Charline Miot’s research while affiliated with University of Angers and other places

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Publications (28)


Childhood Humoral Immunity During and After COVID-19 Lockdowns
  • Article

May 2025

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3 Reads

The Pediatric Infectious Disease Journal

Coralie Mallebranche

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Charline Miot

Our study, including serum from 3678 hospital inpatients and outpatients sampled before, during and after the COVID-19 lockdown periods, showed a significant decrease in overall IgG levels during the periods of sanitary restriction, particularly in children 3–10 years of age. Few months after the lifting of COVID-19 restrictions, immunoglobulin levels normalized. COVID-19 lockdowns may have induced a transient humoral immune gap.



MAGT1 deficiency in XMEN disease is associated with severe platelet dysfunction and impaired platelet glycoprotein N-glycosylation

May 2023

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66 Reads

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8 Citations

Journal of Thrombosis and Haemostasis

Background: X-Linked immunodeficiency with magnesium defect, Epstein-Barr virus infection and neoplasia (XMEN) disease is a primary immunodeficiency due to loss-of-function mutations in the gene encoding for the magnesium transporter 1 (MAGT1). Furthermore, as MAGT1 is involved in the N-glycosylation process, XMEN disease is classified as a Congenital Disorder of Glycosylation. Although XMEN-associated immunodeficiency is well described, the mechanisms underlying platelet dysfunction and responsible for life-threatening bleeding events have never been investigated. Objectives: To assess platelet functions in XMEN patients. Patients/methods: Two unrelated young boys, including one before and after hematopoietic stem-cell transplantation (HSCT), were investigated for their platelet functions, glycoprotein expression, and serum and platelet-derived N-glycans. Results: Platelet analysis highlighted abnormal elongated cells and unusual barbell-shaped proplatelets. Platelet aggregation, integrin αIIbβ3 activation, calcium mobilization and protein kinase C (PKC) activity were impaired in both patients. Strikingly, platelet responses to protease-activated receptor 1 activating peptide (PAR1-AP) were absent at both low and high concentrations. These defects were also associated with decreased molecular weight of glycoprotein (GP)Ibα, GPVI and integrin αIIb due to a partial impairment of N-glycosylation. All these defects were corrected after HSCT. Conclusions: Our results highlight prominent platelet dysfunction related to MAGT1 deficiency and a defective N-glycosylation in several platelet proteins, that could explain the hemorrhages reported in XMEN patients.


Identification of novel compound heterozygous variants in the SLC30A7 (ZNT7) gene in two French brothers with stunted growth, testicular hypoplasia, and bone marrow failure

February 2023

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24 Reads

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6 Citations

Human Molecular Genetics

Zinc is an essential trace mineral. Dietary zinc deficiency results in stunted growth, skin lesions, hypogonadism, and frequent infections in humans. Mice genetically lacking Slc30a7 suffer from mild zinc deficiency and are prone to development of prostate cancer and insulin resistance. Disease-causing variants or mutations in the human SLC30A7 (ZNT7) gene have not been previously reported. Here we describe two-boy siblings from a French family with stunted growth, testicular hypoplasia, and bone marrow failure. Exome sequencing revealed compound heterozygous variants in ZNT7 consisting of NM_133496.5:c.21dup; p.Asp8ArgfsTer3 and c.842 + 15 T > C inherited from their unaffected mother and father, respectively. The c.21dup variant led to a premature stop codon generated in exon 1 of the ZNT7 coding sequence. RNA-seq analysis demonstrated that the c.842 + 15 T > C variant resulted in a leaky mRNA splicing event generating a premature stop codon right after the splicing donor site of exon 8. Moreover, the expression of ZNT7 protein was remarkably reduced by 80-96% in the affected brothers compared to the control cells. These findings strongly suggest that biallelic variants in SLC30A7 should be considered as a cause of growth retardation, testicular hypoplasia, and syndromic bone marrow failure.




