Team leader : Olivier Benveniste
The team lead by Prof. Olivier Benveniste is committed to perform translational medicine studies focused on muscle immunology (including primary inflammatory myopathies (myositis), and immune responses elicited by enzyme replacement therapy procedures targeting muscle lysosomial diseases).
Auto-immune myopathies are a rare and heterogeneous acquired muscle diseases since both muscular and extra-muscular manifestations may differ, leading to identify subgroups of patients based on clinical phenotype and muscle pathology. Life-threatening complications still exist. The pathophysiology of these disabling diseases remains largely unknown. To date, most of these auto-immune myopathies are associated with newly described myositis specific auto-antibodies (MSA). Whereas each MSA is associated with a relatively homogenous clinical phenotype, nothing is known concerning the specificity of muscle pathology associated with a given MSA. In addition, the specificity of muscular immune response associated with a given MSA is not described as well.
Our goal is to revisit the classification, physiopathology and then treatment of the different inflammatory myopathies based on their MSA.
To achieve this goal and since the opening of the team, we have setting-up an e-CRF for myositis. We established the ethical management rules and obtained approval from ethical committee and CCTIRS. We launched this e-CRF in our center but also in 8 other centers in France. We started to perform patient characterization and phenotyping (998 patients are in the database in April 2015, and for 230 of them we already completed clinical/biological notably serological/imaging/pathology parameters). We hired a PhD student with a project in epidemiology to feed and analyse this database. In parallel, we established sample banking in “Myosites ADN-ARNthèque Serothèque Cellulothèque” (MASC study) (reference Codecoh: DC-2011-1445). Using these tools, we sharply characterize inflammatory responses of patients, effects of MSA on myoblasts primary cultures / tubes, or in vivo on mouse.
Lysosomial diseases and immune reactions elicited by enzyme replacement therapies
Pompe disease (PD) is an inherited metabolic myopathy caused by a deficiency of the lysosomal enzyme acid α-glucosidase (GAA). Enzyme replacement therapy (ERT) has improved the outcome of PD, however immune responses directed against infused recombinant GAA are not uncommon and in some cases prevent therapeutic efficacy. While it is clear that the development neutralizing antibodies to GAA is associated with a poor prognosis in infantile PD patients, in subjects with the milder form of the disease, the late-onset Pompe diseases (LOPD), immunity against GAA in ERT is poorly characterized both from an immunological and a clinical perspective.
The aim of the current study is to better characterize T cell responses to recombinant GAA in LOPD subjects with high vs. low antibody titers to the protein and to compare results in untreated LOPD subjects and healthy donors.
A similar approach is applied in Fabry disease, another lysosomal disorder eligible for ERT.
Olivier Benveniste, PU-PH, Team leader, Head of the Department of Internal Medicine et Clinical Immunology, Myositis National Network Coordinator
Yves Allenbach, MCU-PH, Co-team leader
Pascal Laforet, PH, Pompe disease National Network Coordinator
Olivier Lidove, PH, Fabry disease National Network Coordinator
Damien Amelin, Ingeneer
Akinori Uruha, Post-doc
Leandro Ladislau, Post-doc
Gaelle Dzangue-Tchoupou, Pre-doc
Kubéraka Mariampillai, Pre-doc
Wladimir Mauhin, Pre-doc
- Physical Activity Monitoring: A Promising Outcome Measure in Idiopathic Inflammatory Myopathies. Bachasson D, Landon-Cardinal O, Benveniste O, Hogrel JY, Allenbach Y. Neurology. 2017 May 31. pii: 10.1212/WNL.0000000000004061.
- Anti-mitochondrial antibodies are not a hallmark of severity in idiopathic inflammatory myopathies. Mauhin W, Mariampillai K, Allenbach Y, Charuel JL, Musset L, Benveniste O. Joint Bone Spine. 2017 Apr 20. pii: S1297-319X(17)30080-5. doi: 10.1016/j.jbspin.2017.04.004.
- Pathogenic role of anti-signal recognition protein and anti-3-Hydroxy-3-methylglutaryl-CoA reductase antibodies in necrotizing myopathies: Myofiber atrophy and impairment of muscle regeneration in necrotizing autoimmune myopathies. Arouche-Delaperche L, Allenbach Y, Amelin D, Preusse C, Mouly V, Mauhin W, Tchoupou GD, Drouot L, Boyer O, Stenzel W, Butler-Browne G, Benveniste O. Ann Neurol. 2017 Apr;81(4):538-548. doi: 10.1002/ana.24902.
