ORCID Profile
0000-0002-7020-1954
Current Organisation
Université de Genève
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Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-06-2020
DOI: 10.1212/WNL.0000000000009727
Abstract: The predominance of extramuscular manifestations (e.g., skin rash, arthralgia, interstitial lung disease [ILD]) as well as the low frequency of muscle signs in anti–melanoma differentiation-associated gene 5 antibody–positive (anti-MDA5+) dermatomyositis caused us to question the term myositis-specific antibody for the anti-MDA5 antibody, as well as the homogeneity of the disease. To characterize the anti-MDA5+ phenotype, an unsupervised analysis was performed on anti-MDA5+ patients (n = 83/121) and compared to a group of patients with myositis without anti-MDA5 antibody (anti-MDA5− n = 190/201) based on selected variables, collected retrospectively, without any missing data. Within anti-MDA5+ patients (n = 83), 3 subgroups were identified. One group (18.1%) corresponded to patients with a rapidly progressive ILD (93.3% p 0.0001 across all) and a very high mortality rate. The second subgroup (55.4%) corresponded to patients with pure dermato-rheumatologic symptoms (arthralgia 82.6% p 0.01) and a good prognosis. The third corresponded to patients, mainly male (72.7% p 0.0001), with severe skin vasculopathy, frequent signs of myositis (proximal weakness: 68.2% p 0.0001), and an intermediate prognosis. Raynaud phenomenon, arthralgia/arthritis, and sex permit the cluster appurtenance (83.3% correct estimation). Nevertheless, an unsupervised analysis confirmed that anti-MDA5 antibody delineates an independent group of patients (e.g., dermatomyositis skin rash, skin ulcers, calcinosis, mechanic's hands, ILD, arthralgia/arthritis, and high mortality rate) distinct from anti-MDA5− patients with myositis. Anti-MDA5+ patients have a systemic syndrome distinct from other patients with myositis. Three subgroups with different prognosis exist.
Publisher: Elsevier BV
Date: 03-2020
Publisher: Elsevier BV
Date: 11-2016
DOI: 10.1016/J.NMD.2016.07.006
Abstract: Pompe disease is an inherited lysosomal disease in which there is a decrease or absence of acid alpha-glucosidase activity. This enzyme defect induces glycogen storage in different tissues, especially muscle and heart, resulting in muscle weakness, respiratory failure and heart disease. Substitutive enzyme replacement therapy (ERT) dispensed every two weeks is the only treatment that has shown benefits. However, this treatment induces hypersensitivity for half of the treated patients. Reactions range from mild to severe, sometimes requiring ERT suspension and anti-anaphylaxis drug administration. Understandably, high amount of acid alpha-glucosidase infusion seems to be identified by the immune system as a danger associated molecular pattern, and induce an immune reaction, involving sometimes, but not always, immunoglobulin E (IgE) production and activating mast and basophil polynuclear cells. Considering the lack of therapeutic alternatives and the proved benefit of ERT, desensitization finds its place here. We hereby report the case of a patient for whom a simplified desensitization protocol ("SWORD": Start With One Regular Drop) was successfully achieved, allowing ERT to be pursued, resulting eventually in clinical improvement.
Publisher: EDP Sciences
Date: 11-2017
Publisher: Oxford University Press (OUP)
Date: 06-05-2020
DOI: 10.1093/CID/CIZ793
Publisher: Elsevier BV
Date: 02-2022
DOI: 10.1016/J.NMD.2021.10.003
Abstract: Eosinophilic myositis belong to the idiopathic inflammatory myopathies and are defined by an inflammatory infiltrate composed of eosinophils within the muscle. To date, no consensus exists for diagnosis and care of such patients. The aim of this review was to describe clinical and histological presentation, treatment, and outcome of eosinophilic myositis based on a systematic review of all published histologically proven cases of eosinophilic myositis. A total of 453 records were identified in MEDLINE until November 2020. A total of 69 published cases were identified. The analysis of these allowed the distinction of the 3 previously described pathological subtypes: focal eosinophilic myositis (n = 17) diffuse eosinophilic myositis (n = 36) and eosinophilic perimyositis (n = 16). We propose a simple algorithm for diagnosis and treatment strategy for the care of patient with muscular symptoms and blood eosinophilia. This work also highlights eosinophilic myositis pathogenesis and the need for careful investigations in order to rule out differential diagnoses.
