-
Journal of Investigational Allergology... Jun 2024
Successful Desensitization to Isatuximab in a Patient With Refractory Multiple Myeloma and Indolent Systemic Mastocytosis. Reply to: Anaphylactic Shock due to Isatuximab and Successful Desensitization.
Topics: Humans; Multiple Myeloma; Anaphylaxis; Mastocytosis, Systemic; Desensitization, Immunologic; Antibodies, Monoclonal, Humanized; Drug Hypersensitivity
PubMed: 38888584
DOI: 10.18176/jiaci.0990 -
Immunity, Inflammation and Disease Jun 2024For decades, studies have demonstrated the anti-inflammatory potential of proteins secreted by helminths in allergies and asthma. Previous studies have demonstrated the...
BACKGROUND
For decades, studies have demonstrated the anti-inflammatory potential of proteins secreted by helminths in allergies and asthma. Previous studies have demonstrated the immunomodulatory capabilities of Succinate Coenzyme A ligase beta-like protein (SUCLA-β) derived from Trichinella spiralis, a crucial excretory product of this parasite.
OBJECTIVE
To explore the therapeutic potential of SUCLA-β in alleviating and controlling ovalbumin (OVA)-induced allergic asthma, as well as its influence on host immune modulation.
METHODS
In this research, we utilized the rTs-SUCLA-β protein derived from T. spiralis to investigate its potential in mitigating airway inflammation in a murine model of asthma induced by OVA sensitization/stimulation, both pre- and post-challenge. The treatment's efficacy was assessed by quantifying the extent of inflammation in the lungs.
RESULTS
Treatment with rTs-SUCLA-β demonstrated efficacy in ameliorating OVA-induced airway inflammation, as evidenced by a reduction in eosinophil infiltration, levels of OVA-specific Immunoglobulin E, interferon-γ, interleukin (IL)-9, and IL-17A, along with an elevation in IL-10. The equilibrium between Th17 and Treg cells plays a pivotal role in modulating the abundance of inflammatory cells within the organism, thereby ameliorating inflammation and alleviating symptoms associated with allergic asthma.
CONCLUSIONS AND CLINICAL RELEVANCE
Our data revealed that T. spiralis-derived Ts-SUCLA-β protein may inhibit the allergic airway inflammation by regulating host immune responses.
Topics: Trichinella spiralis; Animals; Asthma; Mice; Ovalbumin; Helminth Proteins; Mice, Inbred BALB C; Disease Models, Animal; Female; Cytokines; Immunoglobulin E; Lung; T-Lymphocytes, Regulatory; Hypersensitivity; Th17 Cells
PubMed: 38888451
DOI: 10.1002/iid3.1321 -
Cancer Medicine Jun 2024Asparaginase is essential for treating T-cell acute lymphoblastic leukemia (T-ALL). Despite the ongoing debate on whether T-ALL and T-cell lymphoblastic lymphoma (T-LBL)...
BACKGROUND
Asparaginase is essential for treating T-cell acute lymphoblastic leukemia (T-ALL). Despite the ongoing debate on whether T-ALL and T-cell lymphoblastic lymphoma (T-LBL) are the same disease entity or two distinct diseases, patients with T-LBL often receive the same or similar treatment protocols as those with T-ALL.
METHODS
The outcomes of patients with or without L-asparaginase discontinuation were retrospectively analyzed among four national protocols: Japan Association of Childhood Leukemia Study (JACLS) ALL-02 and ALL-97 for T-ALL and Japanese Pediatric Leukemia/Lymphoma Study Group ALB-NHL03 and JACLS NHL-98 for T-LBL. The hazard ratio (HR) was calculated with the Cox regression model by considering L-asparaginase discontinuation as a time-dependent variable.
