Incidence et caractéristiques des hémopathies malignes au cours de l’artérite à cellules géantes

2021

Introduction L’arterite a cellules geantes (ACG) est une vascularite du sujet âge au cours de laquelle les cellules mononucleees jouent un role physiopathologique majeur. L’hematopoiese clonale est un phenomene dont la frequence augmente egalement avec l’âge et qui conduit a l’apparition de mutations responsables de la survenue d’hemopathies malignes (HM) ou de mutations des cellules effectrices de l’immunite responsables de pathologies inflammatoires. Notre hypothese est qu’il existe une association specifique entre certaines HM et l’ACG. Nous avons pu etudier cette hypothese en croisant les donnees du registre des hemopathies de Cote d’Or (RHEMCO) et celles de tous les laboratoires d’anat…

Liver X Receptor–Mediated Induction of Cholesteryl Ester Transfer Protein Expression Is Selectively Impaired in Inflammatory Macrophages

2009

Objective— Cholesteryl ester transfer protein (CETP) is a target gene for the liver X receptor (LXR). The aim of this study was to further explore this regulation in the monocyte-macrophage lineage and its modulation by lipid loading and inflammation, which are key steps in the process of atherogenesis. Methods and Results— Exposure of bone marrow–derived macrophages from human CETP transgenic mice to the T0901317 LXR agonist increased CETP, PLTP, and ABCA1 mRNA levels. T0901317 also markedly increased CETP mRNA levels and CETP production in human differentiated macrophages, whereas it had no effect on CETP expression in human peripheral blood monocytes. In inflammatory mouse and human mac…

Le tocilizumab corrige le déséquilibre de la balance Th17/Treg chez les patients atteints de polyarthrite rhumatoïde

2011

Brief Report: Inhibition of interleukin-6 function corrects Th17/Treg cell imbalance in patients with rheumatoid arthritis

2012

OBJECTIVE: From an immunologic standpoint, the mechanisms by which treatment with tocilizumab (TCZ), a humanized anti-interleukin-6 (anti-IL-6) receptor antibody, results in improvement in rheumatoid arthritis (RA) patients are still not fully understood. In vitro studies and studies in mouse models have demonstrated the critical role of IL-6 in Th17 cell differentiation. Th17 lymphocytes have been shown to be strongly involved in RA pathogenesis, and the purpose of this study was to investigate the effect of IL-6 blockade on the balance between Th17 cells and Treg cells in patients with active RA. METHODS: Patients with active RA for whom TCZ had been prescribed by a rheumatologist were en…

Should mild hypogammaglobulinemia be managed as severe hypogammaglobulinemia? A study of 389 patients with secondary hypogammaglobulinemia.

2014

Although secondary hypogammaglobulinemia is more frequent than primary hypogammaglobulinemia, its etiology and management are poorly described, particularly for mild hypogammaglobulinemia.This retrospective observational study included all adult patients with a gammaglobulin level6.4g/L on serum electrophoresis identified at Dijon teaching hospital between April and September 2012. Clinico-biological features, etiologies and infectious complications were collected at inclusion and compared between group 1 (gammaglobulin5g/L, severe hypogammaglobulinemia), and group 2 (gammaglobulin6.4 and ≥5g/L, mild hypogammaglobulinemia).Among the 4011 serum electrophoreses, 570 samples from 389 patients …

Modification de la réponse immunitaire au cours de la maladie de Rendu-Osler

2020

Introduction La maladie de Rendu-Osler (MRO) est une maladie genetique vasculaire rare caracterisee par une neo-angiogenese deregulee aboutissant a des epistaxis anemiantes parfois associees a malformations arterio-veineuses (MAV) pulmonaires, hepatiques ou cerebrales. La MRO est egalement associee a une lymphopenie T predominant sur les CD4+ dont les causes et les consequences sont mal connues. L’objectif de ce travail est de decrire les polarisations lymphocytaires Th1, Th2, Th17, Th1-17 et Treg au cours de la MRO. Patients et methodes Les patients atteints de MRO confirmee genetiquement ont ete prospectivement inclus lors de leur suivi habituel. Le score de severite des epistaxis (ESS), …