Publisher: Elsevier BV
Date: 11-2020
Publisher: American Thoracic Society
Date: 15-01-2021
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 21-02-2018
DOI: 10.1212/WNL.0000000000005160
Abstract: To better define in a cohort study the clinical and pathologic features of focal myositis (FM). With the use of the usual clinicopathologic definition, each confirmed case of FM in the Lyon University Hospital's myopathologic database between 2000 and 2016 was retrieved. Clinical, pathologic, imaging, serologic, and therapeutic data were collected. When data were missing but feasible, appropriate pathologic analyses were performed. Of the 924 patients included in the database, 37 (4%) had confirmed FM (14 female, 23 male patients). The main symptoms were pain (n = 30, 81%), muscular mass (n = 16, 43%), erythema at the site of FM (n = 12, 32%), and fever (n = 9, 24%). Serum creatine kinase was normal in most patients (81%) serum immune abnormalities were frequent (inflammatory syndrome in sera [39%], dysglobulinemia [52%], and anti-nuclear antibody positivity [29%]). In addition to confirming previously reported findings, pathologic analyses found significant rates of vasculitis (68%) and fasciitis (73%). Here, FM appeared frequently to be associated with other diseases such as immune-mediated inflammatory disease (IMID 32%), neoplasia (24%), and radiculopathy (11%). Regarding outcomes, 64% of the cases had received immunosuppressive drugs, and the relapse rate was 41%. The present study suggests that FM is not as innocuous as previously believed, particularly considering the associated disorders. Notably, patients with FM should receive careful IMID and neoplasia screening.
Publisher: Elsevier BV
Date: 04-2021
Publisher: BMJ
Date: 11-04-2019
Publisher: Springer New York
Date: 10-12-2016
DOI: 10.1007/978-1-4939-6728-5_11
Abstract: Extracellular vesicles (EVs) are composed of microvesicles and exosomes. Exosomes are small membrane vesicles (40-120 nm sized) of endosomal origin released in the extracellular medium from cells when multivesicular bodies fuse with the plasma membrane, whereas microvesicles (i.e., shedding vesicles, 100 nm to 1 μm sized) bud from the plasma membrane. Exosomes and microvesicles carry functional proteins and nucleic acids (especially mRNAs and microRNAs) that can be transferred to surrounding cells and tissues and can impact multiple dimensions of the cellular life. Most of the cells, if not all, from neuronal to immune cells, release exosomes and microvesicles in the extracellular medium, and all biological fluids including blood (serum lasma), urine, cerebrospinal fluid, and saliva contain EVs.Prion-infected cultured cells are known to secrete infectivity into their environment. We characterized this cell-free form of prions and showed that infectivity was associated with exosomes. Since exosomes are produced by a variety of cells, including cells that actively accumulate prions, they could be a vehicle for infectivity in body fluids and could participate to the dissemination of prions in the organism. In addition, such infectious exosomes also represent a natural, simple, biological material to get key information on the abnormal PrP forms associated with infectivity.In this chapter, we describe first a method that allows exosomes and microvesicles isolation from prion-infected cell cultures and in a second time the strategies to characterize the prions containing exosomes and their ability to disseminate the prion agent.
Publisher: Oxford University Press (OUP)
Date: 03-04-2023
DOI: 10.1093/RHEUMATOLOGY/KEAD154
Abstract: Among specific autoantibodies in DM, the anti–small ubiquitin-like modifier activating enzyme (SAE) antibody is rare. We aim to describe the clinical characteristics, cancer prevalence, and muscle pathology of anti-SAE–positive DM. Patients with a diagnosis of DM and sera positive for the anti-SAE antibody were recruited from 19 centres in this retrospective observational study. The available muscular biopsies were reviewed. We conducted a comparison with anti-SAE–negative DM and a review of the literature. Of the patients in the study (n = 49), 84% were women. Skin involvement was typical in 96% of patients, with 10% having calcinosis, 18% ulceration and 12% necrosis 35% presented with a widespread skin rash. Muscular disease affected 84% of patients, with mild weakness [Medical Research Council (MRC) scale 4 (3, 5)], although 39% of patients had dysphagia. Muscular biopsies showed typical DM lesions. Interstitial lung disease was found in 21% of patients, mainly with organizing pneumonia pattern, and 26% of patients showed dyspnoea. Cancer-associated myositis was diagnosed in 16% of patients and was responsible for the majority of deaths, its prevalence being five times that of the general population. IVIG therapy was administered to 51% of the patients during the course of the disease. Comparison with anti-SAE–negative DM (n = 85) showed less and milder muscle weakness (P = 0.02 and P = 0.006, respectively), lower creatinine kinase levels (P & 0.0001) and less dyspnoea (P = 0.003). Anti-SAE positive DM is a rare subgroup associated with typical skin features but a potentially diffuse rash, a mild myopathy. Interstitial lung disease defines an organizing pneumonia pattern. Cancer associated DM prevalence is five times that of the general population. ClinicalTrials.gov, clinicaltrials.gov, NCT04637672.