IL-26 inhibits hepatitis C virus replication in hepatocytes

December 2021

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57 Reads

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10 Citations

Journal of Hepatology

Background & Aims Interleukin-26 (IL-26) is a proinflammatory cytokine involved in the pathophysiology of chronic inflammatory disorders. It has properties atypical for a cytokine, such as direct antibacterial activity and DNA-binding capacity. In a previous study, we observed an accumulation of IL-26 in fibrotic and inflammatory lesions in the livers of patients with chronic hepatitis C virus (HCV) infection and showed that infiltrating CD3⁺ lymphocytes were the principal source of IL-26. Surprisingly, immunohistochemical staining for IL-26 was also detected in the cytoplasm of hepatocytes from HCV-infected patients, even though these cells do not produce IL-26, even when infected with HCV. Based on this observation and possible interactions between IL-26 and nucleic acids, we investigated the possibility that IL-26 controlled HCV infection independently of the immune system. Methods We evaluated the ability of IL-26 to interfere with HCV replication in hepatocytes, and investigated the mechanisms by which IL-26 exerts its antiviral activity. Results We showed that IL-26 penetrated HCV-infected hepatocytes, where it interacted directly with HCV double-stranded RNA replication intermediates, thereby inhibiting viral replication. IL-26 interfered with viral RNA-dependent RNA polymerase activity, preventing the de novo synthesis of viral genomic single-stranded RNA. Conclusions These findings reveal a new role for IL-26 in direct protection against HCV infection, independently of the immune system, and increase our understanding of the antiviral defense mechanisms controlling HCV infection. Future studies should evaluate the possible use of IL-26 for treating other chronic disorders caused by RNA viruses, for which few treatments are currently available, or emerging RNA viruses. Lay summary This study sheds new light on the body’s arsenal for controlling HCV infection and identifies IL-26 as an antiviral molecule capable of blocking HCV replication. IL-26, which has unique biochemical and structural characteristics, penetrates infected hepatocytes and interacts directly with viral RNA, thereby blocking viral replication. IL-26 is, therefore, a new player in antiviral defenses, operating independently of the immune system. It is of considerable potential interest for treating HCV infection and other chronic disorders caused by RNA viruses for which few treatments are currently available, and for combating emerging RNA viruses.




