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One hundred thirty-four germ line PU.1 variants and the agammaglobulinemic patients carrying them.

Blood

January 2025

Division of Immunology and Allergy, Children's Hospital of Philadelphia; Department of Pediatrics, Perelman School of Medicine; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States.

Leukopoiesis is lethally arrested in mice lacking the master transcriptional regulator PU.1. Depending on the animal model, subtotal PU.

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Background: Sepsis and acute respiratory distress syndrome (ARDS) are common inflammatory conditions in intensive care, with ARDS significantly increasing mortality in septic patients. PANoptosis, a newly discovered form of programmed cell death involving multiple cell death pathways, plays a critical role in inflammatory diseases. This study aims to elucidate the PANoptosis-related genes (PRGs) and their involvement in the progression of sepsis to ARDS.

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The Anti-Human P2X7 Monoclonal Antibody (Clone L4) Can Mediate Complement-Dependent Cytotoxicity of Human Leukocytes.

Eur J Immunol

January 2025

Molecular Horizons and School of Chemistry and Molecular Bioscience, University of Wollongong, Wollongong, Australia.

P2X7 is an extracellular adenosine 5'-triphosphate (ATP)-gated cation channel that plays various roles in inflammation and immunity. P2X7 is present on peripheral blood monocytes, dendritic cells (DCs), and innate and adaptive lymphocytes. The anti-human P2X7 monoclonal antibody (mAb; clone L4), used for immunolabelling P2X7 or blocking P2X7 activity, is a murine IgG2 antibody, but its ability to mediate complement-dependent cytotoxicity (CDC) is unknown.

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Over the last 50 years, contribution of the immune system has been identified in the development of hypertension and renal injury. Both human and experimental animal models of hypertension have demonstrated that innate and adaptive immune cells, along with their cytokines and chemokines, modulate blood pressure fluctuations and end organ renal damage. Numerous cell types of the innate immune system, specifically monocytes, macrophages, and dendritic cells present antigenic peptides to T cells promoting inflammation and the elevation of blood pressure.

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Testing for PD-L1 expression by immunohistochemistry (IHC) is used to predict immune checkpoint blockade (ICB) benefit but has performed inconsistently in urothelial cancer (UC) clinical trials. Different approaches are used for PD-L1 IHC. We analyzed paired PD-L1 IHC data on UC samples using the SP142 and 22C3 assays from the phase 3 IMvigor130 trial and found discordant findings summarized by four phenotypes: PD-L1 positive by both assays (PD-L1 double positive; PD-L1DP), PD-L1 positive by the SP142 assay only (SP142 single positive; SP142SP), PD-L1 positive by the 22C3 assay only (22C3 single positive; 22C3SP), and PD-L1 negative by both assays double negative (PD-L1 double negative; PD-L1DN).

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