Eric Toussirot - Academia.edu (original) (raw)

Papers by Eric Toussirot

Frontiers in immunology, 2018

The IL-23/T helper 17 (Th17) axis plays an important role in joint inflammation in ankylosing spo... more The IL-23/T helper 17 (Th17) axis plays an important role in joint inflammation in ankylosing spondylitis (AS). Conventional CD4 Th17 cells are a major source of IL-17A. IL-22 is another cytokine implicated in AS pathophysiology and is produced by Th17 and Th22 cells. In this study, we aimed to analyze conventional and non-conventional T cell subsets producing IL-17A and IL-22 in patients with AS. We thus evaluated the intracellular staining for IL-17A, IL-22, and IFN-γ in peripheral blood mononuclear cells of 36 patients with AS and 55 age- and sex-matched healthy controls (HC). Conventional CD4 and CD8 T cells, γδ T cells, and mucosal-associated invariant T (MAIT) cells were evaluated. In patients with AS, we found a decreased frequency and number of γδ T cells, of MAIT cells and of IFN-γ CD4 and CD8 T cells. Th17-related IL-17A/IFN-γ CD4 T cells were decreased in AS. The number of IL-22 MAIT cells was higher in AS compared with HC, as well as the number of IFN-γ/IL-17A MAIT cells...

Clinical and experimental rheumatology, Jan 8, 2015

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Frontiers in Immunology, 2014

Psoriasis (Pso) is a common chronic cutaneous inflammatory disease involving the skin that is ass... more Psoriasis (Pso) is a common chronic cutaneous inflammatory disease involving the skin that is associated with serious comorbidities. Comorbidities in Pso include psoriatic arthritis (PsA), reduced quality of life, malignancy, depression, but also a constellation of associated conditions that enhance the cardiovascular (CV) risk. Indeed, obesity is common in patients with Pso or PsA and is considered to be a risk factor for the onset of these diseases. Patients with Pso and PsA share common obesity-related complications such as metabolic syndrome (MetS), dyslipidemia, diabetes or insulin resistance, and CV diseases. Chronic inflammation in Pso and PsA partially explains the development of atherosclerosis and CV diseases. In parallel, body composition is disturbed in patients with Pso or PsA, as suggested by anthropometric measurements, while an excess of abdominal adiposity is observed in PsA, enhancing the risk of MetS and CV diseases. Adipokines may link the adipose tissue to the obesity-related complications of Pso and PsA. Indeed, altered circulating levels of the adipokines leptin, adiponectin, visfatine, and resistin have been found in patients with Pso or PsA. In addition, an excess of adipose tissue may compromise the therapeutic response to traditional drugs or biological agents in Pso and PsA. This paper reviews the comorbidities that contribute to enhanced CV risk, the body composition results, and the potential role of adipokines in systemic inflammation and energetic balance in Pso and PsA.

Revue du Rhumatisme, 2012

ABSTRACT Objectifs Rapporter l’expérience de l’utilisation du rituximab (RTX) dans la polyarthrit... more ABSTRACT Objectifs Rapporter l’expérience de l’utilisation du rituximab (RTX) dans la polyarthrite rhumatoïde (PR) chez des patients avec un antécédent de sepsis sévère ou d’infections bactériennes récurrentes. Patients et méthodes Étude rétrospective observationnelle réalisée sur cinq services de rhumatologie ayant l’expérience des biothérapies. Les critères d’inclusion correspondaient à des PR avec un antécédent de sepsis sévère ou d’infections récurrentes (nécessitant hospitalisation ou antibiothérapie par voie intraveineuse) et contre indiquant l’initiation ou la poursuite d’un agent anti-TNFα. Résultats Parmi 161 PR traitées par RTX sur ces cinq centres, 30 cas répondaient aux critères d’inclusion : 23 femmes, sept hommes, âge moyen de 58,4 ± 11,8 ans, durée d’évolution de 11,4 ± 13,9 ans, facteurs rhumatoïdes présents dans 22 cas, utilisation antérieure des anti-TNFα dans 21 cas (un anti-TNF : n = 15 ; deux anti-TNF : n = 5 ; trois anti-TNF : n = 1). L’antécédent infectieux correspondait à une septicémie (n = 2), bronchopneumopathie ou abcès pulmonaire (n = 12), sepsis sur prothèse (n = 3), arthrite septique (n = 3), endocardite (n = 1), pyélonéphrite (n = 2), ostéite (n = 4), infections cutanées variées (érysipèle, cellulite, abcès cutané) (n = 6). Ces infections sont survenues sous anti-TNFα dans 21 cas et sans anti-TNF pour les autres. Lors du traitement par RTX, tous les patients avaient une corticothérapie quotidienne à une dose moyenne de 12 ± 7,9 mg. Les patients ont reçu un cycle de RTX dans 13 cas, deux cycles dans sept cas et trois cycles ou plus dans dix cas. Le délai moyen entre l’épisode infectieux et la première perfusion de RTX était de 20,1 ± 18,7 mois. Avec un recul de 19,3 ± 7,4 mois depuis le premier RTX, six patients (20 %) ont présenté une nouvelle infection après avoir reçu le RTX. Le taux des immunoglobulines après les cycles de RTX étaient dans les valeurs normales. Conclusion Cette série de patients avec un antécédent d’infections bactériennes sévères ou récurrentes montre une tolérance au RTX satisfaisante dans 80 % des cas. En pratique courante, l’administration de RTX semble bien tolérée sur le plan de la récidive des complications infectieuses. Une analyse à plus long terme est cependant nécessaire.

