Prevalent and persistent new-onset autoantibodies in mild to severe COVID-19

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Oct. 16, 2024

Autoantibodies have been shown to be implied in COVID-19 but the emerging autoantibody repertoire remains largely unexplored. We investigated new-onset 525 healthcare workers and hospitalized patients at five time points over a 16-month period 2020 2021 using proteome-wide targeted protein peptide arrays. Our results show that prevalent autoantibodies against wide range of antigens emerged following SARS-CoV-2 infection relation pre-infectious baseline samples remained elevated for least 12 months. found an increased prevalence after severe demonstrated associations between distinct neuropsychiatric symptoms post-COVID-19. Using epitope mapping, we determined main epitopes selected autoantibodies, validated them independent cohorts neuro-COVID pre-pandemic healthy controls, identified sequence similarities suggestive molecular mimicry conserved fusion Spike glycoprotein. work describes complexity dynamics with supports need continued analysis elucidate mechanisms post-COVID-19 condition.

Language: Английский

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Cellular and molecular determinants mediating the dysregulated germinal center immune dynamics in systemic lupus erythematosus

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 13, 2025

Systemic lupus erythematosus (SLE) is characterized by dysregulated humoral immunity, leading to the generation of autoreactive B cells that can differentiate both within and outside lymph node (LN) follicles. Here, we employed spatial transcriptomics multiplex imaging investigate follicular immune landscaping in situ transcriptomic profile LNs from SLE individuals. Our analysis revealed robust type I IFN plasma cell signatures compared reactive, control Cell deconvolution T subsets are mainly affected fingerprint Dysregulation TFH differentiation was documented i) significant reduction Bcl6hi cells, ii) reduced density potential IL-4 producing associated with impaired signature signaling iii) loss their correlation GC-B cells. This accompanied a marked an enrichment extrafollicular CD19hiCD11chiTbethi, age-associated (ABCs), known for potential. The increased prevalence IL-21hi further reveals hyperactive microenvironment control. Taken together, our findings highlight altered immunological landscape follicles, likely fueled potent inflammatory signals such as sustained and/or IL-21 signaling. work provides novel insights into molecular cellular dynamics, points druggable targets restore tolerance enhance vaccine responses patients.

Language: Английский

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Exploring the correlation between UVB sensitivity and SLE activity: Insights into UVB-driven pathogenesis in lupus erythematosus

Journal of Autoimmunity, Journal Year: 2025, Volume and Issue: 153, P. 103393 - 103393

Published: March 27, 2025

Language: Английский

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Altered baseline immunological state and impaired immune response to SARS-CoV-2 mRNA vaccination in lung transplant recipients

Cell Reports Medicine, Journal Year: 2025, Volume and Issue: unknown, P. 102050 - 102050

Published: April 1, 2025

The effectiveness of COVID-19 mRNA vaccines is diminished in organ transplant patients. Using a multi-omics approach, we investigate the immunological state lung (LTX) recipients at baseline and after SARS-CoV-2 vaccination compared to healthy controls (HCs). LTX patients exhibit immune profile resembling severe sepsis, characterized by elevated pro-inflammatory cytokines (e.g., EN-RAGE [also known as S100A12], interleukin [IL]-6), reduced human leukocyte antigen (HLA)-DR expression on monocytes dendritic cells, impaired cytokine production, increased plasma microbial products. Single-cell RNA sequencing identifies an enriched monocyte cluster marked high S100A family presentation genes. Post vaccination, show antibody, B cell, T cell responses, along with blunted innate signatures. Integrative analysis links these altered features vaccine responses. These findings provide critical insights into immunosuppressed condition their vaccine-induced adaptive

Language: Английский

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Anti-SARS-CoV-2 B and T-Cell Immune Responses Persist 12 Months After mRNA Vaccination with BNT162b2 in Systemic Lupus Erythematosus Patients Independently of Immunosuppressive Therapies

Vaccines, Journal Year: 2025, Volume and Issue: 13(4), P. 396 - 396

Published: April 9, 2025

Background: In response to the SARS-CoV-2 pandemic, a massive vaccination campaign was launched. Nonetheless, concerns arose regarding some peculiar groups of patients, including those affected by Systemic Lupus Erythematosus (SLE), because immune-suppressive drugs routinely administered patients and risk possible disease flares. Since effects third booster in SLE have been poorly assessed, this study aims evaluate immunogenicity safety BNT162b2 vaccine dose, together with immunosuppressive drugs. Methods: A monocentric cohort age- sex-matched healthy controls (HCs) (all vaccinated three homologous doses) were consecutively enrolled 6 months (T1) after their shot. Vaccine evaluated analyzing humoral cellular immune responses at T1 12 (T2). assessing adverse events related (T0) comparing activity among T0, T1, T2. Effects assessed stratifying according therapy vaccination: (1) receiving (IS) or (2) not (Non-IS). Results: At comparable between HC subjects, while significantly higher (p = 0.01). No differences found T2 cohorts. Similarly, both T2, IS Non-IS comparable. Moreover, lupus flares limited mostly mild, no life-threatening reported. Conclusions: The is safe induces an response, which persistent ongoing

