Francis Corazza - Academia.edu (original) (raw)

Papers by Francis Corazza

An 18-years old African girl, suffered for almost 4 years of polyarthralgia, joint contractures a... more An 18-years old African girl, suffered for almost 4 years of polyarthralgia, joint contractures and a hardcover appearance of the skin suggestive of scleroderma. The clinical picture and a high level of CPK suggested Poly-myositis (PM). Search for anti nuclear Antibody (ANA) showed speckled pattern at 1/2500 titre, and subscreening revealed isolated anti-Ku antibody. This was more often reported in association with PM- SSc overlap syndrome. Skin biopsy favored linear scleroderma. Interestingly, muscle biopsy showed features typical of dermatomyositis (DM). No endocrine disorder or underlying mitotic process was registered. Corticosteroid therapy was initiated followed by main-

Gender differences and inflammation: an in vitro model of blood cells stimulation in prepubescent... more Gender differences and inflammation: an in vitro model of blood cells stimulation in prepubescent children

Early evidence during the COVID-19 pandemic indicated high levels of IL-6 in patients with severe... more Early evidence during the COVID-19 pandemic indicated high levels of IL-6 in patients with severe COVID-19. This led to the off-label use of tocilizumab (TCZ) during the first wave of the pandemic.We aimed to monitor IL-6 and several inflammatory cytokines in critically ill COVID-19 patients receiving off-label TCZ. Fifteen critically ill SARS-CoV-2 PCR confirmed cases were enrolled and serum samples were collected during 8 days, before and following administration of a single dose of TCZ. In parallel, a control group consisting of 8 non-treated COVID-19 patients not receiving TCZ was established. Serum profile of 12 cytokines (IL-1β, -2, -4, -6, -8, -10, -12, -13, -17, -18, TNF-α and INF-γ) and of IL-6R were assessed in these two groups. Although the increased IL-6 concentrations after TCZ infusion were expected, we observed an unexpected increase in IL-1β, -2, -4, -10, -12p70, -18 and IL-6R levels in the treated patients with maximal values reached 2 to 4 days after TCZ. In contra...

PLOS ONE, 2021

Background Like other helminths, hookworms (HW) induce a regulatory immune response able to modul... more Background Like other helminths, hookworms (HW) induce a regulatory immune response able to modulate and dampen reactivity of the host to antigens. No data about the evolution of the immune response after treatment are available. We aim to phenotype the regulatory immune response during natural HW infection and its evolution after treatment. Methodology Twenty hookworm infected (HW+) and 14 non-infected subjects HW–from endemic area in the periphery of Ho Chi Minh City were included. Blood and feces samples were obtained before, 2 and 4 weeks after treatment with Albendazole 400mg. Additional samples were obtained at 3 and 12 months in the HW+ group. Hematological parameters, Treg (CD4+CD25hiFoxP3hi) and surface molecules (CD39, CD62L, ICOS, PD-1, CD45RA) were measured as well as inflammatory and lymphocytes differentiation cytokines such as IL-1β, IL-6, IFNγ, IL-4, IL-17, IL-10, IL-2 and TGFβ. Results HW+ subjects showed higher Treg, TregICOS+, Treg PD1-, TregCD62L+ and CD45RA+FoxP...

ABSTRACTThe multiplicity, heterogeneity and dynamic nature of HIV-1 latency mechanisms are reflec... more ABSTRACTThe multiplicity, heterogeneity and dynamic nature of HIV-1 latency mechanisms are reflected in the current lack of functional cure for HIV-1 and in the various reported ex vivo potencies of latency- reversing agents. Here, we investigated the molecular mechanisms underlying the potency of the DNA methylation inhibitor 5-aza-2’-deoxycytidine (5-AzadC) in HIV-1 latency reversal. Doing so, we uncovered specific demethylation CpG signatures induced by 5-AzadC in the HIV-1 promoter. By analyzing the binding modalities to these CpG, we revealed the recruitment of the epigenetic integrator UHRF1 to the HIV-1 promoter. We further demonstrated the role of UHRF1 in DNA methylation- mediated silencing of the latent HIV-1 promoter. As a proof-of-concept to this molecular characterization, we showed that pharmacological downregulation of UHRF1 in ex vivo HIV+ patient cell cultures resulted in potent reactivation of latent HIV-1. Together, we identify UHRF1 as a novel actor in HIV-1 gene...