Metabolism, 2007

Adipokines such as leptin and adiponectin are involved in the regulation of inflammation. Ghrelin... more Adipokines such as leptin and adiponectin are involved in the regulation of inflammation. Ghrelin, a gastric peptide playing a role in the appetite regulation, possesses anti-inflammatory properties. In this study, we evaluated the circulating levels of adipokines (leptin as potential proinflammatory and adiponectin as anti-inflammatory marker) and ghrelin and the fat mass in patients with ankylosing spondylitis (AS). Serum leptin, adiponectin, and ghrelin were evaluated in 53 AS patients with active disease (mean Bath Ankylosing Spondylitis Disease Activity Index N40) and 35 controls. Fat and lean masses were determined using dual-energy x-ray absorptiometry. Fat and lean masses did not differ between patients and controls. Ankylosing spondylitis patients had lower leptin levels compared with controls, even after adjustment for fat mass (AS vs controls: leptin, 7.6 ± 1.3 ng/mL vs 10.3 ± 1.5 ng/mL; leptin [in nanograms per milliliter]/fat mass [in kilograms], 0.28 ± 0.04 vs 0.44 ± 0.04; P = .006 and P = .0003, respectively). Serum adiponectin did not differ between patients and controls, whereas circulating ghrelin was higher in AS patients (1354.6 ± 70.5 pg/mL vs 1008.0 ± 82.5 pg/mL; P = .001). However, all these results were significant only for male patients. No correlation was found between leptin and adiponectin, and erythrocyte sedimentation rate, C-reactive protein levels, tumor necrosis factor α, or Bath Ankylosing Spondylitis Disease Activity Index. Ankylosing spondylitis patients had no changes in fat mass. Leptin production was reduced in contrast with normal levels of adiponectin. These adipokine results, together with high serum ghrelin levels, may influence the inflammatory response in AS.

Arthritis & Rheumatism, 2001

Recent Patents on Inflammation & Allergy Drug Discovery, 2007

TNFα plays a pivotal role not only in the inflammatory process but also in the normal response ag... more TNFα plays a pivotal role not only in the inflammatory process but also in the normal response against pathogens and therefore, interfering with this cytokine may increase the risk of infection. TNFα antagonists are commonly used in daily clinical practice for the treatment of inflammatory rheumatic diseases including rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis and juvenile idiopathic arthritis since the beginning of 2000. The spectrum of pathogens giving infectious disease in patients under anti-TNFα therapies ranges from common bacteria to more opportunistic organisms such as Mycobacterium tuberculosis. The infections which were described with TNFα inhibitors may have a benign course or may be a serious, life threatening disease, and may be localized or disseminated. These TNFα inhibitors related infections were described in the randomized clinical trials, and were then declared to post- marketing surveillance systems and special registries. Tuberculosis (TB) is the most frequent opportunistic infection which has been reported with TNFα antagonists and the highest risk appears to be associated with infliximab, and at a lesser extent with etanercept. Currently available data and recent patents on the risk of TB with adalimumab are not sufficient to conclude, but TB cases were also reported with this agent. The description of TB infections with TNFα inhibitors led to the establishment of new guidelines for screening patients at high risk of developing TB. These data highlight the importance of post-marketing surveillance and special registries for accurately evaluating the safety profile and particularly the infectious risk of this very effective class of drug in inflammatory rheumatic diseases.

