Background: Mutations in the gene for the signal transducer and activator of transcription 1, STAT1, have been shown to be associated with death at an early age due to overwhelming viral infection (complete STAT1 deficiency) or, more commonly, selective deficiencies to mycobacterial or fungal infection (typically heterozygous STAT1 mutations).
Objectives: To define the molecular basis of progressive combined immunodeficiency in a group of patients with fatal infections.
Methods: We studied a group of unrelated patients who displayed an unusual progressive form of combined immunodeficiency. Whole exome sequencing assisted in confirming a common genetic defect in this group, which consisted of a heterozygous mutation of the STAT1 gene. STAT1 protein level as well as function was assessed, and a detailed evaluation of the immune system, including analysis of thymus tissue, was performed.
Results: Patients were found to carry de novo heterozygous mutations in STAT1 encoding T385A, I294T, or C284R amino acid substitutions. STAT1 expression appeared significantly decreased as a result of these changes but not completely absent, with diminished signaling responses. This group display progressive loss in lymphocyte number and function accompanied by increasing autoimmune features as well as severe, fatal infections.
Conclusions: These findings show that some heterozygous aberrations of STAT1 can be associated with progressive combined immunodeficiency, quite distinct from the limited susceptibilities to infection previously reported for heterozygous STAT1 mutations. These mutations were not inherited, rather, arose de novo in each case. Accompanied by significant patient mortality, this finding suggests that this class of STAT1 mutation is ultimately fatal due to overwhelming infection.
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http://dx.doi.org/10.1016/j.jaci.2013.09.032 | DOI Listing |
Turk Arch Pediatr
January 2025
Division of Allergy and Immunology, Department of Pediatrics, Marmara University Faculty of Medicine, İstanbul, Türkiye.
Objective: Prolidase deficiency is a metabolic and immunological disorder that is inherited in an autosomal recessive manner. In prolidase deficiency, a broad spectrum of differences is observed in patients, ranging from asymptomatic to multisystem involvement. There is scarce information in the literature on the atypical features and immunophenotypes of this disease.
View Article and Find Full Text PDFJAAD Case Rep
January 2025
Department of Resuscitation and Neonatal Medicine, Farhat Hached University Hospital, Sousse, Tunisia.
Data Brief
February 2025
Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto M5S 3M2, Canada.
Tenofovir alafenamide (TAF) is currently administered orally to patients for treatment of chronic hepatitis B virus infection and as a part of a combination therapy for human immunodeficiency virus (HIV) infection. A long-acting delivery system could provide several advantages as a formulation strategy for this drug including improved patient adherence, convenience, more consistent drug levels and potentially fewer side effects. To date, the vast majority of polymer-based long-acting delivery systems have been prepared from poly(lactide--glycolide) [1].
View Article and Find Full Text PDFEur J Pharmacol
January 2025
Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran; Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education Research Network (USERN), Tehran, Iran. Electronic address:
The interaction between a cluster of differentiation 47 (CD47) on cancer cells and signal regulatory protein alpha (SIRPα) on macrophages is thought to hinder macrophage phagocytic activity, which can be blocked by combining siRNAs targeting SIRPα (siSIRPα) with simultaneous involvement of activating receptors like FcRs (Fc receptors) anti-programmed death-ligand 1 (anti-PD-L1). For this study, M1 macrophage-derived exosomes were used to deliver the siRNAs, isolated from lipopolysaccharide (LPS)-stimulated RAW264.7 cells and electroporated with siSIRPα.
View Article and Find Full Text PDFClin Gastroenterol Hepatol
January 2025
Inflammatory Bowel Disease Center, Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville FL. Electronic address:
Description: The aim of this American Gastroenterological Association (AGA) Clinical Practice Update (CPU) is to provide best practice advice (BPA) statements for gastroenterologists and other health care providers who provide care to patients with inflammatory bowel disease (IBD). The focus is on IBD-specific screenings (excluding colorectal cancer screening, which is discussed separately) and vaccinations. We provide guidance to ensure that patients are up to date with the disease-specific cancer screenings, vaccinations, as well as advice for mental health and general wellbeing.
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