Publications by authors named "Matthieu Chaldebas"
Article Synopsis
- T follicular helper (Tfh) cells, which are important for antibody production, rely heavily on the immunoreceptor PD-1, and its deficiency leads to weakened Tfh functions and impaired immune responses in mice.
- Individuals lacking PD-1 or PD-L1 demonstrate fewer memory B cells and diminished antibody responses, highlighting the critical role of these molecules in immune system functionality.
- PD-1 influences both the intrinsic and extrinsic aspects of B cell memory and antibody production, suggesting that disruptions in PD-1 signaling can lead to complications in immune responses, especially during anti-PD-1-PD-L1 therapies.
Article Synopsis
- Some babies with a specific mutation in the IL7R gene have a serious immune problem called SCID, where they lack a certain type of immune cells called T cells, but still have normal B and NK cells.
- In a study of 6 adults who have a similar genetic issue, they showed low levels of T cells but had relatively normal levels of other immune cells, indicating a more specific problem in T cell development.
- Even though their T cells didn’t grow well in the lab, the study hints that there might be another way T cells can develop that doesn’t depend solely on the IL-7 cytokine.
Severe defects in human IFNγ immunity predispose individuals to both Bacillus Calmette-Guérin disease and tuberculosis, whereas milder defects predispose only to tuberculosis. Here we report two adults with recurrent pulmonary tuberculosis who are homozygous for a private loss-of-function TNF variant. Neither has any other clinical phenotype and both mount normal clinical and biological inflammatory responses.
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- The study identifies two cases of herpes simplex virus 1 (HSV-1) encephalitis in children linked to rare genetic variants of the TMEFF1 gene, which plays a protective role in the brain.
- TMEFF1 protein interacts with the HSV-1 receptor NECTIN-1, blocking the virus's ability to enter brain cells, but genetic deficiencies in TMEFF1 allow for easier viral entry and replication within neurons.
- The research suggests that enhancing TMEFF1 levels or using type I interferon can restore resistance to HSV-1, indicating a potential therapeutic pathway for preventing HSV-1 encephalitis.
Inherited deficiency of the RNA lariat-debranching enzyme 1 (DBR1) is a rare etiology of brainstem viral encephalitis. The cellular basis of disease and the range of viral predisposition are unclear. We report inherited DBR1 deficiency in a 14-year-old boy who suffered from isolated SARS-CoV-2 brainstem encephalitis.
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- - The text discusses the impact of genetic variants that introduce an AG sequence in the intronic regions of protein-coding genes, which can disrupt pre-mRNA splicing and lead to various diseases.
- - A computational tool called AGAIN was developed to identify these AG-gain variants systematically, uncovering 350 variants that cause splicing alterations, with a significant portion creating new splice sites or causing exon skipping.
- - Applications of AGAIN in patient samples illustrated its efficacy, revealing a specific AG-gain variant linked to a patient's mycobacterial disease and frequent missplicing in high-risk regions of the genome, with the tool being publicly accessible for further research.
Background: We previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in ~ 80% of cases.
Methods: We report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia.
Background: We previously reported inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity in 1-5% of unvaccinated patients with life-threatening COVID-19, and auto-antibodies against type I IFN in another 15-20% of cases.
Methods: We report here a genome-wide rare variant burden association analysis in 3,269 unvaccinated patients with life-threatening COVID-19 (1,301 previously reported and 1,968 new patients), and 1,373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. A quarter of the patients tested had antibodies against type I IFN (234 of 928) and were excluded from the analysis.