FITC-Labeled Human CD19 (20-291) Protein, Fc Tag DMF

Abstract: Tisagenlecleucel (tisa-cel) and brexucabtagene autoleucel (brexu-cel) are approved CD19 CAR T products for young adults (YAs) with relapsed/refractory B-ALL. A distinct analysis of YAs receiving commercial CD19 CAR T has not been reported. Utilizing retrospective data from the Pediatric Real-World CAR T Consortium and the Real-World Outcomes of CAR T in Adult ALL collaboration, we describe efficacy and safety of tisa-cel and brexu-cel in 70 young adults (18-26 years; tisa-cel: 50, brexu-cel: 20). Cytokine release syndrome (CRS) and immune-effector cell associated neurotoxicity syndrome (ICANS) were observed more frequently for brexu-cel vs tisa-cel (CRS= 85% vs 56%, p=0.01; ICANS= 40% vs 18%, p=0.05). CR rates were similar between products at 80% for brexu-cel and 88% for tisa-cel (p=0.39). Relapse free survival (RFS) at 12 months was 46% for brexu-cel (95% CI 31-81%) and 36% for tisa-cel (95% CI 26-52%, p=0.79). Durability of remission over 12 months was 61% for brexu-cel (95% CI 41-93%) vs 41% for tisa-cel (95% CI 27-61%, p=0.12). 12-month overall survival (OS) for brexu-cel was 84% (95% CI 81-100) vs 68% for tisa-cel (95% CI 56-85, HR 1.9, p=0.35). In multivariate analysis, low disease burden was associated with improved OS (HR 0.23, 95% CI 0.06-0.86, p=0.03), while inotuzumab pre-CAR T was associated with inferior outcomes (OS HR 6.32, 95% CI 1.48-27, p=0.01; RFS HR 3.65, 95% CI 1.41-9.46, p=0.008). This study demonstrates comparable real-world efficacy among young adults receiving CD19 CAR T therapy irrespective of CAR T construct, however, rates of toxicity appear higher with brexu-cel.Copyright © 2025 American Society of Hematology.

Abstract: We aimed to investigate molecular mechanisms affecting melanoma progression by comparing genetic/epigenetic features between melanomas of different Breslow thickness and stage using TCGA (The Cancer Genome Atlas) data. The TCGA, Firehose Legacy, melanoma data set was utilized on the cBioPortal website. The cases were compared in terms of mRNA expression and DNA methylation. Gene Ontology (GO) and KEGG pathways enrichment analysis were performed using the online WebGestalt tool. STRING and Cytoscape software were used to construct a protein-protein interaction network and identify hub genes. P and q<0.05, FDR< 0.05 were considered statistically significant. 1001 differentially expressed genes were identified between thin (≤1 mm) and thick (>1 mm) melanomas. Pathway analyses revealed that genes enriched in thin melanomas were associated with adaptive immune response, T-cell activation, immune response regulation, leukocyte, and cytokine-related pathways, whereas genes enriched in thick melanomas were related to epidermis development. Ten hub genes were identified (CD4, IFNG, PTPRC, CD8A, CTLA4, CD69, ICOS, CD27, CD28, CD19). All of these genes are involved in crucial immunological processes. Understanding the complex changes in melanoma progression is essential for accurate diagnosis and prediction of prognosis. Our results may shed light on subsequent studies to identify the steps in melanoma progression.Copyright © 2025 Wolters Kluwer Health, Inc. All rights reserved.

Abstract: The study aims to assess baseline immune parameters that predict infection risk in autoimmune rheumatic disease (ARD) patients, with the goal of identifying high-risk individuals requiring immunosuppressive therapy escalation, based on infection rates during a one-year follow-up.The independent cohort study was conducted at a tertiary rheumatology center in India from December 2019 to March 2022. It included adult participants with ARDs undergoing immunosuppression. Ethics approval and informed consent were obtained. Patients underwent detailed history, clinical examination, and baseline investigations, which included complete hemogram, inflammatory parameters, immunoglobulin levels, cellular levels of the immune system, complement levels, and viral markers. Descriptive statistics, ANOVA, chi-squared tests, t-tests, and Fisher's exact tests were used. OLS regression analyses identified significant predictors of infection risk. They were followed up for a period of 1 year for any infection episodes.Of the 106 participants recruited, 4 were excluded due to disease-related complications during the 3-month period of follow-up. The mean age of the participants was 38.21 ± 12.73 years, with an average follow-up duration of 13.1 ± 8.35 months. Among the remaining 102 participants, younger age was associated with a lower infection risk (OR 1.047). Protective factors against infection included lower levels of immunoglobulin E (IgE) (OR 0.379), methotrexate (MTX) use (OR 0.247), and biologics (OR 0.543). Conversely, lower Immunoglobulin G (IgG), elevated neutrophil counts (OR 3.588), higher neutrophil-to-lymphocyte ratios (NLR) (OR 2.577), low platelet counts (OR 0.546), and steroid use, which increased the risk fivefold (OR 5.686), were identified as risk factors. Ordinary Least Squares (OLS) regression analysis highlighted age, IgG levels, CD19 lymphocyte counts, WBC counts, and ESR as significant predictors of infection risk between the groups.Older age, low IgG, low B cell count (CD19) predict susceptibility to infections; high neutrophil counts, low platelets, and elevated NLR are key predictors of developing infection in ARDs patients. Careful monitoring and tailored treatment strategies are essential to reduce infection risks. Further research is needed in this direction to develop predictive algorithms.© 2025 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.

Abstract: Membranous nephropathy (MN) and idiopathic nephrotic syndrome (INS) are two B-cell mediated rare glomerular diseases that benefit from treatment with B-cell depleting anti-CD20 monoclonal antibody rituximab. Different B-cell dysregulations have been described in pediatric INS patients and in adults affected by MN. In adult MN patients, an increased level of mature-naïve cells and atypical memory B cells and a significant reduction in IgM memory and switched memory B cells have been previously described compared to healthy individuals. To date, there is no information available about B-cell immunophenotyping in pediatric MN.In this monocentric retrospective case-control study, we analyzed by flow cytometry the B-cell profile in rituximab-naïve (n = 15) children affected by MN, compared with pediatric INS patients (n = 15) selected by propensity score matching, and both evaluated during active disease. Age-matched controls (n = 15) with non-immune-mediated kidney diseases were also characterized. Demographical, clinical, laboratory, and immunosuppressive treatment data were registered.We found that children with MN and INS had significantly higher circulating levels of total CD19+, mature-naïve, and atypical memory B cells and similar levels of transitional B cells when compared to age-matched controls. Circulating levels of total memory B cells, IgM memory B cells, and plasmablasts/plasmacells were significantly higher in INS patients compared to both MN patients and age-matched controls.Our study indicated that children affected by MN had a specific B-cell profile and that high levels of memory B-cell subsets are specific to INS pediatric patients independently of proteinuria intensity.© 2025. The Author(s), under exclusive licence to International Pediatric Nephrology Association.