Causal relationship between 731 immune cells and the risk of myeloproliferative neoplasms: A 2-sample bidirectional Mendelian randomization study DOI Creative Commons
Yao Wang,

Yang Fei

Medicine, Journal Year: 2024, Volume and Issue: 103(51), P. e40945 - e40945

Published: Dec. 20, 2024

Myeloproliferative neoplasms (MPN) are chronic hematological disorders marked by the abnormal proliferation of bone marrow cells. The most commonly encountered forms polycythemia vera (PV), primary myelofibrosis (PMF), and essential thrombocythemia (ET). These generally associated with increases in blood components, which can lead to conditions like splenomegaly, thrombosis, bleeding tendencies, a heightened risk progressing acute leukemia. Previous research has indicated possible link between immune cells MPN, yet this association is still poorly understood. This study seeks elucidate causal relationship cell characteristics development MPN. In study, we employed Mendelian randomization (MR) investigate potential links 731 traits developing leveraging data from genome-wide studies (GWAS). To ensure robustness our findings, conducted extensive sensitivity analyses assess heterogeneity detect any pleiotropic effects. Moreover, implemented false discovery rate (FDR) correction mitigate positives that may result multiple hypothesis testing, thereby adjusting for statistical biases due comparisons. phenotype IgD on + CD24 - B demonstrated statistically significant protective effect against MPN (PFDR = 0.047). Upon significance threshold PFDR < 0.20, 16 phenotypes were significantly Among these, 11 found exert 5 an elevated highlights various advancing understanding intricate interplay progression

Language: Английский

The interaction of innate immune and adaptive immune system DOI Creative Commons

Ruyuan Wang,

Caini Lan, Kamel Benlagha

et al.

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

Published: Sept. 15, 2024

The innate immune system serves as the body's first line of defense, utilizing pattern recognition receptors like Toll-like to detect pathogens and initiate rapid response mechanisms. Following this initial response, adaptive immunity provides highly specific sustained killing via B cells, T antibodies. Traditionally, it has been assumed that activates immunity; however, recent studies have revealed more complex interactions. This review a detailed dissection composition function systems, emphasizing their synergistic roles in physiological pathological contexts, providing new insights into link between these two forms immunity. Precise regulation both systems at same time is beneficial fight against immune-related diseases, for example, cGAS-STING pathway found play an important role infections cancers. In addition, paper summarizes challenges future directions field immunity, including latest single-cell sequencing technologies, CAR-T cell therapy, checkpoint inhibitors. By summarizing developments, aims enhance our understanding complexity interactions perspectives system.

Language: Английский

Citations

18

Profiling the broad antibody diversity of lymphatic filariasis immune antibody repertoire by deep sequencing DOI
Chia Chiu Lim, Theam Soon Lim

International Journal of Biological Macromolecules, Journal Year: 2025, Volume and Issue: unknown, P. 140037 - 140037

Published: Jan. 1, 2025

Language: Английский

Citations

0

The Importance of Monitoring Antigen-Specific Memory B Cells, and How ImmunoSpot Assays Are Suitable for This Task DOI Creative Commons
Greg A. Kirchenbaum, Graham Pawelec,

Paul Lehmann

et al.

Cells, Journal Year: 2025, Volume and Issue: 14(3), P. 223 - 223

Published: Feb. 5, 2025

Determining an individual’s humoral immune reactivity to a pathogen, autoantigen, or environmental agent is traditionally accomplished through the assessment of specific antibody levels in blood. However, many instances, titers antibodies decline over time and thus do not faithfully reveal prior antigen exposure establishment immunological memory. To estimate competence, it therefore necessary assess functional B cell Here, we describe novel ELISPOT FluoroSpot assays (collectively referred as ImmunoSpot) that can be rapidly developed validated characterize memory (Bmem) repertoire for any desired ex vivo at single-cell resolution. Moreover, multiplexed variants assay enable high-throughput testing antigen-specific cells secreting distinct classes and/or IgG subclasses, with minimal material requirements. ImmunoSpot also measurement affinity distributions within Bmem compartment permit cross-reactivity measurements provide insights into established against future pathogen variants. Collectively, ImmunoSpot® system presented here highly reproducible, readily regulated tests. The newly gained ability monitor should catalyze more comprehensive understanding immunity health disease.