Publisher: Oxford University Press (OUP)
Date: 24-03-2018
Publisher: Wiley
Date: 31-03-2023
DOI: 10.1111/NAN.12900
Publisher: Wiley
Date: 08-07-2019
DOI: 10.1002/ART.40895
Abstract: Anti-transcription intermediary factor 1γ (anti-TIF1γ) antibodies are the main predictors of cancer in dermatomyositis (DM). Yet, a substantial proportion of anti-TIF1γ-positive DM patients do not develop cancer. This study was undertaken to identify biomarkers to better evaluate the risk of cancer and mortality in DM. This multicenter study was conducted in adult anti-TIF1γ-positive DM patients from August 2013 to August 2017. Anti-TIF1γ autoantibody levels and IgG subclasses were identified using a newly developed quantitative immunoassay. Age, sex, DM signs and activity, malignancy, and creatine kinase (CK) level were recorded. Risk factors were determined by univariate and multivariate analysis according to a Cox proportional hazards regression model. Among the 51 adult patients enrolled (mean ± SD age 61 ± 17 years ratio of men to women 0.65), 40 (78%) had cancer and 21 (41%) died, with a mean ± SD survival time of 10 ± 6 months. Detection of anti-TIF1γ IgG2 was significantly associated with mortality (P = 0.0011) and occurrence of cancer during follow-up (P 385. None of the patients developed cancer after 24 months of follow-up. Univariate survival analyses showed that mortality was also associated with age >60 years (P = 0.0003), active DM (P = 0.0042), cancer (P = 0.0031), male sex (P = 0.011), and CK level >1,084 units/liter (P = 0.005). Multivariate analysis revealed that age >60 years (P = 0.015) and the presence of anti-TIF1γ IgG2 (P = 0.048) were independently associated with mortality. Our findings indicate that anti-TIF1γ IgG2 is a potential new biomarker of cancer that should be helpful in identifying the risk of mortality in anti-TIF1γ-positive DM patients.
Publisher: Cold Spring Harbor Laboratory
Date: 13-11-2020
DOI: 10.1101/2020.11.10.20226886
Abstract: To assess the effectiveness of corticosteroids among elderly patients with COVID-19 pneumonia requiring oxygen. Comparative observational study based on routine care data. Baseline characteristics of patients were balanced using propensity-score inverse probability of treatment weighting. Geriatric and infectious diseases wards from 36 hospitals in France and Luxembourg. Adults 80 years old PCR confirmed SARS-CoV-2 infection or typical CT-scan images, requiring oxygen ≥ 3L/min and with an inflammatory syndrome (C-reactive protein ≥ 40mg/L). The primary outcome was overall survival at day 14. The secondary outcome was the proportion of patients discharged from hospital to home/rehabilitation on day 14. Adverse events were abstracted from electronic health records. Among the 267 patients included in the analysis, 96 were assigned to the treatment group. Median age was 86, interquartile range 83 to 90 and 95% had a SARS-CoV-2 PCR-confirmed diagnosis. Use of corticosteroids was significantly associated with an increased survival (weighted hazard ratio [wHR] 0.66, 95% CI 0.44 to 0.97). There was no significant difference between the treatment and control groups regarding the proportion of patients discharged to home/rehabilitation at day 14 (wRR 1.11, 95% CI 0.68 to 1.81). Twenty-two (16.7%) patients receiving corticosteroids developed adverse events while only 11 (6.4%) from the control group did. Corticosteroids were associated with a significant increase the day-14 overall survival of patients over 80 years old hospitalized for severe COVID-19. We certify that this work is novel. As of today, studies on the efficacy of corticosteroids did not specifically target elderly patients. Among older patients aged over 80 years old, the RECOVERY trial found no difference in the survival of patients treated or not with dexamethasone. However, the heterogeneity in the severity of infection within the latter subgroup limited the drawing of strong conclusions
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 24-05-2022
DOI: 10.1212/WNL.0000000000200271