International Journal of Infectious Diseases, 2021

Background: Susceptibility to Covid-19 has been found to be associated with the ABO blood group, ... more Background: Susceptibility to Covid-19 has been found to be associated with the ABO blood group, with O type individuals being at a lower risk. However, the underlying mechanism has not been elucidated. Here, we aimed to test the hypothesis that Covid-19 patients might have lower levels of ABO antibodies than non-infected individuals as they could offer some degree of protection. Methods: After showing that the viral spike protein harbors the ABO glycan epitopes when produced by cells expressing the relevant glycosyltransferases, like upper respiratory tract epithelial cells, we enrolled 290 patients with Covid-19 and 276 asymptomatic controls to compare their levels of natural ABO blood group antibodies. Results: We found significantly lower IgM anti-A + anti-B agglutination scores in blood group O patients (76.93 vs 88.29, P-value = 0.034) and lower levels of anti-B (24.93 vs 30.40, P-value = 0.028) and anti-A antibodies (28.56 vs 36.50, P-value = 0.048) in blood group A and blood group B patients, respectively, compared to controls. Conclusion: In this study, we showed that ABO antibody levels are significantly lower in Covid-19 patients compared to controls. These findings could indicate that patients with low levels of ABO antibodies are at higher risk of being infected.

JCR: Journal of Clinical Rheumatology, 2020

From the Departments of *Immunology and Allergology (CIA), †Dermatology, and ‡Rheumatology, Centr... more From the Departments of *Immunology and Allergology (CIA), †Dermatology, and ‡Rheumatology, Centre Hospitalier Universitaire Brugmann (CHU-B), and §Department of Immunology, Le Laboratoire Hospitalier Universitaire de Bruxelles–Universitair Laboratorium van Brussel, Université Libre de Bruxelles (ULB), Brussels, Belgium. Correspondence: Yora Mostmans, MD, Departments of Dermatology and Immunology and Allergology, Centre Hospitalier Universitaire Brugmann (CHU-B), Université Libre de Bruxelles (ULB), Place AVan Gehuchten 4, 1020 Laken, Belgium. E‐mail: Yora.Mostmans@chu-brugmann.be. The authors declare no conflict of interest. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved. ISSN: 1076-1608 DOI: 10.1097/RHU.0000000000001450 FIGURE. Discrepant imaging in an RA patient with long known RP. Nailfo C) showing giant capillaries (*) with capillary loss and nonspecific abnorm (triangle) of single capillaries (A–C). D, Radiographic imaging of the patie proximal interphalangeal and metacarpophalangeal (MCP) joints (espec of fourth and fifth right MCP, and Hitchhiker thumb deformity bilaterall patient's right hand. Color online-figure is available at http://www.jclinrh

Biomolecules, 2020

Oxygenation conditions are crucial for growth and tumor progression. Recent data suggests a decre... more Oxygenation conditions are crucial for growth and tumor progression. Recent data suggests a decrease in cancer cell proliferation occurring after exposure to normobaric hyperoxia. Those changes are associated with fractal dimension. The purpose of this research was to study the impact of hyperoxia on apoptosis and morphology of leukemia cell lines. Two hematopoietic lymphoid cancer cell lines (a T-lymphoblastoid line, JURKAT and a B lymphoid line, CCRF-SB) were tested under conditions of normobaric hyperoxia (FiO2 > 60%, ± 18h) and compared to a standard group (FiO2 = 21%). We tested for apoptosis using a caspase-3 assay. Cell morphology was evaluated by cytospin, microphotography after coloration, and analysis by a fractal dimension calculation software. Our results showed that exposure of cell cultures to transient normobaric hyperoxia induced apoptosis (elevated caspase-3) as well as significant and precocious modifications in cell complexity, as highlighted by increased fract...

