Effects of polymorphisms in TNFA and TNFR2 on the outcome of 462 cases of unrelated bone marrow transplantation (uBMT) were studied retrospectively. Four alleles of TNFA (U01-U04) distinguished by polymorphism in the upstream region, -1031 (T/C), -863 (C/A) and -857 (C/T), and two alleles of TNFR2 (196M/196R) distinguished by polymorphism at codon 196 were determined. Transplantation involving TNFA-U02- and/or U03-positive donors and/or recipients resulted in a higher incidence of graft-versus-host disease (GVHD) of grade III-IV (P < 0.05 for donor type, P < 0.01 for recipient type) and a lower relapse rate than that involving TNFA-U01 homozygous recipients and/or donors (P < 0.025 for donor type, P < 0.01 for recipient type). These results include the HLA mismatching effect due to linkage disequilibirium of TNFA with HLA loci. However, the effects were also observed in HLA-A, -B and -DRB1 allele-matched transplantation. Transplantation from TNFR2-196R-positive donors exhibited a higher incidence of severe GVHD (P < 0.05) and tendency for a lower relapse rate than that from TNFR2-196M homozygous donors. TNFR2-196R of recipient origin had no effect on GVHD but increased the relapse rate (P < 0.025). These results suggest that TNFA and TNFR2 typings are helpful for predicting uBMT outcome and for preventing severe complications at an early stage.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1038/sj.bmt.1703409 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
TRAF2 and RIPK1 redundantly mediate classical NFκB signaling by TNFR1 and CD95-type death receptors.
Cell Death Dis
January 2025
Division of Molecular Internal Medicine, Department of Internal Medicine II, University Hospital Würzburg, Auvera Haus Grombühlstraße 12, 97080, Würzburg, Germany.
This study suggests a modified model of TNFR1-induced complex I-mediated NFκB signaling. Evaluation of a panel of five tumor cell lines (HCT116-PIK3CAmut, SK-MEL-23, HeLa-RIPK3, HT29, D10) with TRAF2 knockout revealed in two cell lines (HT29, HeLa-RIPK3) a sensitizing effect for death receptor-induced necroptosis and in one cell line (D10) a mild sensitization for TNFR1-induced apoptosis. TRAF2 deficiency inhibited death receptor-induced classical NFκB-mediated production of IL-8 only in a subset of cell lines and only partly.
View Article and Find Full Text PDFNeurotrophomodulatory effect of TNF-α through NF-κB in rat cortical astrocytes.
Cytotechnology
February 2025
Division of Neurobiology, Department of Zoology, The Maharaja Sayajirao University of Baroda, Vadodara, Gujarat India.
Tumor necrosis factor alpha (TNF-α) is a well-known pro-inflammatory cytokine originally recognized for its ability to induce apoptosis and cell death. However, recent research has revealed that TNF-α also plays a crucial role as a mediator of cell survival, influencing a wide range of cellular functions. The signaling of TNF-α is mediated through two distinct receptors, TNFR1 and TNFR2, which trigger various intracellular pathways, including NF-κB, JNK, and caspase signaling cascades.
View Article and Find Full Text PDFTranscriptional Activity of Tumor Necrosis Factor Alpha Genes and Their Receptors in Patients with Varying Degrees of Coronary Artery Disease.
Int J Mol Sci
December 2024
Department of Cardiology, Faculty of Health Sciences in Katowice, Medical University of Silesia in Katowice, 40-635 Katowice, Poland.
Coronary artery disease and its complications are one of the most common causes of morbidity and death worldwide. The aims of this study were to assess the transcriptional activity of the studied TNF-α genes and their receptors in patients with various degrees of coronary artery disease and in the control group, as well as to attempt to link it with the size of the left ventricular ejection fraction and the number of diseased coronary arteries. Taking into account the inclusion and exclusion criteria, a total of 240 people (100%) qualified for this study.
View Article and Find Full Text PDFTNF signaling mediates lipopolysaccharide-induced lung epithelial progenitor cell responses in mouse lung organoids.
Biomed Pharmacother
December 2024
Department of Molecular Pharmacology, University of Groningen, Groningen, Netherlands; Groningen Research Institute for Asthma and COPD (GRIAC), University Medical Center Groningen, University of Groningen, Groningen, Netherlands. Electronic address:
Bacterial respiratory infections are a major global health concern, often leading to lung injury and triggering lung repair mechanisms. Endogenous epithelial progenitor cells are crucial in this repair, yet the mechanisms remain poorly understood. This study investigates the response of lung epithelial progenitor cells to injury induced by lipopolysaccharide (LPS), a component of gram-negative bacteria, focusing on their regulation during lung repair.
View Article and Find Full Text PDFChronic Inflammation Deters Natural Killer Cell Fitness and Cytotoxicity in Myeloid Leukemia.
Blood Adv
November 2024
The University of Alabama at Birmingham, Birmingham, Alabama, United States.
Article Synopsis
- Natural killer (NK) cells are crucial for combating myeloid malignancies, and their function is linked to extended remission in chronic myeloid leukemia (CML), but they experience suppression during the disease.
- Research using a CML mouse model revealed that NK cells have reduced numbers, an immature state, and decreased ability to kill cancer cells, which can improve when the BCR::ABL1 protein is inhibited.
- The study found that inflammatory signals in the CML environment, particularly from TNFa, impair NK cell function, indicating that targeting inflammatory pathways could improve NK cell therapies for CML patients.
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!