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1. Hematological malignancies in giant cell arteritis: a french population-based study

Author

Bernard Bonnotte, Georges Tarris, André Ramon, Maxime Samson, Morgane Mounier, Sylvain Audia, Marc Maynadié, Hélène Greigert, Louis Arnould, Catherine Creuzot-Garcher, Laurent Martin, Tibor Ponnelle, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Service de médecine interne et immunologie clinique (SOC 1) [CHU de Dijon], Laboratoire d'Excellence : Lipoprotéines et Santé : prévention et Traitement des maladies Inflammatoires et du Cancer (LabEx LipSTIC), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Gustave Roussy (IGR)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-Université de Montpellier (UM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Registre des hémopathies malignes de Côte d'Or, Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Ophtalmologie (CHU de Dijon), Cypath [Dijon], Cypath : siège social [Villeurbanne], Service d'hématologie biologique (CHU de Dijon), Julien, Sabine, and Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement

Subjects
Male, 0301 basic medicine, medicine.medical_specialty, Myeloid, Population, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, immune system diseases, Internal medicine, Epidemiology, medicine, Humans, Pharmacology (medical), cardiovascular diseases, hematological malignancies, [SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs, education, skin and connective tissue diseases, Retrospective Studies, 030203 arthritis & rheumatology, education.field_of_study, business.industry, giant cell arteritis, Incidence, Incidence (epidemiology), Middle Aged, medicine.disease, 3. Good health, Population based study, Giant cell arteritis, 030104 developmental biology, medicine.anatomical_structure, Increased risk, [SDV.MHEP.OS] Life Sciences [q-bio]/Human health and pathology/Sensory Organs, population-based study, Hematologic Neoplasms, cardiovascular system, Female, France, business
Abstract

Objectives An increased risk of haematological malignancies (HM) has been reported in GCA patients. Our study aimed to investigate the incidence and the type of HM occurring in GCA. Methods All patients with GCA and HM living in Côte d’Or (France) were identified by crossing data from the RHEMCO (Registre des Hémopathies Malignes de Côte d’Or) and those having a positive temporal artery biopsy between 1 January 2001 and 31 December 2018. Results Among 276 biopsy-proven GCA patients, 14 HM were identified in 12 patients (4.3%). In comparison with the general population aged >50 y, the incidence of myeloid HM and myeloproliferative syndromes were increased in GCA patients [standardized incidence ratios (SIR) = 2.71 and 5.16, respectively], with a specific increase in men with GCA (SIR = 4.82 and 9.04, respectively) but not in women. In addition, the study of SIR depending on the chronology between GCA and HM diagnoses suggests that there was an increased risk of developing GCA in men but not in women, after a diagnosis of myeloid HM (SIR = 9.56), especially if it was a MPS (SIR = 17.56). Conclusions Our study shows a particular epidemiology of HM in GCA patients, which is characterized by an increased incidence of myeloid HM, especially MPS, in male GCA patients. The chronology of the diagnoses of GCA and HM raises the hypothesis that clonal hematopoiesis may be implicated in some cases of GCA.

Published
2021

2. Mucosal-associated invariant T cells in giant cell arteritis

Author

Philippe Saas, Sylvain Audia, Claire Gerard, Bernard Bonnotte, Hélène Greigert, Claudie Cladière, T. Ghesquiere, Pierre-Henry Gabrielle, André Ramon, Maxime Samson, Coraline Genet, François Maurier, Georges Tarris, Catherine Creuzot-Garcher, Valérie Quipourt, Paul Ornetti, Hervé Devilliers, Marion Ciudad, Laurent Martin, Agnès Soudry-Faure, Marine Thébault, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Université Bourgogne Franche-Comté [COMUE] (UBFC), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Hospital Belle Isle, Service de Rhumatologie (CHU de Dijon), Plateforme d’Investigation Technologique [Centre d’Investigation Clinique 1432 module Plurithématique - Dijon] (PIT), Cognition, Action, et Plasticité Sensorimotrice [Dijon - U1093] (CAPS), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre d'Investigation Clinique 1432 (Dijon) - Module Plurithématique : Périnatalité Cancérologie Handicap et Ophtalmologie (CIC-P803), Université de Bourgogne (UB)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Ophtalmologie (CHU de Dijon), Délégation à la recherche clinique et à l'innovation [CHU Dijon] (DRCI), Centre d'Investigation Clinique de Besançon (Inserm CIC 1431), Université de Franche-Comté (UFC), and Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])