« Fausses et autres » artérites temporales

2021

Resume L’arterite a cellules geantes (ACG) est la plus frequente des vascularites affectant l’artere temporale (AT). Neanmoins, d’autres types de pathologies vasculaires, qu’il s’agisse de vascularite ou non, peuvent toucher l’AT. Parmi les vascularites, on peut citer les vascularites necrosantes, en particulier les vascularites associees aux anticorps anti-cytoplasme des polynucleaires neutrophiles (ANCA) qui peuvent affecter les petits vaisseaux peri-adventitiels de la paroi de l’AT et mimer certains symptomes de l’ACG, ces derniers n’etant generalement pas isoles, ce qui doit faire rechercher les ANCA. Certaines vascularites infectieuses peuvent egalement toucher l’AT comme l’infection p…

A New Prognosis Score to Predict Mortality After Acute Pneumonia in Very Elderly Patients

2016

International audience; Objectives: Acute pneumonia (AP) induces an excess of mortality among the elderly. We evaluated the value of a new predictive biomarker index compared to usual prognosis scores for predicting in-hospital and 1-year mortalities in elderly inpatients with AP.Design: Retrospective study in 6 clinical departments of a university hospital.Setting: Burgundy university hospital (France).Participants: All patients aged 75 and over with AP and hospitalized between January 1 and June 30, 2013, in the departments of medicine (5) and intensive care (1) of our university hospital.Measurements: A new index, which we named UBMo, was created by multiplying the uremia (U in the formu…

PIAS1 and STAT-3 impair the tumoricidal potential of IFN-γ-stimulated mouse dendritic cells generated with IL-15

2014

Primarily defined by their antigen-presenting property, dendritic cells (DCs) are being implemented as cancer vaccines in immunotherapeutic interventions. DCs can also function as direct tumor cell killers. How DC cytotoxic activity can be efficiently harnessed and the mechanisms controlling this nonconventional property are not fully understood. We report here that the tumoricidal potential of mouse DCs generated from myeloid precursors with GM-CSF and IL-15 (IL-15 DCs) can be triggered with the Toll-like receptor (TLR) 4 ligand lipopolysaccharide to a similar extent compared with that of their counterparts, conventionally generated with IL-4 (IL-4 DCs). The mechanism of tumor cell killing…

Haemolytic-uraemic syndrome during severe lupus nephritis: efficacy of plasma exchange

2012

Systemic lupus erythematosus (SLE) has been described as a cause of thrombotic microangiopathy, especially thrombotic thrombocytopenic purpura (TTP). Haemolytic-uraemic syndrome (HUS) is less frequent in SLE. We report a case of such an association during an episode of severe lupus nephritis in a young woman, who was successfully treated with steroids, cyclophosphamide and especially plasma exchange with plasma replacement. This report highlights the importance of recognising atypical HUS in SLE patients by looking for schistocytes in case of haemolytic anemia with a negative antiglobulin test, in order to begin plasma exchange.

Reducing the initial number of rituximab maintenance-therapy infusions for ANCA-associated vasculitides: randomized-trial post-hoc analysis

2020

AbstractObjectiveThe randomized, controlled MAINRITSAN2 trial was designed to compare the capacity of an individually tailored therapy [randomization day 0 (D0)], with reinfusion only when CD19+ lymphocytes or ANCA had reappeared, or if the latter’s titre rose markedly, with that of five fixed-schedule 500-mg rituximab infusions [D0 + D14, then months (M) 6, 12 and 18] to maintain ANCA-associated vasculitis (AAV) remissions. Relapse rates did not differ at M28. This ancillary study was undertaken to evaluate the effect of omitting the D14 rituximab infusion on AAV relapse rates at M12.MethodsMAINRITSAN2 trial data were subjected to post-hoc analyses of M3, M6, M9 and M12 relapse-free surviv…