RESULTS
In total, 199 patients with T-ALL, and 133 patients with T-LBL were included. L-asparaginase discontinuation compromised event-free survival (EFS) of T-ALL patients (ALL-02: HR 3.32, 95% confidence interval [CI] 1.40-7.90; ALL-97: HR 3.39, 95%CI 1.19-9.67). Conversely, EFS compromise was not detected among T-LBL patients (ALB-NHL03: HR 1.39, 95%CI 0.41-4.68; NHL-98: HR 0.92, 95%CI 0.11-7.60).
CONCLUSION
The effects of L-asparaginase discontinuation differed between T-ALL and T-LBL. We assume that the differential impact results from (1) the inherent differential response to L-asparaginase between them and/or (2) a less stringent assessment of early treatment response in T-LBL than in T-ALL. Given the poor salvage rate of refractory or relapsed T-ALL and T-LBL, optimization of the frontline therapy is critical, and the current study provides a new suggestion for further treatment modifications. However, larger studies in contemporary intensified treatment protocols are required.
Topics: Humans; Asparaginase; Child; Male; Female; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; Child, Preschool; Retrospective Studies; Adolescent; Infant; Treatment Outcome; Antineoplastic Combined Chemotherapy Protocols; Japan; Antineoplastic Agents
PubMed: 38888368
DOI: 10.1002/cam4.7246 -
Investigative Ophthalmology & Visual... Jun 2024The current study evaluated the lid margin microbiome of keratinized lid margins of patients with chronic Stevens-Johnson syndrome (SJS) and compared it with healthy...
PURPOSE
The current study evaluated the lid margin microbiome of keratinized lid margins of patients with chronic Stevens-Johnson syndrome (SJS) and compared it with healthy controls and historically reported lid margin microbiome of patients with meibomian gland dysfunction (MGD).
METHODS
Eyelid margin swabs of 20 asymptomatic adults (mean age = 29 ± 12 years) and 10 patients with chronic SJS (mean age = 31.2 ± 14 years) with lid margin keratinization were sequenced using next generation of 16S rDNA V3 to V4 variable region. Within SJS, the keratinized lid margin microbiome was compared with adjacent eyelid skin.
RESULTS
All patients had obstructive MGD, and mean Schirmer I value was 2.8 ± 1.9 mm. The phyla were similar in two groups, whereas at the genera level, an increase in the relative abundance of Corynebacterium, Haemophilus, Azotobacter, and Afipia and a decrease of Acinetobacter was noted in SJS compared to healthy lid margins. SJS-associated microbiota displayed lesser diversity and more heterogeneity than healthy controls. The Principal Components Analysis (PCA) plot revealed wide separation in the SJS and the control groups. Correlational network analysis revealed Corynebacterium and Sphingomonas forming a major hub of negative interactions with other bacterial genera in the SJS group. Significant differences exist in the prevalent genera between keratinized lid margins and historically reported meibum microbiome of patients with MGD. In addition, the eyelid skin of patients with SJS had predominant Staphylococcus, whereas Corynebacterium and Pseudomonas were more in the keratinized lid margins compared to the eyelid skin microbiome.
CONCLUSIONS
Lid margin microbiome is significantly altered in the keratinized lid margins of patients with SJS compared to the eyelid skin of patients with SJS, normal lid margins, and patients with MGD.
Topics: Humans; Male; Female; Adult; Microbiota; Dry Eye Syndromes; Eyelids; Stevens-Johnson Syndrome; Middle Aged; Young Adult; Bacteria; RNA, Ribosomal, 16S; DNA, Bacterial; Adolescent; Meibomian Glands; Meibomian Gland Dysfunction; Keratins
PubMed: 38888283
DOI: 10.1167/iovs.65.6.28 -
Skin Research and Technology : Official... Jun 2024The total glucoside of paeony (TGP) is recognized for its immunomodulatory properties and anti-inflammatory effects. This study evaluates the efficacy of TGP combined...