Arthritis Research & Therapy, 2001

We discuss the presence of anti-keratin antibodies (AKA) of the IgG class in patients with define... more We discuss the presence of anti-keratin antibodies (AKA) of the IgG class in patients with defined juvenile idiopathic arthritis (JIA). An indirect immunofluorescence test and rat oesophagus substrate was used for the detection and quantification of AKA antibodies in patients´ sera. Overall 33/60 patients with JIA had sera positive for AKA (55 %, P = 0,0001) ranging from 1:10 to 1:160 dilutions. Following idiopathic arthritis of childhood classification criteria AKA occurred in 2/7 patients with systemic disease (28,6 %), in 13/30 patients with RF negative polyarthritis (43,3 %, P = 0,008) and in 15/18 RF positive polyarthritis (83,3 %, P = 0,000002). AKA were also found in a small cohort of patients with oligoarthritis (1/3) and psoriatic arthritis (2/2). AKA positivity occurred in 3/26 healthy controls at a 1:20 dilution. The presence of AKA was correlated as well as with the severity of the disease. Our study revealed that AKA was present overall in 18/29 patients (62%) with severe JIA and in 12/26 patients (46,2 %) with non-severe disease, however this did not reach statistical significance (P = 0,18). We also observed that AKA remained positive regardless of disease activity. AKA were detectable in 55,6 % patients with active JIA and in 48,6 % patients in the complete or near remission.

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La Revue de Médecine Interne, 2010

Communications orales / La Revue de médecine interne 31S (2010) S35-S83 férences entre les 2 grou... more Communications orales / La Revue de médecine interne 31S (2010) S35-S83 férences entre les 2 groupes persistaient pour ces deux paramètres. À J0, 106 patients du groupe A (58 %) étaient sous prednisone contre 238 du groupe B (69 % ; p = 0,02). L'adhésion à la prescription de Plaquenil évaluée par l'investigateur sur une échelle visuelle analogique (de 0 à 10) était significativement plus basse dans le groupe A (8,99 ± 1,3 vs 9,3 ± 1,03 ; p = 0,003). Bien que seuls les patients ayant un SLEDAI ≤ 12 aient été inclus, la maladie était significativement plus active dans le groupe A (SLEDAI moyen : 2,41 ± 2,5 vs 1,88 ± 2,34 ; p = 0,016). Cette différence restait significative même lorsque l'étude se limitait aux patients traités par corticoïdes (2,94 ± 2,62 vs 2,16 ± 2,54, p = 0,019). Le taux de plaquettes était significativement plus bas dans le groupe A (225 ± 75 vs 268 ± 71 ; p < 0,0001). Les taux de la fraction C3 du complément, des anticorps anti-ADN (Farr et Elisa) et des anticorps anti-nucléosomes n'étaient pas différents entre les 2 groupes. En analyse multivariée, les facteurs associés aux (HCQ) basses étaient un taux bas de plaquettes (p < 0,0001), une clairance de la créatinine élevée (p < 0,001), l'absence de traitement par corticoïdes (p = 0,003), une moins bonne adhésion au traitement évaluée par l'investigateur (p = 0,003), un IMC élevé (p = 0,007) et l'activité du LES (p = 0,024). Conclusion.-Cette analyse préliminaire confirme l'association des (HCQ) basses avec l'activité du LES. Nous mettons en évidence les paramètres associés aux (HCQ) basses, certains étant inattendus.

Revue du Rhumatisme, 2008

PLOS ONE, 2015

Sirtuin 1 (Sirt1) is a class III histone deacetylase (HDAC) that modulates gene expression and is... more Sirtuin 1 (Sirt1) is a class III histone deacetylase (HDAC) that modulates gene expression and is involved in the regulation of proinflammatory cytokines. Interleukin-23 (IL-23) is produced by activated macrophages and dendritic cells and could fuel the progression of rheumatoid arthritis (RA). The goal of our study was to evaluate serum IL-23 levels and both Sirt1 activity and expression in peripheral blood mononuclear cells (PBMCs) in patients with RA compared to healthy controls (HC) and to determine the relationship between Sirt1 activity/expression and IL-23 levels. We assessed apoptosis in PBMCs of RA patients and its association with Sirt1 expression and serum IL-23. Serum IL-23 levels were increased in RA patients in comparison with controls. We found a positive correlation between the levels of serum IL-23 and serum IL-6 in RA patients. Decreased cytoplasmic Sirt1 activity was observed in RA patients with severe disease compared to HC. The expression of Sirt1 protein was significantly decreased in PBMCs of RA patients compared to HC using western blotting. Serum IL-23 levels correlated positively with the cytoplasmic Sirt1 activity in RA patients. Apoptosis rate of PBMCs isolated from RA patients was increased compared to HC and correlated negatively with the expression of Sirt1 protein and serum IL-23 levels. Levels of serum IL-23 and Sirt1 activity and expression were disturbed in RA parallel to increased PBMC apoptosis. Our findings might provide the rationale for the development of new therapeutic approaches in RA.