Absence of Anti-Glomerular Basement Membrane Antibodies in 200 Patients With Systemic Lupus Erythematosus With or Without Lupus Nephritis: Results of…

2020

IntroductionAnti-glomerular basement membrane (GBM) antibodies are pathogenic antibodies first detected in renal-limited anti-GBM disease and in Goodpasture disease, the latter characterized by rapidly progressive crescentic glomerulonephritis combined with intra-alveolar hemorrhage. Studies have suggested that anti-GBM antibody positivity may be of interest in lupus nephritis (LN). Moreover, severe anti-GBM vasculitis cases in patients with systemic lupus erythematosus (SLE) have been described in the literature, but few studies have assessed the incidence of anti-GBM antibodies in SLE patients.ObjectiveThe main study objective was to determine if positive anti-GBM antibodies were present …

Antiplatelet Antibodies Do Not Predict the Response to Intravenous Immunoglobulins during Immune Thrombocytopenia

2020

Immune thrombocytopenia (ITP) is a rare autoimmune disease due to autoantibodies targeting platelet glycoproteins (GP). The mechanism of platelet destruction could differ depending on the specificity of antiplatelet antibodies: anti-GPIIb/IIIa antibodies lead to phagocytosis by splenic macrophages, in a Fc&gamma

Management of giant cell arteritis: Recommendations of the French Study Group for Large Vessel Vasculitis (GEFA).

2016

Abstract Purpose Management of giant cell arteritis (GCA, Horton's disease) involves many uncertainties. This work was undertaken to establish French recommendations for GCA management. Methods Recommendations were developed by a multidisciplinary panel of 33 physicians, members of the French Study Group for Large Vessel Vasculitis (Groupe d’etude francais des arterites des gros vaisseaux [GEFA]). The topics to be addressed, selected from proposals by group members, were assigned to subgroups to summarize the available literature and draft recommendations. Following an iterative consensus-seeking process that yielded consensus recommendations, the degree of agreement among panel members was…

ANCA-associated vasculitides: Recommendations of the French Vasculitis Study Group on the use of immunosuppressants and biotherapies for remission in…

2019

Treatment of vasculitides associated with anti-neutrophil cytoplasm antibodies (ANCA) (AAVs) has evolved dramatically in recent years, particularly since the demonstration of rituximab efficacy as remission induction and maintenance therapy for granulomatosis with polyangiitis and microscopic polyangiitis. In 2013, the French Vasculitis Study Group (FVSG) published recommendations for its use by clinicians. Since then, new data have made it possible to better specify and codify prescription of rituximab to treat AAVs. Herein, the FVSG Recommendations Committee, an expert panel comprised of physicians with extensive experience in the treatment and management of vasculitides, presents its con…

Infarctus du myocarde au cours de l’artérite à cellules géantes : étude de cohorte

2020

Introduction Le risque d’evenement cardiovasculaire est accru au cours de l’arterite a cellules geantes (ACG), en particulier dans les premiers mois suivant le diagnostic de la vascularite [1] . L’objectif de ce travail etait de decrire les caracteristiques des infarctus du myocarde (IDM) survenant chez des patients atteints d’ACG et de les comparer avec des IDM survenant chez des patients ne presentant pas d’ACG au moment de leur IDM. Patients et methodes Les patients atteints d’ACG ont ete identifies parmi la liste des biopsies d’artere temporale (BAT) qui montraient des lesions d’ACG et qui avaient ete analysees entre le 1er janvier 2001 et le 31 decembre 2016 dans les deux laboratoires …

L’augmentation de la réponse Th17 au cours de la maladie de Horton et de la PPR est liée à des modifications fonctionnelles et non quantitatives de l…

