Autoimmune lymphoproliferative syndrome (ALPS) is a primary immunodeficiency caused by impaired Fas/FasL-mediated apoptosis of lymphocytes and is characterized by chronic nonmalignant or benign lymphoproliferation, autoimmune manifestations and expansion of double negative (DN) T-cells (TCRαβ+CD4-CD8-). Most cases of ALPS are associated with germline (ALPS-FAS) or somatic (ALPS-sFAS) heterozygous FAS mutations or a combination of both. Here we report three unrelated patients with ALPS-sFAS. Only one of them showed impaired Fas function in PHA-activated T-cells. In this patient, the genetic analysis of the caspase-10 gene (CASP10) identified a heterozygous germline change in exon 9 (c.1337A>G) causing Y446C substitution in the caspase-10 protein. In addition, this patient had a dysregulated T- and B-cell phenotype; circulating lymphocytes showed expansion of T effector memory CD45RA+ (TEMRA) CD4 T-cells, effector memory CD8 T-cells, CD21(low) B-cells and reduced memory switched B-cells. Additionally, this patient showed altered expression in T-cells of several molecules that change during differentiation from naïve to effector cells (CD27, CD95, CD57 and perforin). Molecular alterations in genes of the Fas pathway are necessary for the development of ALPS and this syndrome could be influenced by the concurrent effect of other mutations hitting different genes involved in Fas or related pathways.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.imbio.2015.08.004 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Introduction: Primary immunodeficiency diseases (PIDs), are a growing group of rarely seen diseases. Various clinical conditions like autoimmunity, lymphoproliferative/malignant diseases, chronic lung and gastrointestinal system diseases have been identified which accompanies PIDs besides recurrent infections. However, there is a lack of information about accompanying cardiovascular diseases.
View Article and Find Full Text PDFDistinct subtypes of post-transplant lymphoproliferative disorders: CHIP-like mutations in early lesions and substantial mutational differences between EBV-positive and EBV-negative diffuse large B-cell lymphomas.
Br J Haematol
January 2025
Pathology, Institute of Medical Genetics and Pathology, University Hospital Basel, University of Basel, Basel, Switzerland.
Post-transplant lymphoproliferative disorders (PTLD) and lymphomas in immunocompromised individuals represent significant clinical challenges, with a limited understanding of their pathogenesis. We investigated a PTLD cohort (n = 50) consisting of 'early lesions' (infectious mononucleosis-like PTLD, plasmacytic and follicular hyperplasias), polymorphic PTLD and post-transplant diffuse large B-cell lymphomas (PT-DLBCL). The study also included 15 DLBCL with autoimmune/immunocompromised backgrounds (IS-DLBCL) and 14 DLBCL, not otherwise specified (DLBCL, NOS), as control.
View Article and Find Full Text PDFAdvanced whole transcriptome sequencing and artificial intelligence/machine learning (AI/ML) in imiquimod-induced psoriasis-like inflammation of human keratinocytes.
Biomedicine (Taipei)
December 2024
Million-Person Precision Medicine Initiative, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan.
Introduction: Although the HaCaT keratinocyte model has been used in previous research to study the effects of antipsoriatic agents, there is still a lack of comprehensive understanding of the mechanism of imiquimod (IMQ)-induced proliferation and signal transduction in psoriasis-like keratinocytes.
Objectives: This study aimed to investigate the molecular mechanisms and pathways associated with psoriasis-like inflammation caused by IMQ in human keratinocytes.
Materials And Methods: HaCaT cells were exposed to different concentrations of IMQ to induce inflammation similar to that observed in psoriasis.
Angioedema due to acquired C1-inhibitor deficiency without hematological condition: a multicenter French cohort study of 34 patients.
J Allergy Clin Immunol Pract
January 2025
Sorbonne Université, service de médecine interne, AP-HP, Hôpital Saint Antoine, F-75012 Paris, France. Electronic address:
Background: Angioedema (AE) due to acquired C1-inhibitor deficiency (AAE-C1-INH) is a rare disease associating recurrent edema of mucosa and skin. Several underlying diseases have been reported, mainly lymphoproliferative diseases and monoclonal gammopathy. However, 15 to 20% of patients never exhibit such a hematological condition.
View Article and Find Full Text PDFA spectrum of neurological diseases with elevated cerebrospinal fluid adenosine deaminase levels.
J Neurol Sci
December 2024
Department of Neurology, Graduate School of Medicine, Chiba University, Chiba, Japan.
Article Synopsis
- This study investigated how adenosine deaminase (ADA) levels in cerebrospinal fluid (CSF) relate to different neurological disorders.
- Five specific diseases showed significantly higher CSF ADA levels compared to a noninflammatory control group, with tuberculous meningitis (TBM) showing the highest increase.
- Strong positive correlations were found between CSF ADA levels and several other laboratory parameters, suggesting that elevated ADA levels might indicate T-cell hyperactivation in the central nervous system.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!