Language: Английский

Citations

0

Low levels of post-vaccination hemagglutination inhibition antibodies and their correlation with influenza protection among healthcare workers during the 2024/2025 A/H1N1 outbreak in Japan DOI Creative Commons
Shohei Yamamoto, Tetsuya Mizoue, Mugen Ujiie

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 7, 2025

Background After the prolonged COVID–19 pandemic, during which seasonal influenza epidemic was suppressed, Japan experienced a record–breaking A/H1N1 outbreak in 2024/2025 season. This situation also raises concern about immunogenicity of annual quadrivalent inactivated vaccine (QIIV). study evaluated post-vaccination hemagglutination inhibition (HI) antibody titers and their association with infection risk among healthcare workers. Methods A serosurvey conducted staff at national medical research center Tokyo December 2024, one month after received QIIV. HI against strains were measured, participants followed for until January 2025. Seroprotection defined as an titer ≥40. Cox proportional hazards model assessed between vaccinated participants. Results Among 1,507 participants, only 12.7% had seroprotective A/H1N1. Around 90% no history least four seasons repeated vaccinations over two seasons. Participants <40 4–fold higher than those dose–response observed, even within range below 40. Relative to <10, 10 20 conferred 47.3% 57.9% protection, respectively. Conclusions period without major epidemic, extremely low Nonetheless, post–vaccination titers, relatively levels, associated supporting benefit vaccines.

Language: Английский

Citations

0

Durability of Functional SARS‐CoV‐2‐Specific Immunological Memory and T Cell Response up to 8–9 Months Postrecovery From COVID‐19 DOI Creative Commons
Diptee Trimbake, Dharmendra Pratap Singh,

Y. K.

et al.

Journal of Immunology Research, Journal Year: 2025, Volume and Issue: 2025(1)

Published: Jan. 1, 2025

Research on long‐term follow‐up in individuals who have recovered from coronavirus disease‐19 (COVID‐19) would yield insights regarding their immunity status and identify those need booster vaccinations. This study evaluated the longevity of severe acute respiratory syndrome 2 (SARS‐CoV‐2)‐specific cellular humoral memory responses, as well T cell effector functionalities, at 1–2 months ( n = 40), 8–9 12 months/1 year 27) following recovery SARS‐CoV‐2 infection. CTL response by enzyme‐linked immunospot (ELISPOT); levels cytokine Bio‐Plex, natural killer (NK), CD4+ helper, CD8+ cytotoxic functionalities using flow cytometry; anti‐SARS‐CoV‐2 IgG ELISA; neutralizing antibodies (NAbs) surrogate virus NAb assay were assessed. The SARS‐CoV‐2‐specific 8−9 postrecovery hand appeared declining. B, B plasma cells, cells sustained up to months. Increased expression CD107a/IFN‐γ NK could be indicative functions. Recovered with positive negative antibody displayed 1 months, respectively, emphasizing durabilty regardless status. Overall, exhibited robust immunological memory, functionality against that persists for least

Language: Английский

Citations

0

Functional insights of an uncommon hypomorphic variant in IL2RG as a monogenic cause of CVID-like disease with antibody deficiency and T CD4 lymphopenia DOI Creative Commons
Andrea González‐Torbay,

Keren Reche-Yebra,

Álvaro Clemente-Bernal

et al.

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

Published: March 18, 2025

Over the last decade, identification of hypomorphic variants in patients previously diagnosed with Common Variable Immunodeficiency (CVID) has led to association milder phenotypes IL2RG gene that are usually related severe combined immunodeficiency. Indeed, several revertant mosaicisms have been described cases gene. Our main objective herein was functional characterization p. (Pro58Thr) variant an adult patient antibody deficiency and moderate CD4+ T cell lymphopenia. Evaluation included a clinical examination complete analysis peripheral blood phenotype. To further explore functionality we selected downstream signaling readouts, namely STAT3 STAT5 phosphorylation, NK degranulation B- T-cell proliferation capacity vitro, which can be measured by flow cytometry, reflect strength homeostatic pathways resting cells after activation. The presented reduced CD132 expression conserved T- B-cell vitro. However, found intracellular IL2γc is affected, phosphorylation IL-21 stimulation B CD4 cells. In addition, showed response IL-2, not so evident CD8+ impaired upon PHA IL-2 as well plasmablast differentiation We conclude functionally variant, reported previously. Although less than rest lymphocyte subsets, did detect reversion isolated CD8+, CD4+, CD19+ or

Language: Английский

Citations

0

Autophagy in tumor immune escape and immunotherapy DOI Creative Commons
Huan Wang, Peng Sun,

Xijing Yuan

et al.