2011

Evans’ Syndrome: From Diagnosis to Treatment

2020

Evans’ syndrome (ES) is defined as the concomitant or sequential association of warm auto-immune haemolytic anaemia (AIHA) with immune thrombocytopenia (ITP), and less frequently autoimmune neutropenia. ES is a rare situation that represents up to 7% of AIHA and around 2% of ITP. When AIHA and ITP occurred concomitantly, the diagnosis procedure must rule out differential diagnoses such as thrombotic microangiopathies, anaemia due to bleedings complicating ITP, vitamin deficiencies, myelodysplastic syndromes, paroxysmal nocturnal haemoglobinuria, or specific conditions like HELLP when occurring during pregnancy. As for isolated auto-immune cytopenia (AIC), the determination of the primary or…

Altered distribution and function of splenic innate lymphoid cells in adult chronic immune thrombocytopenia

2018

IF 7.607; International audience; Innate lymphoid cells (ILCs) have been characterized as innate immune cells capable to modulate the immune response in the mucosae. Human ILCs have been rarely described in secondary lymphoid organs except in tonsils. Moreover, their function and phenotype in human secondary lymphoid organs during autoimmune diseases have never been studied. We took advantage of splenectomy as a treatment of immune thrombocytopenia (ITP) to describe and compare splenic ILC from 18 ITP patients to 11 controls. We first confirmed that ILC3 represented the most abundant ILC subset in human non-inflamed spleens, accounting for 90% of total ILC, and that they were mostly constit…

Caractérisation de l’anémie hémolytique auto-immune associée aux hémopathies lymphoïdes à partir du registre des hémopathies malignes de Côte d’Or

2020

Introduction L’anemie hemolytique auto-immune (AHAI) est une cytopenie auto-immune (CAI) caracterisee par une destruction des globules rouges par des auto-anticorps diriges contre certains de leurs antigenes de surface. Son incidence est estimee entre 1 et 3/100 000 personnes-annees (PA). Les AHAI a auto-anticorps chauds sont les plus frequentes et les formes secondaires, observees dans la moitie des cas, ont tendance a augmenter avec l’âge, notamment en association aux hemopathies malignes. Les donnees de la litterature reposent cependant sur de faibles cohortes ou des centres tertiaires, avec un possible biais de recrutement. L’objectif de notre etude est de decrire la frequence de l’AHAI…

Specific norovirus interaction with Lewis x and Lewis a on human intestinal inflammatory mucosa during refractory inflammatory bowel disease

2021

Inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), are progressive diseases affecting millions of people each year. Flare-ups during IBD result in severe mucosal alterations of the small intestine (in CD) and in the colon and rectum (in CD and UC).

Dendritic cells trigger tumor cell death by a nitric oxide-dependent mechanism.

2007

Abstract Dendritic cells (DCs) are well known for their capacity to induce adaptive antitumor immune response through Ag presentation and tumor-specific T cell activation. Recent findings reveal that besides this role, DCs may display additional antitumor effects. In this study, we provide evidence that LPS- or IFN-γ-activated rat bone marrow-derived dendritic cells (BMDCs) display killing properties against tumor cells. These cytotoxic BMDCs exhibit a mature DC phenotype, produce high amounts of IL-12, IL-6, and TNF-α, and retain their phagocytic properties. BMDC-mediated tumor cell killing requires cell-cell contact and depends on NO production, but not on perforin/granzyme or on death re…

Physiopathologie des vascularites primitives des gros vaisseaux

2016

Giant cell arteritis (GCA) and Takayasu's arteritis (TA) are two granulomatous vasculitis affecting large arteries that present specific epidemiological and clinical features. Their pathogenesis is not fully understood but major advances have been obtained during the last years, thus allowing the emergence of new therapeutic strategies. GCA and TA develop on a specific genetic background but share some similarities regarding the immunological pathways involved in their pathogenesis. The trigger of these diseases is not clearly identified but it is thought that an infectious agent could activate and lead to the maturation of dendritic cells that are localized in the adventitia of arteries. T…

Th1 and Th17 lymphocytes expressing CD161 are implicated in giant cell arteritis and polymyalgia rheumatica pathogenesis.