PrimeFlow assay for EBER allows specific detection of EBV-containing cell lines and circulating EBV-infected B cells during severe IM. (A) FACS dot plots of EBER (left panels), Bacillus (middle panels), and RPL13A (right panels) stains using the PrimeFlow RNA assay of EBV⁻ cell lines (Jurkat, Ramos, and HEK) and EBV⁺ cell lines (HEK EBV-GFP, SNK-6, Raji, and LCL). The Bacillus probe targets a bacterial RNA, whereas the RPL13A probe targets a ubiquitously expressed ribosomal RNA, and they are used as negative and positive controls, respectively. The RPL13A probe is coupled to the fluorochrome Alexa Fluor 488, except for the analysis of HEK GFP-EBV, for which it is coupled to Alexa Fluor 647. (B) Upper panels show FACS dot plots of costaining with RPL13A and EBER probes (coupled to Alexa Fluor 488 and 647, respectively) of LCL cells treated for 72 h with TPA + ionomycin stimulation to induce the lytic cycle. LCL-1 and LCL-2 lines were obtained by infection with the BZLF1-KO BRLF1-KO B95-8 EBV strain and devoid of the essential BLZF1 and BRLF1 proteins required to induce the EBV lytic cycle. LCL cells were obtained by infection with the B95-8 EBV WT strain (WT B95-8 EBV). Lower panels show expression of BZLF1 (453 pb) and GAPDH (258 pb) fragment transcripts by RT-PCR in TPA + ionomycin–treated LCL-1, LCL-2, and LCL cell lines. GAPDH was used as an amplification control and DNA ladder (pb) on the left. (C) FACS dot plots of EBER expression by the PrimeFlow assay coupled with anti-CD3, anti-CD19, anti-CD16, or anti-CD56 staining of PBMCs from patients with IM. Dot plots are gated on eFluor⁻ CD14⁻ cells. The red gates in the dot plots highlight the EBV-infected cell subsets. Patients (Pt) 1.1, 1.2, and 1.3 had mild IM symptoms and low plasma EBV loads. Pt 1.4 and Pt 1.5 had severe IM symptoms and high plasma EBV loads. (D) Tonsil biopsy section from Pt 1.4 that has been costained with an EBER probe and anti-CD3 or anti-CD79a antibodies, showing infiltration of EBV-infected B cells in tissues. Magnification, ×400. Scale bars, 40 µm.
Detection by PrimeFlow EBER of peripheral EBV-infected B cells in PBMCs from patients with B-LPDs. (A and B) FACS dot plots of EBER expression by PrimeFlow assay coupled with anti-CD3, anti-CD19, anti-CD16, or anti-CD56 staining of PBMCs from patients affected with (A) Hodgkin lymphoma (Pt 2.1, Pt 2.2, and Pt 2.3) and post–liver transplantation B-LPD (Pt 2.4) or (B) B-LPD resulting from primary immune deficiencies, including CD70 (Pt 2.5), ZAP-70 (Pt 2.6), CTPS1 (Pt 2.7), and MAGT1 (Pt 2.8) deficiencies and XLP-1 (Pt 2.9, Pt 2.10). Dot plots are gated on eFluor⁻CD14⁻ cells. The red gates in the dot plots highlight the EBV-infected cell subsets. (C) Liver biopsy section from Pt 2.10 (XLP-1) that has been costained with an EBER probe and anti-CD79 antibody, showing infiltration of EBV-infected B cells. Magnification, ×400. Scale bar, 40 µm. Pt 2.10 analysis was repeated over time at different dates showing the same EBV-infected subset.
PrimeFlow EBER detection of peripheral EBV-infected T and NK cells in patients with post-transplant EBV⁺ T/NK cell lymphoproliferation and ENKTL. (A) FACS dot plots of EBER expression by PrimeFlow assay coupled with anti-CD3, anti-CD8, anti-CD16, anti-CD56, and anti-CD19 staining in PBMCs of patients with EBV⁺ T/NK cell lymphoproliferation after hematopoietic stem cell (Pt 3.1), cardiac (Pt 3.2), and liver transplant (Pt 3.3). A red square highlights the infected subset. Dot plots are gated on eFluor⁻CD14⁻ cells. (B) Gut biopsy sections from Pt 3.3 stained with anti-CD3 or EBER probe showing infiltration of EBV-infected T cells. Magnification, ×200. Scale bars, 40 µm. (C) FACS dot plots of EBER expression using the PrimeFlow assay coupled with anti-CD3, anti-CD19, anti-CD4, anti-CD5, anti-CD56, anti-CD16, and anti-CD2 staining of PBMCs from patients with ENKTL. PBMCs used in panels 1 and 2 are from different time points, explaining the slight differences in proportions of EBER⁺ cells. Dot plots are gated on eFluor⁻CD14⁻ cells. The red gates in the dot plots highlight the EBV-infected cell subsets. Pt 3.3, Pt 3.5, Pt 3.6, and Pt 3.7 analyses were repeated over time at different dates, showing the same EBV-infected subsets.
PrimeFlow EBER assay detects EBV-infected CD8⁺ T cells among PBMCs from patients with systemic EBV⁺ T cell lymphoma and EBV-associated HLH. (A) FACS dot plots of EBER expression by PrimeFlow assay coupled with anti-CD3, anti-CD4, anti-CD8, anti-CD16, anti-CD56, and anti-CD19 of PBMCs from patients with systemic EBV⁺ T cell lymphoma of childhood and EBV-associated HLH. Dot plots are gated on eFluor⁻CD14⁻ cells. The red gates in the dot plots highlight the EBV-infected cell subsets. (B) Lymph node biopsy section from Pt 4.1 costained with anti-CD3 and EBER probe (magnification, ×400) or stained with anti-CD8 (magnification, ×400) or anti-CD79a (magnification, ×50), showing infiltration by EBV-infected T cells. Liver biopsy section from Pt 4.2 costained with anti-CD8 and EBER probe showing infiltration of EBV-infected T cells (magnification, ×400). Scale bars, 40 µm, except for anti-CD79a, 200 µm.
Patients with hydroa vacciniforme–like LPD showed circulating EBV-infected γδ2 T cells by PrimeFlow EBER assay. FACS dot plots of EBER expression by PrimeFlow assay coupled with anti-CD19, anti-CD3, anti-CD4, anti-CD8, anti-TCR δ2, anti-CD16, and anti-CD56 of PBMCs from Pt 5.1, Pt 5.2, and Pt 5.3 with hydroa vacciniforme–like LPD. The red gates in the dot plots highlight the EBV-infected cell subsets. All dot plots were gated on eFluor⁻CD14⁻ cells. Fraction of positive cells in the fifth column (/CD3⁺) is calculated as the percentage of total CD3⁺ T cells. Pt 5.1 analysis was repeated over time at different dates showing the same EBV-infected subset.

