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Objectives: B cells have immunoregulatory function acting as antigen-presenting cells. A separate subset of interleukin (IL)-10 producing B cells (Breg) regulating T cell mediated immunity has been identified. In the present study, we investigated the role of Breg in antineutrophil cytoplasmic antibodies-associated vasculitis (AAV).
Methods: 17 healthy controls (HCs) and 41 patients with AAV were enrolled. 30 patients with AAV were in remission. Furthermore, 11 patients with AAV with active disease were studied. Breg were defined as IL-10(+)CD19(+) B cells upon culture with cytosine-phosphate-guanosine oligodeoxynucleotide (CpG ODN) 2006. Next to Breg, CD4(+)CD127(low)CD25(hi)CD39(neg)/CD39(+) regulatory T-cells (Treg), interferon (IFN)γ(+), IL-4(+) and Il-17A(+)T helper cell subsets were determined via flow cytometry.
Results: Patients with active or quiescent disease showed a diminished fraction of Breg as compared with HCs. The frequency of IFNγ(+) T helper cells was negatively associated with Breg in untreated AAV in remission but not in active vasculitis or in HCs. Interestingly, the total Treg population and the CD39(+) Treg subpopulation correlated positively with Breg in inactive patients with AAV.
Conclusions: IL-10 producing B cells are diminished in AAV. Furthermore, Breg might regulate Th1 cells and are associated with Treg in quiescent AAV. Suppression of Th1 cells by Breg may be insufficient in active AAV.
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http://dx.doi.org/10.1136/annrheumdis-2012-202986 | DOI Listing |
Prog Retin Eye Res
March 2025
Nuffield Laboratory of Ophthalmology, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK; Oxford University Hospitals NHS Foundation Trust, Oxford, UK; Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK. Electronic address:
Retinal gene therapy using adeno-associated viral (AAV) vectors has been a groundbreaking step-change in the treatment of inherited retinal diseases (IRDs) and could also be used to treat more common retinal diseases such as age-related macular degeneration and diabetic retinopathy. The delivery and expression of therapeutic transgenes in the eye is limited by innate and adaptive immune responses against components of the vector product, which has been termed gene therapy-associated uveitis (GTAU). This is clinically important as intraocular inflammation could lead to irreversible loss of retinal cells, deterioration of visual function and reduced durability of treatment effect associated with a costly one-off treatment.
View Article and Find Full Text PDFCancer Cell
March 2025
UNC Lineberger Comprehensive Cancer Center, UNC Health Care System, Chapel Hill, NC, USA. Electronic address:
We leverage a clinical trial (NCT04080804) that compared neoadjuvant anti-PD-1, anti-PD-1+CTLA-4, and anti-PD-1+LAG-3 therapies in head and neck squamous cell carcinoma patients. Combination therapies promote higher pathologic response rates versus monotherapy, and major pathologic response is associated with better survival. To address whether successful immune checkpoint inhibitor (ICI) regimens act through similar or distinct pathways, we robustly and longitudinally characterize transcriptional and proteomic dynamics of CD8 tumor-infiltrating lymphocytes (TILs) in a clonal manner.
View Article and Find Full Text PDFCell Syst
March 2025
Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Electronic address:
Direct conversion generates patient-specific, disease-relevant cell types, such as neurons, that are rare, limited, or difficult to isolate from common and easily accessible cells, such as skin cells. However, low rates of direct conversion and complex protocols limit scalability and, thus, the potential of cell-fate conversion for biomedical applications. Here, we optimize the conversion protocol by examining process parameters, including transcript design; delivery via adeno-associated virus (AAV), retrovirus, and lentivirus; cell seeding density; and the impact of media conditions.
View Article and Find Full Text PDFAm J Cancer Res
February 2025
Department of Clinical Laboratory, Peking University First Hospital Beijing 100034, China.
Gastrin-releasing peptide precursor (ProGRP) is a bioactive precursor of GRP and might play an important role as an emerging tumor marker in early cancer diagnosis. It might also be abnormal in the nonmalignant disease and renal function abnormalities. The present study was undertaken to investigate the changes of ProGRP levels in patients with kidney injuries, especially with chronic kidney disease (CKD), determine the upper reference intervals and clinical diagnostic value of ProGRP in CKD, and thus help oncologists in interpreting ProGRP levels and making clinical judgments of malignances.
View Article and Find Full Text PDFMol Ther Nucleic Acids
March 2025
Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Carbamoyl phosphate synthetase 1 (CPS1) deficiency, a urea-cycle disorder, results in hyperammonemia initiating a sequence of adverse events that can lead to coma and death if not treated rapidly. There is a high unmet need for an effective therapeutic for this disorder, especially in early neonatal patients where mortality is excessive. However, development of an adeno-associated virus (AAV)-based approach is hampered by large cDNA size and high protein requirement.
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