Abstract: The idiopathic inflammatory myopathy dermatomyositis is an acquired disease that involves muscle, lung, and skin impairments. Patients with dermatomyositis show a wide range of severity of proximal skeletal muscle weakness, associated with inflammatory infiltrates, vasculitis, capillary dropout, and perifascicular myofiber atrophy. Muscles of patients with dermatomyositis show signs of muscle regeneration. Because muscle stem cells (MuSCs) are responsible for myofiber repair, we wondered whether the proliferative properties of MuSCs are altered in dermatomyositis muscle. We investigated the role of type I interferon (IFN-I) in this process because dermatomyositis is associated with sustained inflammation with high IFN-I levels. MuSCs isolated from normal muscles and those from adult and juvenile patients with dermatomyositis were grown in culture and analyzed in vitro for their proliferating properties, myogenic capacities, and senescence. Gain- and loss-of-function experiments were performed to assess the role of IFN-I signaling in the proliferative capacities of MuSCs. MuSCs derived from 8 adult patients with dermatomyositis (DM-MuSCs) (5 severe form and 3 mild form, established from histologic evaluation), from 3 patients with juvenile dermatomyositis, and from normal muscle were used to analyze their myogenesis in vitro. DM-MuSCs exhibited strongly reduced proliferating capacities as compared with healthy MuSCs (−31% to −43% for mild and severe dermatomyositis, respectively), leading to poor myotube formation (−36% to −71%). DM-MuSCs were enriched in senescent, β-galactosidase–positive cells, partly explaining the proliferation defect. Gain- and loss-of-function experiments were performed to assess the role of IFN-I on the proliferative capacity of MuSCs. High concentrations of IFN-I decreased the proliferation of healthy MuSCs. Similarly, conditioned medium from DM-MuSCs decreased the proliferation of healthy MuSCs (−15% to −22%), suggesting the delivery of an autocrine effector. Pharmacologic blockade of IFN signaling (using ruxolitinib or anti–IFN receptor antibodies) in DM-MuSCs rescued their proliferation up to the control values. These results show that autocrine IFN-I signaling prevents MuSC expansion, leading to muscle repair deficit. This process may explain the persistent muscle weakness observed in patients with severe dermatomyositis.
Publisher: Oxford University Press (OUP)
Date: 18-07-2023
DOI: 10.1093/RHEUMATOLOGY/KEAD347
Abstract: Inaugural axial muscle involvement, defined as dropped head syndrome (DHS) and/or c tocormia (CC), is poorly described in inflammatory myopathies (IM). This study aimed to further characterize IM patients with inaugural DHS/CC, their outcome and care management. This retrospective study included IM patients diagnosed between 2000 and 2021. The main inclusion criterion was IM revealed by axial muscle deficit (DHS/CC). Twenty-seven patients were included median (IQR) age at first symptoms was 66.0 years (55.5–75.0) 21 were female (77.8%). There were nine IBM, 33.3%, nine overlap myositis (OM, 33.3%), five DM, 18.5%, two immune checkpoint inhibitor-related myositis (7.4%), one focal myositis (3.7%) and one myositis with anti-Hu antibodies (3.7%). Age at first symptoms was ≤70 years in 16 patients (59.3%), including all DM patients and 8/9 OM patients (88.9%). In this group, partial remission of the disease was obtained in 9/16 (56.3%) and complete remission in 1/16 patients (6.3%) regression of DHS/CC was achieved in 3/16 patients (18.8%). Conversely, in the group of 11 patients aged & years at first symptoms, there were eight IBM (72.7%). Partial remission was obtained in 5/11 patients (45.5%), the disease was stable in 6/11 patients (54.5%) no complete remission was obtained nor regression of DHS/CC. The analysis of IM patients with inaugural DHS/CC delineates two groups of patients according to the age at first symptoms in terms of clinical and outcome specificities, and proposes an adapted diagnostic and care management approach to prevent long-term complications.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-09-2021
Publisher: Oxford University Press (OUP)
Date: 30-08-2023
Publisher: Oxford University Press (OUP)
Date: 06-10-2022
DOI: 10.1093/RHEUMATOLOGY/KEAC556