2012

International audience; OBJECTIVE: Giant cell arteritis (GCA) is the most frequently occurring vasculitis in elderly individuals, and its pathogenesis is not fully understood. The objective of this study was to decipher the role of the major CD4+ T cell subsets in GCA and its rheumatologic form, polymyalgia rheumatica (PMR). METHODS: A prospective study of the phenotype and the function of major CD4+ T cell subsets (Th1, Th17, and Treg cells) was performed in 34 untreated patients with GCA or PMR, in comparison with 31 healthy control subjects and with the 27 treated patients who remained after the 7 others withdrew. RESULTS: Compared with control subjects, patients with GCA and patients wi…

Stroke associated with giant cell arteritis: a population-based study

2014

Background Giant cell arteritis (GCA) is the most common vasculitis in people ≥50 years and can be associated with stroke. We aimed to evaluate the epidemiology and characteristics of stroke in patients with GCA. Methods All patients with a biopsy-proven diagnosis of GCA were identified among residents of the city of Dijon, France (152 000 inhabitants), between 2001 and 2012 using a prospective database. Among these, patients who suffered from stroke were retrieved by crossing data from the population-based Dijon Stroke Registry. Demographics and clinical features were recorded. We considered that the stroke was GCA-related if the stroke revealed GCA or occurred between the onset of symptom…

Tocilizumab en association à la prednisone au cours des 3 premiers mois de traitement de l’artérite à cellules géantes : résultats d’une étude prospe…

2016

Introduction L’arterite a cellules geantes (ACG) est une vascularite des gros vaisseaux habituellement traitee par corticoides. Ce traitement est remarquablement efficace mais doit etre donne a forte dose pendant 12 a 24 mois, ce qui est responsable d’une importante morbi-mortalite dans cette population âgee. Le tocilizumab (TCZ) est un anticorps monoclonal humanise dirige contre les recepteurs (soluble et membranaire) de l’interleukine-6 (IL-6). Son efficacite a recemment ete montree au cours du traitement de l’ACG [1] . Cependant, les donnees concernant l’evolution apres l’arret du TCZ manquaient dans cet essai therapeutique. De plus, la duree optimale de ce traitement couteux n’est pas c…

Immunologic effects of rituximab on the human spleen in immune thrombocytopenia

2011

Abstract Immune thrombocytopenia (ITP) is an autoimmune disease with a complex pathogenesis. As in many B cell–related autoimmune diseases, rituximab (RTX) has been shown to increase platelet counts in some ITP patients. From an immunologic standpoint, the mode of action of RTX and the reasons underlying its limited efficacy have yet to be elucidated. Because splenectomy is a cornerstone treatment of ITP, the immune effect of RTX on this major secondary lymphoid organ was investigated in 18 spleens removed from ITP patients who were treated or not with RTX. Spleens from ITP individuals had follicular hyperplasia consistent with secondary follicles. RTX therapy resulted in complete B-cell de…

Caractérisation de la thrombopénie immunologique associée aux hémopathies lymphoïdes à partir du registre des hémopathies malignes de Côte d’Or

2020

Introduction Le purpura thrombopenique immunologique (PTI) est une cytopenie auto-immune (CAI) caracterisee par une diminution de la duree de vie des plaquettes liee a la fois a leur destruction peripherique par les macrophages spleniques et a un defaut de production medullaire. Son incidence est estimee entre 3 et 4/100 000 personnes-annees (PA). S’il est le plus souvent primaire, il est associe dans 15–20 % des cas a d’autres maladies auto-immunes ou a des hemopathies malignes. Pour ces dernieres, les associations les plus frequentes sont rapportees avec la leucemie lymphoide chronique (LLC), la leucemie a grands lymphocytes T granuleux (LGL) et le lymphome de Hodgkin (LH) mais les donnee…

Impact du confinement dû au COVID-19 sur la prise en charge et le contrôle de l’artérite à cellules géantes

