathogenesis diseases linked post-infectious post-vaccination particularly viruses utilizing machinery, such SARS-CoV-2, IAV, EBV, others.

Language: Английский

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