Publications by authors named "Corentin Le Floc'h"
Outbreaks of chilblains were reported during the COVID-19 pandemic. Given the essential role of type I interferon (I-IFN) in protective immunity against SARS-CoV-2 and the association of chilblains with inherited type I interferonopathies, we hypothesized that excessive I-IFN responses to SARS-CoV-2 might underlie the occurrence of chilblains in this context. We identified a transient I-IFN signature in chilblain lesions, accompanied by an acral infiltration of activated plasmacytoid dendritic cells (pDCs).
View Article and Find Full Text PDFPatients heterozygous for germline CBL loss-of-function (LOF) variants can develop myeloid malignancy, autoinflammation, or both, if some or all of their leukocytes become homozygous for these variants through somatic loss of heterozygosity (LOH) via uniparental isodisomy. We observed an upregulation of the inflammatory gene expression signature in whole blood from these patients, mimicking monogenic inborn errors underlying autoinflammation. Remarkably, these patients had constitutively activated monocytes that secreted 10 to 100 times more inflammatory cytokines than those of healthy individuals and CBL LOF heterozygotes without LOH.
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- * A study examined 131 female patients with X-linked dominant incontinentia pigmenti (IP), finding that 36% produced autoantibodies against IFN-α and/or IFN-ω, significantly higher than age-matched controls.
- * The presence of these autoantibodies is linked to an abnormally small thymus and predisposes patients to life-threatening viral infections, while those without these autoantibodies do not face the same risk.
A sensitive assay for measuring whole-blood responses to type I IFNs.
Proc Natl Acad Sci U S A
October 2024
Article Synopsis
- Inborn errors or autoantibodies (auto-Abs) against type I interferons (IFNs) can lead to severe viral infections.
- Researchers developed a straightforward blood test that can identify these conditions by stimulating blood with glycosylated IFN-α2, -β, or -ω and measuring IP-10 levels.
- The study found that IP-10 levels in patients with inherited deficiencies only increase with type II IFN (IFN-γ), while those with auto-Abs can still respond to non-neutralized type I IFNs.
FMS-related tyrosine kinase 3 ligand (FLT3L), encoded by FLT3LG, is a hematopoietic factor essential for the development of natural killer (NK) cells, B cells, and dendritic cells (DCs) in mice. We describe three humans homozygous for a loss-of-function FLT3LG variant with a history of various recurrent infections, including severe cutaneous warts. The patients' bone marrow (BM) was hypoplastic, with low levels of hematopoietic progenitors, particularly myeloid and B cell precursors.
View Article and Find Full Text PDFWe describe humans with rare biallelic loss-of-function variants impairing pre-α T cell receptor (pre-TCRα) expression. Low circulating naive αβ T cell counts at birth persisted over time, with normal memory αβ and high γδ T cell counts. Their TCRα repertoire was biased, which suggests that noncanonical thymic differentiation pathways can rescue αβ T cell development.
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- The study discusses a rare lung disease in nine children linked to a genetic deficiency of the CCR2 receptor, leading to conditions like pulmonary alveolar proteinosis (PAP) and increased vulnerability to infections.
- This deficiency is characterized by loss-of-function variants, affecting the migration and signaling of immune cells, particularly monocytes, due to a lack of response to CCL-2, a chemokine essential for these processes.
- Elevated levels of CCL-2 in the blood serve as a diagnostic marker for identifying children with unexplained respiratory issues or recurrent infections, indicating the importance of CCR2 in lung health and immune response.