PLOS ONE, 2020

Introduction Coronavirus disease 2019 (COVID-19) appeared in China in December 2019 and has sprea... more Introduction Coronavirus disease 2019 (COVID-19) appeared in China in December 2019 and has spread around the world. High Interleukin-6 (IL-6) levels in COVID-19 patients suggest that a cytokine storm may play a major role in the pathophysiology and are considered as a relevant parameter in predicting most severe course of disease. The aim of this study was to assess repeated IL-6 levels in critically ill COVID-19 patients admitted to our Intensive Care Unit (ICU) and to evaluate their relationship with patient’s severity and outcome. Methods We conducted a retrospective study on patients admitted to the ICU with a diagnosis of COVID-19 between March 10 (i.e. the date of the first admitted patients) and April 30, 2020. Demographic, clinical and laboratory data were collected at admission. On the day of IL-6 blood concentration measurement, we also collected results of D-Dimers, C-Reactive Protein, white blood cells and lymphocytes count, lactate dehydrogenase (LDH) and ferritin as w...

Revue Française d'Allergologie, 2020

Introduction Les lymphocytes T regulateurs (Treg) jouent un role important dans le controle de la... more Introduction Les lymphocytes T regulateurs (Treg) jouent un role important dans le controle de la reaction inflammatoire asthmatique. Le but du travail est de les caracteriser au cours de la reponse asthmatique allergique au Dermatophagoides pt. (Dpt). Methodes 20 sujets asthmatiques legers, allergiques au Dpt ont ete exposes a un extrait Dpt (46 ng/m3 Der p1, ALK-Abello®) et a un placebo (Pcb) dans une chambre d’exposition (Alyatec®). Les reponses immediate et retardee etaient mesurees. Un prelevement sanguin etait obtenu a T0 et 6 h apres expositions. Les Treg (CD4CD25FoxP3) et certaines molecules effectrices (ICOS, PD1, CCR4 et CD39) etaient mesures par cytometrie en flux (FACSAria®). Les donnees ont ete analysees par analyses de la variance a mesures repetees avec le logiciel libre R, version 3.6.2. Une correlation lineaire avec la PD20 metacholine a ete recherchee (coefficient de Bravais-Pearson). Resultats 13 sujets ont presente une reponse duale (D), 4 une reponse immediate isolee (A) et 3 n’ont pas eu d’asthme (N). L’analyse statistique a pu etre realisee sur 18 sujets (17 pour CCR4). Apres exposition au Dpt, il n’y avait pas de modification des Treg ni d’ICOS et PD1. Par contre, il y avait une augmentation des CD39+ ( % Treg, p Discussion L’exposition au Dpt entraine une augmentation des Treg CD39+ et CCR4+ a 6 h. L’augmentation des CD39+ est differente selon la reponse asthmatique suggerant un role de ces cellules dans son controle. Ceci est renforce par la relation entre les Treg CD39+ et l’hyperreactivite bronchique non specifique. Conclusion L’exposition aux Dpt dans l’asthme entraine une augmentation des Treg ayant des caracteristiques suppressives (CD39) ou impliques dans leur migration pulmonaire (CCR4) et limitant l’inflammation bronchique allergique.

Frontiers in Immunology, 2018

In humans, acid-base balance is crucial to cell homeostasis. Acidosis is observed in numerous inf... more In humans, acid-base balance is crucial to cell homeostasis. Acidosis is observed in numerous inflammatory processes, primarily acute conditions such as sepsis, trauma, or acute respiratory distress where females tend to exhibit better prognosis compared with males. The mechanisms underlying these gender-dependent differences are multiple, probably involving hormonal and genetic factors, particularly the X chromosome. Although pH influences multiple immunological functions, gender differences in acid-base balance have been poorly investigated. In this review, we provide an update on gender differences in human susceptibility to inflammatory diseases. We additionally discuss the potential impact of acid-base balance on the gender bias of the inflammatory response in view of our recent observation that girls present higher neutrophilic inflammation and lower pH with a trend toward better prognosis in severe sepsis. We also highlight the potent role played by endothelial cells in gender differences of inflammation through activation of proton-sensing G protein-coupled receptors.