BACKGROUND
The total glucoside of paeony (TGP) is recognized for its immunomodulatory properties and anti-inflammatory effects. This study evaluates the efficacy of TGP combined with oral mini-pulse therapy (OMP) and narrow-band ultraviolet B (NB-UVB) in treating active nonsegmental vitiligo (NSV).
MATERIALS AND METHODS
The combination therapy was contrasted against those from a group treated solely with OMP and NB-UVB. Data from 62 patients undergoing TGP combination treatment and 55 without were analyzed over a 3-month period. After 6 months, the differences in recurrence rate were investigated by follow-up.
RESULTS
The findings indicate that integrating TGP may yield superior outcomes compared to OMP + NB-UVB alone. Moreover, the patient's oxidative stress makers were significantly reduced after the treatment. The majority of patients in the TGP cohort exhibited enhanced skin pigmentation over the duration. Notably, no increase in side effects or recurrence was observed in this group. Especially, patients with vitiligo on their head and neck experienced pronounced improvements.
CONCLUSION
The efficacy of the combination treatment group was better than that of the control group at 2 and 3 months, and there was no difference in recurrence rate and side effects, suggesting that TGP may continue to show efficacy in NSV for a longer period of time by reducing the level of oxidative stress, and is especially suitable for patients with head and neck lesions.
Topics: Humans; Vitiligo; Female; Male; Adult; Ultraviolet Therapy; Retrospective Studies; Paeonia; Glucosides; Combined Modality Therapy; Middle Aged; Young Adult; Adrenal Cortex Hormones; Treatment Outcome; Administration, Oral; Plant Extracts; Adolescent; Skin Pigmentation
PubMed: 38887837
DOI: 10.1111/srt.13769 -
Frontiers in Immunology 2024The assessment of tuberculosis (TB) treatment outcomes predominantly relies on sputum culture conversion status. To enhance treatment management, it is crucial to...
INTRODUCTION
The assessment of tuberculosis (TB) treatment outcomes predominantly relies on sputum culture conversion status. To enhance treatment management, it is crucial to identify non-sputum-based biomarkers that can predict unfavorable outcomes. Cytokines are widely studied as diagnostic biomarkers for active TB. However, their potential as indicators for unfavorable treatment outcomes remains uncertain.
METHODOLOGY
This study was conducted within a well-characterized cohort comprising newly diagnosed patients with drug-sensitive pulmonary TB, confirmed through sputum smear and culture positivity. Our objective was to elucidate the TB antigen-stimulated cytokine profile at pre-treatment and at 2 months into anti-TB treatment (ATT) in patients with unfavorable treatment outcomes (cases, = 27) in comparison to recurrence-free, microbiologically cured controls ( = 31). Whole blood was stimulated with TB antigens using the QuantiFERON In-tube gold method, and plasma supernatants were subjected to a panel of 14 cytokine measurements.
RESULTS
In our study, pre-treatment analysis revealed that eight cytokines (IL-2, IFN-γ, TNF-α, IL-6, IL-10, IL-17A, IL-18, and GM-CSF) were significantly elevated at baseline in cases compared to cured controls, both in unstimulated conditions and following TB antigen (CFP10, ESAT6, and TB7.7) stimulation. A similar pattern was observed at the 2-month mark of ATT, with eight cytokines (IL-2, IL-10, IL-13, IFN-γ, IL-6, IL-12p70, IL-17A, and TNF-α) showing significant differences between the groups. Importantly, no variations were detected following mitogen stimulation, underscoring that these distinctive immune responses are primarily driven by TB-specific antigens.
CONCLUSION
Our findings indicate that individuals with unfavorable TB treatment outcomes display a characteristic cytokine profile distinct from TB-cured patients, even before commencing ATT. Therefore, the levels of specific cytokine pre-treatment and at the 2-month point in the course of treatment may serve as predictive immune markers for identifying individuals at risk of unfavorable TB treatment outcomes, with these responses being predominantly influenced by TB-specific antigens.