2020

Introduction L’arterite a cellules geantes (ACG) est une maladie multifactorielle dont la pathogenie n’est pas encore totalement comprise [1] . Malgre tout, il existe une relation dynamique entre predispositions genetiques et facteurs environnementaux via des modifications epigenetiques ayant un role dans le declenchement et l’evolution de cette pathologie [2] , [3] . Le confinement du a l’epidemie de COVID-19 a cree une situation sans precedent entrainant un stress physique et psychologique important chez de nombreuses personnes. Par ailleurs, la pression mediatique importante quant a l’usage des corticoides qui sont souvent prescrits chez les patients atteints d’ACG, etait tres anxiogene …

Pathogénie de l’artérite à cellules géantes

2012

Giant-cell arteritis (GCA) involves larges arteries, especially aorta and extra-cranial branches of external carotid. Histo-pathological lesions affect all the layers of the artery leading to a segmental and focal panarteritis with a polymorphic cell infiltrate including T cells, macrophages and multinucleated giant cells, a fragmented internal elastic lamina and an intimal hyperplasia. The pathophysiology of GCA is not fully understood. After dendritic cell activation in the adventitia, CD4T cells are recruited in the arterial wall and polarized into Th1 and Th17 cells that produce IFN-γ and IL-17. These cytokines activate macrophages, giant cells and smooth muscle cells inducing vascular …

Long-term efficacy of remission-maintenance regimens for ANCA-associated vasculitides.

2018

International audience; Objective - To compare long-term efficacy of remission-maintenance regimens in patients with newly diagnosed or relapsing antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitides. Methods - The 28-month Maintenance of Remission using Rituximab in Systemic ANCA-associated Vasculitis trial compared rituximab with azathioprine to maintain remission in patients with newly diagnosed or relapsing granulomatosis with polyangiitis, microscopic polyangiitis or renal-limited ANCA-associated vasculitis. Thereafter, prospective patient follow-up lasted until month 60. The primary endpoint was the major-relapse rate at month 60. Relapse and serious adverse event-free …

Inhibition of the HER2 pathway by n-3 polyunsaturated fatty acids prevents breast cancer in fat-1 transgenic mice

2013

Overexpression of the tyrosine kinase receptor, ErbB2/HER2/Neu, occurs in 25–30% of invasive breast cancer (BC) with poor patient prognosis. Due to confounding factors, inconsistencies still remain regarding the protective effects of n-3 polyunsaturated fatty acids (PUFAs) on BC. We therefore evaluated whether fat-1 transgenic mice, endogenously synthesizing n-3 PUFAs from n-6 PUFAs, were protected against BC development, and we then aimed to study in vivo a mechanism potentially involved in such protection. E0771 BC cells were implanted into fat-1 and wild-type (WT) mice. After tumorigenesis examination, we analyzed the expression of proteins involved in the HER2 signaling pathway and lipi…

FAS(CD95) ligand expression by tumor cell variants can be unrelated to their capacity to induce tolerance or immune rejection.

1999

According to the results of in vitro experiments, Fas(CD95) ligand expression by cancer cells might induce apoptosis of activated T cells and contribute to immune tolerance. However, Fas ligand expression had never been explored in vivo in tumor cell models yielding either immune response or tolerance. In the present study, we analyzed the expression and function of Fas ligand in 2 clones of tumor cells originating from the same rat colon carcinoma. REGb cells were immunogenic and yielded tumors that regressed in immune-competent syngeneic hosts, whereas PROb cells induced active tolerance and yielded progressive tumors. Fas ligand was expressed on the plasma membrane of both REGb and PROb …

Immune Thrombocytopenia: Recent Advances in Pathogenesis and Treatments

2021

Immune thrombocytopenia (ITP) is a rare autoimmune disease due to both a peripheral destruction of platelets and an inappropriate bone marrow production. Although the primary triggering factors of ITP remain unknown, a loss of immune tolerance—mostly represented by a regulatory T-cell defect—allows T follicular helper cells to stimulate autoreactive splenic B cells that differentiate into antiplatelet antibody-producing plasma cells. Glycoprotein IIb/IIIa is the main target of antiplatelet antibodies leading to platelet phagocytosis by splenic macrophages, through interactions with Fc gamma receptors (FcγRs) and complement receptors. This allows macrophages to activate autoreactive T cells …

Efficacy and safety of dapsone as second line therapy for adult immune thrombocytopenia: A retrospective study of 42 patients.