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Rapid identification and characterization of infected cells in blood during chronic active Epstein-Barr virus infection
  • Article
  • Full-text available

August 2020

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671 Reads

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52 Citations

Epstein-Barr virus (EBV) preferentially infects epithelial cells and B lymphocytes and sometimes T and NK lymphocytes. Persistence of EBV-infected cells results in severe lymphoproliferative disorders (LPDs). Diagnosis of EBV-driven T or NK cell LPD and chronic active EBV diseases (CAEBV) is difficult, often requiring biopsies. Herein, we report a flow-FISH cytometry assay that detects cells expressing EBV-encoded small RNAs (EBERs), allowing rapid identification of EBV-infected cells among PBMCs. EBV-infected B, T, and/or NK cells were detectable in various LPD conditions. Diagnosis of CAEBV in 22 patients of Caucasian and African origins was established. All exhibited circulating EBV-infected T and/or NK cells, highlighting that CAEBV is not restricted to native American and Asian populations. Proportions of EBV-infected cells correlated with blood EBV loads. We showed that EBV-infected T cells had an effector memory activated phenotype, whereas EBV-infected B cells expressed plasma cell differentiation markers. Thus, this method achieves accurate and unambiguous diagnoses of different forms of EBV-driven LPD and represents a powerful tool to study their pathophysiological mechanisms.

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Citations (16)


... XMEN disease is considered an inborn error of immunity (IEI) classified within the subgroup of immune dysregulation with EBV susceptibility and lymphoproliferative conditions (2). Some new evidence in glycosylation defects (3) suggests "N-linked glycosylation defect" should be added to the XMEN acronym (4). ...

Reference:

Effects of two different variants in the MAGT1 gene on B cell subsets, platelet function, and cell glycome composition
MAGT1 deficiency in XMEN disease is associated with severe platelet dysfunction and impaired platelet glycoprotein N-glycosylation
  • Citing Article
  • May 2023

Journal of Thrombosis and Haemostasis

... Notably, the SLC30A7 gene is instrumental in the translocation of minerals within the organism, with a specific emphasis on Zinc. This mineral is indispensable for a plethora of enzymes that orchestrate growth, reproduction, developmental processes, and immune responses 42 . Consequently, maintaining cellular zinc equilibrium is paramount; a deficiency can culminate in hindered growth, compromised immunity, and reproductive challenges. ...

Identification of novel compound heterozygous variants in the SLC30A7 (ZNT7) gene in two French brothers with stunted growth, testicular hypoplasia, and bone marrow failure
  • Citing Article
  • February 2023

Human Molecular Genetics

... Still, in many cases, such as patients with common variable immunodeficiencies, noninfectious manifestations are present, and there is a need for additional and targeted therapies to prevent irreversible organ damage. 92 A recent study evaluated treatment with off-label Janus activating kinase inhibitors, predominantly ruxolitinib. 93 These were mostly prescribed in patients with a diagnosis of STAT1 or STAT3 GOF. ...