Topics: Humans; Tuberculosis, Pulmonary; Cytokines; Male; Female; Adult; Middle Aged; Biomarkers; Antigens, Bacterial; Treatment Outcome; Antitubercular Agents; Mycobacterium tuberculosis; Aged
PubMed: 38887283
DOI: 10.3389/fimmu.2024.1392256 -
Scientific Reports Jun 2024This split-mouth blinded randomized controlled study compared the efficacy of a desensitizing agent with oxalate/resin polymer and a universal adhesive containing... (Randomized Controlled Trial)
Randomized Controlled Trial
Desensitizing efficacy of a universal dentin adhesive containing mesoporous bioactive glass on dentin hypersensitivity: a randomized clinical trial with a split-mouth model.
This split-mouth blinded randomized controlled study compared the efficacy of a desensitizing agent with oxalate/resin polymer and a universal adhesive containing mesoporous bioactive glass (MBG) for dentin hypersensitivity (DH) relief, using Schiff sensitivity score (SSS) and visual analog scale (VAS). Split quadrants containing teeth with DH were treated with either MS Coat ONE or Hi-Bond Universal with MBG as the functional additive. Assessments at baseline, immediately post-application, and at 1- and 2-week follow-ups used standardized stimulus protocols (air, cold, and acid). The SSS difference was the primary outcome, while the VAS difference was the secondary outcome. A mixed linear effect model performed statistical analysis. Immediate DH reduction occurred in response to air stimuli, with a significant decrease in Group HB than in Group MS (p = 0.0178). Cold stimulus reduction exhibited a gradual cumulative effect, with consistently greater reductions in Group HB than in Group MS (p ≤ 0.0377). Both groups effectively managed acidic stimuli, with no significant differences (p > 0.05). The VAS scores decreased gradually over the follow-up period (p < 0.0001). This study highlights the differential efficacy of treatments for various DH triggers and recommends specific approaches based on different stimulus types. The universal adhesive containing MBG demonstrated DH relief potential, promising efficacy identical to or superior to that of a dedicated desensitizing agent. Further research exploring the long-term efficacy and underlying mechanisms is warranted. The universal adhesive containing MBG can be adopted as an in-office desensitizing agent for DH relief. The desensitizing efficacy of universal adhesive matches or surpasses dedicated agents for air and cold stimuli.
Topics: Humans; Dentin Sensitivity; Female; Male; Dentin Desensitizing Agents; Adult; Glass; Treatment Outcome; Ceramics; Dental Cements; Young Adult; Middle Aged; Porosity
PubMed: 38886498
DOI: 10.1038/s41598-024-64404-x -
Scientific Reports Jun 2024The complexity of systemic lupus erythematosus (SLE) arises from intricate genetic and environmental interactions, with STING playing a pivotal role. This study aims to...
The complexity of systemic lupus erythematosus (SLE) arises from intricate genetic and environmental interactions, with STING playing a pivotal role. This study aims to comprehend the function of STING using the pristane-induced lupus (PIL) model in Sting missense mutant mice (Goldenticket or Sting), which contrasts with previous research using Sting knockout mice. Investigating two-month-old Sting mice over six months post-PIL induction, we observed a profound reduction in autoimmune markers, including antinuclear and anti-dsDNA antibodies, germinal center B cells, and plasma cells, compared to their wild-type counterparts. A pivotal finding was the marked decrease in IL-17-producing T cells. Notably, the severity of lupus nephritis and pulmonary hemorrhages was significantly diminished in Sting mice. These findings demonstrate that different genetic approaches to interfere with STING signaling can lead to contrasting outcomes in SLE pathogenesis, which highlights the need for a nuanced understanding of the role of STING in drug development for SLE. In summary, the loss of Sting function in Goldenticket mutant mice rescued autoimmune phenotypes in PIL. This study reveals the critical nature of STING in SLE, suggesting that the method of STING modulation significantly influences disease phenotypes and should be a key consideration in developing targeted therapies.