Abstract: Idiopathic inflammatory myopathies are mainly defined by inflammatory infiltrates within the muscle (lymphocytes and macrophages). Eosinophil muscle infiltration has been described in idiopathic eosinophilic myositis (IEM) and rarely in EF. This study aimed to further delineate the nosological frame of idiopathic eosinophil muscle infiltration through the exhaustive analysis of IEM and EF patients. This multicentre retrospective case series included IEM patients diagnosed between 2000 and 2022. IEM inclusion criteria were eosinophilic muscle infiltration with myositis pathological features, after the exclusion of differential diagnoses. An additional group of EF patients diagnosed between 2016 and 2022 was constituted. Inclusion criteria were an EF diagnosis and fascia thickening with inflammatory infiltrate. A total of 20 IEM cases and 10 EF cases were included. The median (interquartile range) age at diagnosis was 65 (49–70) years there were 18 males. Data analysis delineated four subgroups: focal EM (FEM, n = 3), diffuse EM (DEM, n = 6), eosinophilic myofasciitis (EMF, n = 11) and EF (n = 10). FEM represented a limited and benign form of myositis. DEM cases presented objective muscle impairment with eosinophilic muscle infiltration. EMF patients presented subjective muscle impairment (myalgia, 55%), fasciitis (on histology and/or imaging), eosinophilic muscle infiltration and frequent hypereosinophilia (55%). EF patients presented myalgia (50%), muscle lesions on histology with fascia-restricted inflammatory infiltrates with (60%) or without (40%) eosinophils. The analysis of IEM and EF patient characteristics delineates four subgroups (FEM, DEM, EMF and EF) in terms of clinical, laboratory, imaging, pathological and outcome specificities, and proposes an adapted diagnostic and care management approach.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2018
DOI: 10.1097/BOR.0000000000000555
Abstract: Antisynthetase syndrome (ASyS) is an acquired myopathy characterized by the presence of myositis-specific autoantibodies directed against tRNA-synthetases. ASyS is potentially life threatening due to lung involvement and treatment remains a challenge to date. With symptoms not limited to muscles but also involving lung, skin and joints, ASyS appears specific and has a particular pathogenesis, different from the other inflammatory myopathies. This review is intended to discuss the current understanding of ASyS pathogenesis, pointing its current knowledge and also the crucial prospects that may lead to critical improvement of ASyS care. Regarding ASyS pathogenesis, initiation of the disease seems to arise in a multifactorial context, with first lesions occurring within the lungs. This may lead to aberrant self-antigen exposure and tolerance breakdown. The consequences are abnormal activation of both innate and adaptive immunity, resulting in the patients with favourable genetic background to autoimmune-mediated organ lesions. Immune and nonimmune roles of the antigen, as well as antigen presentation leading to specific T-cell and B-cell activation and to the production of specific autoantibodies belong to the disease process. This work aims to detail ASyS pathogenesis understanding, from initiation to the disease propagation and target tissue lesions, in order to considering future treatment directions.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2019
DOI: 10.1097/BOR.0000000000000653
Abstract: The present review describes the interferon (IFN)-signature currently emerging as a tool for the diagnosis of idiopathic inflammatory myopathies (IIMs), and aims at presenting the interests and limitations of this recent tool for the clinics and the research. Recent in-vivo and in-vitro transcriptomic studies have evidenced the involvement of IFNs in the pathogenesis of IIMs. A correlation between the IFN-signature and the clinical severity of IIMs has been established. Moreover, studies pointed out differences in the IFN-signature regarding the IIM subgroup (dermatomyositis, polymyositis, inclusion body myositis, anti-synthetase syndrome, immuno-mediated necrotizing myopathies), raising the hypothesis of several pathogenic processes in IIMs. IIM pathogenesis remains partially understood. IFN-signature represents one of the main recent advances in the field. IFN-signature was identified thanks to transcriptomic analyses of tissues or cells from IIM patients (muscle, skin, blood cells, muscle cells) and should allow to establish new diagnosis and better monitoring of IIM patients. It also provides a tool for investigation of IIM pathogenesis. Nevertheless, IFN-signature still requires accurate definition in order to standardize its use, notably in the clinical practice.
Publisher: Elsevier BV
Date: 08-2021
Location: France
Location: France
No related grants have been discovered for Gallay Laure.