Case Reports in Rheumatology, 2014

Interferon beta (IFN- β ) is the first line therapy of relapsing-remitting multiple sclerosis. IF... more Interferon beta (IFN- β ) is the first line therapy of relapsing-remitting multiple sclerosis. IFN- β is a cytokine that can contribute to the development of systemic autoimmune disease including psoriasis. The development or the exacerbation of psoriasis during IFN- β treatment has been previously observed. We report the occurrence of arthritis and dactylitis in a multiple sclerosis patient with preexisting psoriasis diagnosed as a psoriatic arthritis. The IL-23/Th17 pathway is involved in psoriasis and psoriatic arthritis and it has been suggested that IFN- β therapy in patients with Th17-mediated disease may be detrimental. Together with previous similar reports, our case suggests that IFN- β should certainly be used with caution in patients with concomitant systemic autoimmune disease with IL-23/Th17 involvement.

Revue du Rhumatisme, 2005

Le DRESS syndrome (Drug Rash with Eosinophilia and Systemic Symptoms) est une réaction allergique... more Le DRESS syndrome (Drug Rash with Eosinophilia and Systemic Symptoms) est une réaction allergique d'hypersensibilité induite par certains médicaments et pouvant mimer en de nombreux points un lymphome malin. Nous rapportons l'observation d'une patiente âgée de 63 ans, atteinte d'une polyarthrite rhumatoïde et traitée depuis deux mois par sulfasalazine. Elle est hospitalisée quelques jours après la survenue d'un épisode grippal et l'apparition d'un érythème prurigineux maculopapuleux débutant au visage, sur le tronc et la racine des membres, hyperthermie à 41°C, quelques adénopathies et une hépato-splénomégalie. Biologiquement, il existe une hyperéosinophilie franche (9300/mm 3 ), une hyperlymphocytose, des cellules hyperbasophiles et un syndrome inflammatoire sévère. Le diagnostic retenu est celui de DRESS syndrome. La sérologie virale à HHV-6 est positive par immunofluorescence indirecte, en faveur d'une infection récente. Pour plusieurs auteurs, ce virus est incriminé dans la genèse du DRESS syndrome que ce soit lors d'une primo-infection ou lors d'une réactivation. Le taux de mortalité du DRESS syndrome reste élevé (10 %). Ce diagnostic doit rester présent à l'esprit, la sulfasalazine ayant déjà été incriminée dans ce type de réaction au même titre que l'hydantoïne, la D-penicillamine, l'allopurinol, l'hydrochlorothiazide, voir même la ciclosporine. La sérologie HHV-6 doit être réalisée de principe dans ce type de situation même si nous n'avons pas encore beaucoup de recul quant à l'association au syndrome d'hypersensibilité médicamenteuse. © 2004 Elsevier SAS. Tous droits réservés.

Case Reports in Rheumatology, 2013

We report two cases of acute pancreatitis following the administration of pamidronate given as an... more We report two cases of acute pancreatitis following the administration of pamidronate given as an anti-inflammatory agent for spondyloarthritis with a recurrence in one patient when the drug was reintroduced. The upper gastrointestinal toxicity of aminobisphosphonates is well known and this drug class could be added to the list of medications that are associated with the development of pancreatitis.

Revue du Rhumatisme, 2007

La Revue de Médecine Interne, 2001

Rheumatology, 2001

Objectives. In this cross-sectional study, we evaluated bone density using both dual-energy X-ray... more Objectives. In this cross-sectional study, we evaluated bone density using both dual-energy X-ray absorptiometry (DEXA) and quantitative ultrasound (QUS) techniques and examined the changes in body composition in patients with ankylosing spondylitis (AS).