An appraisal of the frequency and severity of noninfectious manifestations in primary immunodeficiencies: A study of a national retrospective cohort of 1375 patients over 10 years
  • Citing Article
  • June 2022

... Viral infection alters the host cell environment, creating conditions conducive to viral replication and persistence [5]. DNA virus infections, in particular, have been associated with the development of chronic lesions [6]. ...

IL-26 inhibits hepatitis C virus replication in hepatocytes
  • Citing Article
  • December 2021

Journal of Hepatology

... При этом методом иммуногистохимии выявлена интенсивная экспрессия M-CSF гепатоцитами вокруг очагов поражений печени. Кроме того, инфекция ВГС и воспалительные цитокины усиливают выработку гепатоцитами in vitro M-CSF [44]. Таким образом, повышенный уровень M-CSF в плазме крови больных ХВГС может являться неблагоприяным фактором прогрессирования фиброза печени. ...

IL-34 and macrophage colony-stimulating factor are overexpressed in hepatitis C virus fibrosis and induce profibrotic macrophages that promote collagen synthesis by hepatic stellate cells
  • Citing Article
  • January 2014

... EBER flow FISH, using EBV-encoded small RNAs (EBERs), is an emerging tool that identifies infected cells in both their lytic and latent stages. Unlike PCR, it can differentiate EBV infections across various cell types, offering insights into the pathogenesis and disease mechanisms of EBV (Table 1) [20][21][22][23][24][25]. PTLD accounts for approximately 70% of all malignancies diagnosed following SOT in pediatric patients and occurs in up to 20% of cases, with mortality rates reaching 50% depending on the transplanted organ [12,13,26,27]. ...

Rapid identification and characterization of infected cells in blood during chronic active Epstein-Barr virus infection

... The management of secondary ITP in the context of PIDs mirrors that of primary ITP, involving corticosteroids as first-line treatment. However, second-line therapeutic strategy lacks robust evidence and draws upon limited published data 15 . Although retrospective studies have explored the use of rituximab 16 and splenectomy 17 in patients with ITP and PIDs, the use of TPO-RAs has only been documented in one case report and an observational study on eltrombopag in secondary ITP including data from 12 patients diagnosed with CVID 18,19 . ...

Traitement du PTI et de l’AHAI au cours du DICV : revue systématique de la littérature
  • Citing Article
  • May 2019

La Revue de Médecine Interne

... Some factors may negatively affect the immunization and the child will risk an infection despite the vaccine administration. Among these factors, in literature we have: a hepatitis B infection in the mother [7], the poor nutritional status [8], an HIV infection of the child [9], the low number of doses [10], the poor type of vaccine [11], and the male sex of the child [3]. In SSA, problems associated with conservation and cold chain of these vaccines could also affect their efficiency [3]. ...

Vaccins, adjuvants et réponse immunitaire post-vaccinale : bases immunologiques
  • Citing Article
  • May 2019

Revue Francophone des Laboratoires

... T cell responses can also be modulated by TLR-9 [32,33], which would explain the IL-26 overexpression in activated or transformed T cells [34]. Infiltrating CD3+ T lymphocytes were present next to B. burgdorferi biofilms, along with B. burgdorferi DNA, in post-mortem tissues from a patient with chronic illness [7]. ...

IL-26, a Cytokine With Roles in Extracellular DNA-Induced Inflammation and Microbial Defense

... Although HSCT has shown good results in this patient, performing HSCT to treat these sufferers should be taken with caution. Given RIPK1 plays a critical role in controlling cell death of the intestinal epithelium, HSCT might dampen intestinal in ammation but not rescue intrinsic intestinal phenotypes, similar to NF-kappa-B essential modulator de ciency, in which HSCT eliminates the increased susceptibility to recurrent/atypical infections, but does not cure the IBD phenotype 27 . ...

Hematopoietic stem cell transplantation in 29 patients hemizygous for hypomorphic IKBKG / NEMO mutations

Blood