Topics: Animals; Mice; Lupus Erythematosus, Systemic; Membrane Proteins; Disease Models, Animal; Antibodies, Antinuclear; Terpenes; Female; Interleukin-17; Lupus Nephritis; Mutation, Missense; B-Lymphocytes
PubMed: 38886451
DOI: 10.1038/s41598-024-64495-6 -
Nature Communications Jun 2024Efficient utilization of nutrients is crucial for microbial survival and virulence. The same nutrient may be utilized by multiple catabolic pathways, indicating that the...
Efficient utilization of nutrients is crucial for microbial survival and virulence. The same nutrient may be utilized by multiple catabolic pathways, indicating that the physical and chemical environments for induction as well as their functional roles may differ. Here, we study the tagatose and Leloir pathways for galactose catabolism of the human pathogen Streptococcus pneumoniae. We show that galactose utilization potentiates pneumococcal virulence, the induction of galactose catabolic pathways is influenced differentially by the concentration of galactose and temperature, and sialic acid downregulates galactose catabolism. Furthermore, the genetic regulation and in vivo induction of each pathway differ, and both galactose catabolic pathways can be turned off with a galactose analogue in a substrate-specific manner, indicating that galactose catabolic pathways can be potential drug targets.
Topics: Streptococcus pneumoniae; Galactose; Gene Expression Regulation, Bacterial; Virulence; Animals; Hexoses; Mice; Metabolic Networks and Pathways; Humans; Pneumococcal Infections; N-Acetylneuraminic Acid; Temperature; Bacterial Proteins; Female
PubMed: 38886409
DOI: 10.1038/s41467-024-49619-w -
RMD Open Jun 2024To compare longitudinal changes in spirometric measures between patients with rheumatoid arthritis (RA) and non-RA comparators.
OBJECTIVE
To compare longitudinal changes in spirometric measures between patients with rheumatoid arthritis (RA) and non-RA comparators.
METHODS
We analysed longitudinal data from two prospective cohorts: the UK Biobank and COPDGene. Spirometry was conducted at baseline and a second visit after 5-7 years. RA was identified based on self-report and disease-modifying antirheumatic drug use; non-RA comparators reported neither. The primary outcomes were annual changes in the per cent-predicted forced expiratory volume in 1 s (FEV%) and per cent predicted forced vital capacity (FVC%). Statistical comparisons were performed using multivariable linear regression. The analysis was stratified based on baseline smoking status and the presence of obstructive pattern (FEV/FVC <0.7).
RESULTS
Among participants who underwent baseline and follow-up spirometry, we identified 233 patients with RA and 37 735 non-RA comparators. Among never-smoking participants without an obstructive pattern, RA was significantly associated with more FEV% decline (β=-0.49, p=0.04). However, in ever smokers with ≥10 pack-years, those with RA exhibited significantly less FEV% decline than non-RA comparators (β=0.50, p=0.02). This difference was more pronounced among those with an obstructive pattern at baseline (β=1.12, p=0.01). Results were similar for FEV/FVC decline. No difference was observed in the annual FVC% change in RA versus non-RA.
CONCLUSIONS
Smokers with RA, especially those with baseline obstructive spirometric patterns, experienced lower FEV% and FEV/FVC decline than non-RA comparators. Conversely, never smokers with RA had more FEV% decline than non-RA comparators. Future studies should investigate potential treatments and the pathogenesis of obstructive lung diseases in smokers with RA.
Topics: Humans; Arthritis, Rheumatoid; Male; Spirometry; Female; Middle Aged; Longitudinal Studies; Prospective Studies; Smoking; Aged; Forced Expiratory Volume; Vital Capacity; Pulmonary Disease, Chronic Obstructive; Adult; United Kingdom
PubMed: 38886003
DOI: 10.1136/rmdopen-2024-004281