Molecular Cancer, Journal Year: 2025, Volume and Issue: 24(1)

Published: March 19, 2025

The immunotherapy targeting tumor immune escape mechanisms has become a critical strategy in anticancer treatment; however, the challenge of resistance remains significant. Autophagy, cellular response to various stressors, involves degradation damaged proteins and organelles via lysosomal pathways, maintaining homeostasis. This process not only supports cell survival but also profoundly impacts efficacy cancer immunotherapies. modulation autophagy cells or exerts dual effects on immunotherapy. However, mechanistic details how influences system therapy remain inadequately understood. Given this complexity, deeper understanding role tumor-immune landscape could reveal novel therapeutic avenues. By manipulating appropriately, it may be possible overcome enhance effectiveness immunotherapeutic strategies. article summarizes immunity, its relationship with immunotherapy, potential benefits strengthen antitumor responses optimize outcomes

Language: Английский

Citations

0

Within-Host Mathematical Models to Study Antibody Kinetics after the Prophylactic Ebola Vaccine in the Democratic Republic of the Congo DOI
Irene Garcia-Fogeda, Steven Abrams, Stijn Vanhee

et al.

Published: Jan. 1, 2025

Language: Английский

Citations

0

Dendritic cell expression of MyD88 is required for rotavirus-induced B cell activation DOI Creative Commons
Sarah E. Blutt,

Amber Miller,

Margaret E. Conner

et al.

Journal of Virology, Journal Year: 2025, Volume and Issue: unknown

Published: April 30, 2025

ABSTRACT Intestinal IgA, produced by local intestinal B cells, is thought to play a major role in protection against infections. Rotavirus, well-characterized virus, induces rapid viral-specific IgA response that occurs the absence of T cells. Previous work has indicated dendritic cells facilitate early rotavirus. To determine whether Peyer's patch cell activation associated with rotavirus infection mice requires we depleted and assessed activation. Depletion CD11c + vivo prior resulted complete abrogation With use vitro cell-based assays, , but not or CD11b was shown be essential for rotavirus-induced Investigation several pathways revealed expression MyD88 signaling through type I interferon receptor were critical ability virus induce These findings indicate can modulate responses viruses toll-like pathways. IMPORTANCE Dendritic are key mediators immune intestine. They capture process antigens present these which produce antibody clearance from reinfection. In presented here, demonstrate MyD88, component pattern recognition pathways, classical pathway molecules such as BAFF APRIL, Our emphasize important initiating regulating including cell-independent A consideration production an feature development therapeutic preventive modalities combat viral

Language: Английский

Citations

0

Measuring Human Memory B Cells in Autoimmunity Using Enzyme-Linked ImmunoSpot DOI Creative Commons

Georgia Stylianou,

Greg A. Kirchenbaum,

Paul Lehmann

et al.

Biomolecules, Journal Year: 2025, Volume and Issue: 15(5), P. 643 - 643

Published: April 30, 2025

The measurement of serum antibodies that specifically recognize self-antigens is a critical diagnostic in autoimmunity. A limitation such an approach sensitivity to detect the antibody, particularly when abundant body may bind and sequester circulating specific antibodies. presence memory B cells (Bmem) provide more sensitive robust indicator autoimmune response, as suggested for certain anti-viral responses. cell enzyme-linked ImmunoSpot (ELISPOT) capable detecting antigen-specific Bmem blood at single level, following stimulation peripheral mononuclear (PBMCs) expand differentiate into functional antibody-secreting (ASCs). While this assay has been widely utilized infectious diseases vaccination, detection difficult autoantigens due self-tolerance tissue compartmentalization immune responses, making autoantigen-specific rare circulation. cycles re-activation become ASCs, reflect disease flare-ups autoimmunity, are not well defined. For several (ADs), targeting via depleting monoclonal proven be effective treatment, where likely being targeted. autoantigen-reactive aid diagnosis staging clinical severity, or metric efficacious treatments, thus providing additional informative biomarker ADs. How ELISPOT characterize human ADs described here, including advantages disadvantages assay.

Language: Английский

Citations

0