Subjects
Male, [SDV.OT]Life Sciences [q-bio]/Other [q-bio.OT], Proliferation index, CD3, Biopsy, Immunology, Primary Cell Culture, Stimulation, Mucosal associated invariant T cell, Mucosal-Associated Invariant T Cells, Flow cytometry, Pathogenesis, Tissue Culture Techniques, 03 medical and health sciences, Interferon-gamma, 0302 clinical medicine, medicine, Immunology and Allergy, Humans, Prospective Studies, Cells, Cultured, 030304 developmental biology, Aged, Cell Proliferation, 030203 arthritis & rheumatology, 0303 health sciences, medicine.diagnostic_test, biology, business.industry, giant cell arteritis, Interleukin-18, invariant t-cells, CD28, Middle Aged, medicine.disease, Interleukin-12, Healthy Volunteers, Temporal Arteries, Giant cell arteritis, mucosal associated invariant T, Case-Control Studies, biology.protein, Female, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Signal Transduction
Abstract

International audience; This study aimed to assess the implication of mucosal-associated invariant T (MAIT) cells in GCA. Blood samples were obtained from 34 GCA patients (before and after 3 months of treatment with glucocorticoids (GC) alone) and compared with 20 controls aged >50 years. MAIT cells, defined by a CD3(+)CD4(-)TCRγδ(-)TCRVα7.2(+)CD161(+) phenotype, were analyzed by flow cytometry. After sorting, we assessed the ability of MAIT cells to proliferate and produce cytokines after stimulation with anti CD3/CD28 microbeads or IL-12 and IL-18. MAIT were stained in temporal artery biopsies (TAB) by confocal microscopy. MAIT cells were found in the arterial wall of positive TABs but was absent in negative TAB. MAIT frequency among total αβ-T cells was similar in the blood of patients and controls (0.52 vs. 0.57%; P = 0.43) and not modified after GC treatment (P = 0.82). Expression of IFN-γ was increased in MAIT cells from GCA patients compared to controls (44.49 vs. 32.9%; P = 0.029), and not modified after 3 months of GC therapy (P = 0.82). When they were stimulated with IL-12 and IL-18, MAIT from GCA patients produced very high levels of IFN-γ and displayed a stronger proliferation compared with MAIT from controls (proliferation index 3.39 vs. 1.4; P = 0.032). In GCA, the functional characteristics of MAIT cells are modified toward a pro-inflammatory phenotype and a stronger proliferation capability in response to IL-12 and IL-18, suggesting that MAIT might play a role in GCA pathogenesis. Our results support the use of treatments targeting IL-12/IL-18 to inhibit the IFN-γ pathway in GCA.

Published
2021

3. Diagnostic performance of sacroiliac and spinal MRI for the diagnosis of non-radiographic axial spondyloarthritis in patients with inflammatory back pain

Author

André Ramon, Paul Ornetti, Romaric Loffroy, Christine Fayolle, Inès Herrada, Frank Verhoeven, Grégoire Attané, Hervé Devilliers, Equipe IFTIM [ImViA - EA7535], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Imagerie et Vision Artificielle [Dijon] (ImViA), and Université de Bourgogne (UB)-Université de Bourgogne (UB)

Subjects
musculoskeletal diseases, medicine.medical_specialty, Radiography, [SDV]Life Sciences [q-bio], Likelihood ratios in diagnostic testing, Sensitivity and Specificity, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Metaplasia, Spondylarthritis, Medicine, Humans, 030212 general & internal medicine, Prospective Studies, Medical diagnosis, Prospective cohort study, ComputingMilieux_MISCELLANEOUS, 030203 arthritis & rheumatology, Sacroiliac joint, business.industry, Sacroiliac Joint, Magnetic Resonance Imaging, Posterior segment of eyeball, medicine.anatomical_structure, Radiology, medicine.symptom, business, Low Back Pain
Abstract

Objective The lack of specificity of the ASAS MRI criteria for non-radiographic axial spondylarthritis (NR-axSpA) justifies the evaluation of the discriminatory capacity of other MRI abnormalities in the sacroiliac joints and dorsolumbar spine. Methods In patients hospitalized for inflammatory lumbar back pain, the diagnostic performance (sensitivity, specificity, positive likelihood ratio (PLR)) of MRI abnormalities was calculated using the rheumatologist expert opinion as a reference: (i) sacroiliac joints: Bone marrow edema (BME) (number and location), extended edema > 1 cm (deep lesion), fatty metaplasia (number), erosion (number and location), backfill. (ii) Dorsolumbar spine: BME (number and location), fatty metaplasia (number), posterior segment involvement. Results In this prospective cohort, 40 NR-axSpA cases and 79 other diagnoses were included. The presence of at least 3 inflammatory signals in the sacroiliac joints (PLR: 25.67 [95% CI: 3.48–48.9]), the presence of at least one sacroiliac erosion (PLR: 12.80 [3.04–54]), the combination of an inflammatory signal and sacroiliac erosion (PLR: 11.85 [2.79–50]), the combination of deep lesion and fatty metaplasia (PLR: 15.80 [2.05–121.9]) or erosion (PLR: 11.86 [1.47–95.01]) had the best diagnostic performance. The combination of spinal and sacroiliac MRI criteria significantly increased diagnostic performance for the diagnosis of NR-axSpA. Conclusion When NR-axSpA is suspected, in addition to the presence and number of inflammatory lesions, MRI interpretation should include the location and the extent of the sacroiliac lesions, the presence of erosion or fatty metaplasia, and anterior involvement of the lumbar spine.