2017

Dapsone is recommended as a second line therapy in immune thrombocytopenia (ITP), but is underused because of its potential side effects. The medical charts of 42 ITP patients treated with dapsone (100 mg/day) were retrospectively reviewed in order to assess its efficacy and safety in daily clinical practice. The overall response rate was 54.8% (n = 22, with a complete response in 38.1%) with a median time to response of 29 days (24-41 days). Patients with complete response had shorter disease duration whereas no difference was observed between responders and non-responders regarding age, sex or previous treatments received. Importantly, after dapsone withdrawal, a sustained response was ob…

Is TNF-α really involved in giant cell arteritis pathogenesis?

2013

Giant cell arteritis (GCA) is the most frequent vasculitis in people >50 years, and glucocorticoids (GC) remain the cornerstone of the treatment. However, this long-term treatment is responsible for numerous GC-related complications.1 Thus, reliable GC-sparing drugs need to be explored. Seror et al 2 have recently reported the inefficacy of adalimumab, a humanised anti-TNF-α therapy, as a GC-sparing drug in the treatment of GCA. These clinical results contrast with previous studies reporting a production of TNF-α by giant cells and macrophages in GCA lesions.3 However, recent advance in the knowledge of GCA pathogenesis have shown that macrophages and giant cells are not involved in the fir…

Does Tocilizumab Indeed Reduce the Frequency of Th17 Cells? Comment on the Article by Thiolat et al

2014

Are IL-10+ regulatory Th17 cells implicated in the sustained response to glucocorticoid treatment in patients with giant cell arteritis? Comment on t…

2013

We have read with interest the recently published paper of Espigol-Frigole et al 1 in which the authors confirmed that interleukin (IL)-17 is highly expressed in giant cell arteritis (GCA) lesions.1–3 They also demonstrated for the first time that IL-17 expression in temporal artery biopsies (TABs) was correlated with a better outcome. Among other interesting results, the identification of Foxp3+IL-17+ T cells by confocal microscopy in TAB made the authors to hypothesize that these cells could be induced regulatory T cells (Treg) that may facilitate the remission of the disease under steroid therapy. …

Splenectomy for primary immune thrombocytopenia revisited in the era of thrombopoietin receptor agonists: New insights for an old treatment

2022

Although splenectomy is still considered the most effective curative treatment for immune thrombocytopenia (ITP), its use has significantly declined in the last decade, especially since the approval of thrombopoietin receptor agonists (TPO-RAs). The main objective of the study was to determine whether splenectomy was still as effective nowadays, particularly for patients with failure to respond to TPO-RAs. Our secondary objective was to assess, among patients who relapsed after splenectomy, the pattern of response to treatments used before splenectomy. This multicentre retrospective study involved adults who underwent splenectomy for ITP in France from 2011 to 2020. Response status was defi…

Allogeneic effector/memory Th-1 cells impair FoxP3+ regulatory T lymphocytes and synergize with chaperone-rich cell lysate vaccine to treat leukemia

2011

AbstractTherapeutic strategies combining the induction of effective antitumor immunity with the inhibition of the mechanisms of tumor-induced immunosuppression represent a key objective in cancer immunotherapy. Herein we demonstrate that effector/memory CD4+ T helper-1 (Th-1) lymphocytes, in addition to polarizing type-1 antitumor immune responses, impair tumor-induced CD4+CD25+FoxP3+ regulatory T lymphocyte (Treg) immunosuppressive function in vitro and in vivo. Th-1 cells also inhibit the generation of FoxP3+ Tregs from naive CD4+CD25−FoxP3− T cells by an interferon-γ–dependent mechanism. In addition, in an aggressive mouse leukemia model (12B1), Th-1 lymphocytes act synergistically with …