Language: Английский

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Bioinformatic analysis and experimental verification reveal expansion of monocyte subsets with an interferon signature in systemic lupus erythematosus patients

Arthritis Research & Therapy, Journal Year: 2025, Volume and Issue: 27(1)

Published: April 25, 2025

Systemic lupus erythematosus (SLE) is a complex autoimmune disorder characterized by chronic inflammation and multi-organ damage. A central factor in SLE pathogenesis the excessive production of type I interferon (IFN-I), which drives immune dysregulation. Monocytes, key components system, significantly contribute to IFN-I production. However, their specific roles remain incompletely understood. This study utilized bioinformatics statistical analyses, including robust rank aggregation (RRA), DESeq2, limma, analyze transcriptome data from peripheral blood mononuclear cells (PBMCs) monocytes patients healthy controls. Single-cell RNA sequencing (scRNA-seq) were processed using Seurat R package identify characterize monocyte subsets with strong IFN-driven gene signature. Flow cytometry was employed validate findings, markers such as CD14, SIGLEC1, IRF7 confirm subset composition. Our research has found that undergo transcriptional reprogramming, upregulation signature genes (ISGs), forming SLE-Related Monocyte Signature (SLERRAsignature). Moreover, composition phagocyte changes, an increase trend proportion CD14Mono8 flare group. The differentially expressed (DEGs) 13 are mainly ISGs, expression ISGs higher severe patients. We identified SIGLEC1+IRF7+ among these for first time discovered this group individuals. In SLE, enrichment score set representing positively correlated severity SLE. Finally, flow confirmed frequency CD14+SIGLEC1+IRF7+ PBMCs compared expansion IFN-I-producing subsets, particularly subset, plays crucial role pathogenesis. may serve potential biomarker therapeutic target managing

Language: Английский

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Chemokines and chemokine receptors: Potential therapeutic targets in systemic lupus erythematosus

Cytokine, Journal Year: 2024, Volume and Issue: 184, P. 156770 - 156770

Published: Sept. 25, 2024

Language: Английский

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Breakthrough SARS-CoV-2 infection in fully vaccinated patients with systemic lupus erythematosus: results from the COVID-19 Vaccination in Autoimmune Disease (COVAD) study

Rheumatology International, Journal Year: 2024, Volume and Issue: 44(10), P. 1923 - 1933

Published: Aug. 13, 2024

Abstract Objective To determine the occurrence of breakthrough COVID-19 infections (BIs) in patients with systemic lupus erythematosus (SLE) compared other rheumatic autoimmune diseases (rAIDs), non-rheumatic (nrAIDs), and healthy controls (HCs). Methods The study was based on data from 7035 fully vaccinated respondents to online COVAD questionnaire SLE (N = 852), rAIDs 3098), or nrAIDs 414), HCs 2671). BI defined as infection occurring individuals ≥ 2 doses (or 1 dose J&J) 14 days after vaccination not 6 months since last vaccine dose. Data were analysed using linear logistic regression models. Results A total 91/852 (10.7%) reported at least one BI. frequency BIs comparable that among (277/2671; p 0.847) nrAID (39/414; 0.552) but higher than (235/3098; 0.005). No demographic factors treatments associated ( 0.05 for all). Joint pain more frequent (odds ratio [OR]: 3.38; 95% confidence interval [CI]: 1.89–6.04; < 0.001) (OR: 2.44; CI: 1.04–5.75; 0.041). Patient did report a hospitalisation need advanced treatment disease HCs, respectively. Conclusion conferred similar protection against terms severity by individuals.

Language: Английский

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Mechanisms Underlying Gender Influence on the Clinical Course and Immunopathogenesis of Systemic Lupus Erythematosus: An Explorative Review

Cureus, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 13, 2024

Systemic lupus erythematosus (SLE) is an autoimmune disorder with a complex clinical course and diverse presentations. The immunopathogenesis of SLE has long intrigued physicians researchers. Despite its extensive global prevalence, there no specific treatment to prevent treat SLE, in the majority patients, management involves controlling disease remissions symptom reactivations or flares. patients suffer from damage different organs body, complicating management. They are predisposed infectious diseases that could contribute enhanced progression. Devising effective strategies requires comprehensive understanding effects influence on immune system. affects females more frequently than men. However, male often severe females. Gender variations have also been noted manifestations SLE. In light this, additional research needed understand these promote progress gender-specific patient strategies. This review aimed compare gender consequences, immunopathogenesis, associated consequences between female patients. An literature search was conducted collect relevant data. PubMed, MEDLINE, Embase, Google Scholar were searched inception present for articles compared outcomes disorders terms among We explored mechanisms underlying gender-based disease-related consequences. Additionally, we provide key updates regarding

Language: Английский

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