Published
2021

4. Role of dual-energy CT in the diagnosis and follow-up of gout: systematic analysis of the literature

Author

Pierre Pottecher, Pascal Richette, Hervé Devilliers, André Ramon, Paul Ornetti, Jean-Francis Maillefert, Amélie Bohm-Sigrand, Service de Rhumatologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de radiologie et d'Imagerie médicale diagnostique et thérapeutique (CHU de Dijon), Laboratoire d'Electronique, d'Informatique et d'Image [EA 7508] (Le2i), Université de Technologie de Belfort-Montbeliard (UTBM)-Université de Bourgogne (UB)-École Nationale Supérieure d'Arts et Métiers (ENSAM), Arts et Métiers Sciences et Technologies, HESAM Université (HESAM)-HESAM Université (HESAM)-Arts et Métiers Sciences et Technologies, HESAM Université (HESAM)-HESAM Université (HESAM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot - Paris 7 (UPD7), Biologie de l'Os et du Cartilage : Régulations et Ciblages Thérapeutiques (BIOSCAR (UMR_S_1132 / U1132)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Rhumatologie [CHU Lariboisière], Hôpital Lariboisière, Cognition, Action, et Plasticité Sensorimotrice [Dijon - U1093] (CAPS), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Médecine Interne (SOC 1 et SOC 2) [CHU de Dijon], Centre d'Investigation Clinique 1432 (Dijon) - Module Plurithématique : Périnatalité Cancérologie Handicap et Ophtalmologie (CIC-P803), Institut National de la Santé et de la Recherche Médicale (INSERM)-Direction Générale de l'Organisation des Soins (DGOS)-Université de Bourgogne (UB), Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Université de Bourgogne (UB)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
musculoskeletal diseases, medicine.medical_specialty, Computed-Tomography, Identification, Gout, Radiography, MEDLINE, Systematic analysis Joint Fluid Analysis, Severity of Illness Index, Crystals, 030218 nuclear medicine & medical imaging, Imaging, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Internal medicine, Severity of illness, Synovial-Fluid, Ultrasound, Validation, medicine, Synovial fluid, Humans, 030203 arthritis & rheumatology, Reproducibility, business.industry, Arthritis, Tophus, General Medicine, medicine.disease, Classification, 3. Good health, Psychometric properties, Dual-energy CT, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Disease Progression, Radiology, business, Tomography, X-Ray Computed, Urate Deposition
Abstract

International audience; The aim of this systematic review was to determine the potential role of dual-energy CT in the diagnosis and follow-up of gout with regard to the Outcome Measures in Rheumatology (OMERACT) filter. A systematic analysis of the literature was conducted using the MEDLINE and Cochrane databases and published abstracts of international congresses, according to the criteria of the OMERACT filter: feasibility, reproducibility, validity versus laboratory (serum urate, MSU synovial fluid aspirate) and other imaging modalities for gout, and its sensitivity to change in patients on urate lowering therapy (ULT). Thirty-two articles were found representing a total of 1502 patients. The data on feasibility showed that the examination took little time and involved low levels of radiation but had current limited availability. Intra- and inter-observer reproducibility was excellent, with intra-class correlation coefficients > 0.9. Validity in comparison with polarized-light microscopy showed good sensitivity and specificity (> 80%). The diagnostic performance was better than that of radiography and conventional CT-scan and at least equivalent to that of ultrasonography. The sensitivity to change varied with effect sizes from 0.05 (low) to 1.24 (high) for decrease in the tophus volume following different ULT in gout patients. Dual-energy CT-scan is a reproducible and accurate imaging modality for the diagnosis of gout, particularly for tophaceous gout (intra- or extra-articular). It can become a second-line imaging modality of choice in cases of diagnostic doubt, such as ultrasonography. Its role remains uncertain in the follow-up of gout patients treated with ULT and needs further clarification.

Published
2018

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