Frontiers in Immunology, 2017

Revue Française d'Allergologie, 2016

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PLOS Pathogens, 2015

The persistence of latently infected cells in patients under combinatory antiretroviral therapy (... more The persistence of latently infected cells in patients under combinatory antiretroviral therapy (cART) is a major hurdle to HIV-1 eradication. Strategies to purge these reservoirs are needed and activation of viral gene expression in latently infected cells is one promising strategy. Bromodomain and Extraterminal (BET) bromodomain inhibitors (BETi) are compounds able to reactivate latent proviruses in a positive transcription elongation factor b (P-TEFb)-dependent manner. In this study, we tested the reactivation potential of protein kinase C (PKC) agonists (prostratin, bryostatin-1 and ingenol-B), which are known to activate NF-κB signaling pathway as well as P-TEFb, used alone or in combination with P-TEFb-releasing agents (HMBA and BETi (JQ1, I-BET, I-BET151)). Using in vitro HIV-1 post-integration latency model cell lines of T-lymphoid and myeloid lineages, we demonstrated that PKC agonists and P-TEFb-releasing agents alone acted as potent latencyreversing agents (LRAs) and that their combinations led to synergistic activation of HIV-1

Medical Hypotheses, 2011

The ''normobaric oxygen paradox'' is a dual mechanism by which oxygen regulates the expression of... more The ''normobaric oxygen paradox'' is a dual mechanism by which oxygen regulates the expression of the Hypoxia Inducible Factor 1 alpha (HIF-1a). The HIF-1a-depending gene regulation is responsible for many different genetic expressions including EPO and VEGF that are usually expressed in parallel. First, VEGF under-expression could decrease tumor angiogenesis leading to a decrease in tumor growth or even apoptosis of cancer cells. Second, induction of EPO-expression can provide cytoprotection. Altogether, this could be deleterious for cancer cells while helping non-malignant cells (at least neural and cardiac) cells to be protected from the side effects of chemotherapy. Eventually, HIF induction could boost immune response by inflammatory cells, increasing their antitumor activity.

Rapid progress has occurred recently in characterizing the molecular structure of the glycoprotei... more Rapid progress has occurred recently in characterizing the molecular structure of the glycoproteins controlling the growth, maturation and functional activities of hematopoietic cells. Several of these factors have been purified and cDNAs have been cloned, providing them in sufficient quantities for study and eventual clinical use. Both availability of these molecules and in vitro colony assays have revealed a large number of effects on erythroid differentiation. But, except erythropoietin (EPO), the physiological role of these hormones and their relative contributions to normal erythropoiesis remain to be specified. This paper attempts to review the most important data on this topic in 1990.

Blood

1630 Sickle cell disease (SCD) is considered as a hypercoagulable state through still a mechanism... more 1630 Sickle cell disease (SCD) is considered as a hypercoagulable state through still a mechanism poorly understood. Our hypothesis is that poor platelet plasma (PPP) from SCD children may contain a high phospholipids procoagulant activity. This study aimed 1° at using and comparing two different assays to detect the procoagulant activity of endogenous phospholipids (ePL) in the PPP of SCD children in steady state compared to normal controls, 2° at assessing the influence of the clinical state and treatment on this procoagulant activity. Patients: A group of 30 SCD children aged between 2 – 20 years (median=9, 16 males, 14 females) were studied: 12/30 didn't receive any specific treatment, 6/30 were chronically transfused (TRX) and 12/30 were treated by hydroxyurea (HU). 11/30 were previously admitted because of a vaso-occlusive crisis (VOC). 24 SCD patients were HbSS, 4 HbSC, and 2 HbSβ. Controls: 18 remaining samples from children aged between 3 – 20 years (median=9, 11 males,...