Emerging Therapies in Immune Thrombocytopenia

2021

Immune thrombocytopenia (ITP) is a rare autoimmune disorder caused by peripheral platelet destruction and inappropriate bone marrow production. The management of ITP is based on the utilization of steroids, intravenous immunoglobulins, rituximab, thrombopoietin receptor agonists (TPO-RAs), immunosuppressants and splenectomy. Recent advances in the understanding of its pathogenesis have opened new fields of therapeutic interventions. The phagocytosis of platelets by splenic macrophages could be inhibited by spleen tyrosine kinase (Syk) or Bruton tyrosine kinase (BTK) inhibitors. The clearance of antiplatelet antibodies could be accelerated by blocking the neonatal Fc receptor (FcRn), while n…

Flt3 ligand lessens the growth of tumors obtained after colon cancer cell injection in rats but does not restore tumor-suppressed dendritic cell func…

2000

A defective function of the antigen-presenting cells may represent one of the ways used by cancer cells to escape the immune response. We have previously shown that human and rat colon carcinomas were infiltrated by dendritic cells that did not express the B7 co-stimulatory molecules required for inducing an efficient T-cell response. Flt3 ligand is a cloned hematopoietic growth factor that markedly augments the number of functional dendritic and NK cells in lymphoid and non-lymphoid tissues and exerts anti-tumor activity in various experimental models. We show here that repeated Flt3 ligand administration delays the s.c. growth of rat colon cancer cells in syngeneic animals without inducin…

Physiopathologie des artérites à cellules géantes

2017

Resume L’arterite a cellules geantes (ACG) et l’arterite de Takayasu sont deux vascularites granulomateuses affectant les vaisseaux de gros calibre dont la cause exacte n’est pas connue. Neanmoins, les mecanismes physiopathologiques impliques au cours de l’ACG sont de mieux en mieux identifies et ont permis l’emergence de nouvelles cibles therapeutiques comme le blocage de la signalisation de l’interleukine-6 (IL-6). Le facteur declenchant de ces vascularites n’est pas connu mais l’hypothese, jamais confirmee a ce jour, d’un agent infectieux activant les cellules dendritiques de l’adventice est privilegiee. Cette activation de la reponse immunitaire innee permet le recrutement et l’activati…

Preferential splenic CD8+ T-cell activation in rituximab-nonresponder patients with immune thrombocytopenia

2013

The pathogenic role of B cells in immune thrombocytopenia (ITP) has justified the therapeutic use of anti-CD20 antibodies such as rituximab (RTX). However, 60% of ITP patients do not respond to RTX. To decipher the mechanisms implicated in the failure of RTX, and because the spleen plays a well-recognized role in ITP pathogenesis, 12 spleens from ITP patients who had been nonresponders to RTX therapy were compared with 11 spleens from RTX-untreated ITP patients and 9 controls. We here demonstrate that in RTX-nonresponder ITP patients, preferential Th1 and Tc1 T lymphocyte polarizations occur, associated with an increase in splenic effector memory CD8(+) T-cell frequency. Moreover, in the RT…

Dendritic cell-tumor cell hybrids and immunotherapy: what's next?

2011

Dendritic cells (DC) are professional antigen-presenting cells currently being used as a cellular adjuvant in cancer immunotherapy strategies. Unfortunately, DC-based vaccines have not demonstrated spectacular clinical results. DC loading with tumor antigens and DC differentiation and activation still require optimization. An alternative technique for providing antigens to DC consists of the direct fusion of dendritic cells with tumor cells. These resulting hybrid cells may express both major histocompatibility complex (MHC) class I and II molecules associated with tumor antigens and the appropriate co-stimulatory molecules required for T-cell activation. Initially tested in animal models, …

Le premier e-congrès de la SNFMI, Dijon 2020 : impressions, ressentis et bilans

2021

Interstitial Lung Disease during ANCA-Associated Vasculitis: A Poor-Prognosis Factor

2018

IF 7.873; International audience

Moving from Dermatomyositis Associated with Anti-Melanoma Differentiation-Associated Gene 5 Antibody to Anti-Melanoma Differentiation-Associated Gene…

2018

International audience