- Cytosolic 5′-nucleotidase 1A autoantibody profile and clinical characteristics in inclusion body myositis. Lilleker JB, Rietveld A, Pye SR, Mariampillai K, Benveniste O, Peeters MT, Miller JA, Hanna MG, Machado PM, Parton MJ, Gheorghe KR, Badrising UA, Lundberg IE, Sacconi S, Herbert MK, McHugh NJ, Lecky BR, Brierley C, Hilton-Jones D, Lamb JA, Roberts ME, Cooper RG, Saris CG, Pruijn GJ, Chinoy H, van Engelen BG; all UKMYONET contributors. Ann Rheum Dis. 2017 May;76(5):862-868. doi: 10.1136/annrheumdis-2016-210282.
- Resistant myasthenia gravis and rituximab: A monocentric retrospective study of 28 patients. Afanasiev V, Demeret S, Bolgert F, Eymard B, Laforêt P, Benveniste O. Neuromuscul Disord. 2017 Mar;27(3):251-258. doi: 10.1016/j.nmd.2016.12.004. Epub 2016 Dec 14.
- Integrated classification of inflammatory myopathies. Allenbach Y, Benveniste O, Goebel HH, Stenzel W. Neuropathol Appl Neurobiol. 2017 Feb;43(1):62-81. doi: 10.1111/nan.12380. Review.
- Long-term exposure to Myozyme results in a decrease of anti-drug antibodies in late-onset Pompe disease patients. Masat E, Laforêt P, De Antonio M, Corre G, Perniconi B, Taouagh N, Mariampillai K, Amelin D, Mauhin W, Hogrel JY, Caillaud C, Ronzitti G, Puzzo F, Kuranda K, Colella P, Mallone R, Benveniste O, Mingozzi F; French Pompe Registry Study Group. Sci Rep. 2016 Nov 4;6:36182. doi: 10.1038/srep36182.
- [Usefulness of rehabilitation in inflammatory myopathies]. Moyon Q, Benveniste O. Rev Med Interne. 2016 Nov;37(11):751-758. doi: 10.1016/j.revmed.2016.08.004. Epub 2016 Sep 9. Review. French.
- Advances in serological diagnostics of inflammatory myopathies. Benveniste O, Stenzel W, Allenbach Y. Curr Opin Neurol. 2016 Oct;29(5):662-73. doi: 10.1097/WCO.0000000000000376.
- Involvement of NK Cells and NKp30 Pathway in Antisynthetase Syndrome. Hervier B, Perez M, Allenbach Y, Devilliers H, Cohen F, Uzunhan Y, Ouakrim H, Dorgham K, Méritet JF, Longchampt E, Stenzel W, Cremer I, Benveniste O, Vieillard V. J Immunol. 2016 Sep 1;197(5):1621-30. doi: 10.4049/jimmunol.1501902. Epub 2016 Aug 10.
- 213th ENMC International Workshop: Outcome measures and clinical trial readiness in idiopathic inflammatory myopathies, Heemskerk, The Netherlands, 18-20 September 2015. Benveniste O, Rider LG; ENMC Myositis Outcomes Study Group. Neuromuscul Disord. 2016 Aug;26(8):523-34. doi: 10.1016/j.nmd.2016.05.014.
- Differential roles of hypoxia and innate immunity in juvenile and adult dermatomyositis. Preuße C, Allenbach Y, Hoffmann O, Goebel HH, Pehl D, Radke J, Doeser A, Schneider U, Alten RH, Kallinich T, Benveniste O, von Moers A, Schoser B, Schara U, Stenzel W. Acta Neuropathol Commun. 2016 Apr 27;4(1):45. doi: 10.1186/s40478-016-0308-5.
- High risk of cancer in autoimmune necrotizing myopathies: usefulness of myositis specific antibody. Allenbach Y, Keraen J, Bouvier AM, Jooste V, Champtiaux N, Hervier B, Schoindre Y, Rigolet A, Gilardin L, Musset L, Charuel JL, Boyer O, Jouen F, Drouot L, Martinet J, Stojkovic T, Eymard B, Laforêt P, Behin A, Salort-Campana E, Fain O, Meyer A, Schleinitz N, Mariampillai K, Grados A, Benveniste O. Brain. 2016 Aug;139(Pt 8):2131-5. doi: 10.1093/brain/aww054. Epub 2016 Apr 17.
- Dermatomyositis With or Without Anti-Melanoma Differentiation-Associated Gene 5 Antibodies: Common Interferon Signature but Distinct NOS2 Expression. Allenbach Y, Leroux G, Suárez-Calvet X, Preusse C, Gallardo E, Hervier B, Rigolet A, Hie M, Pehl D, Limal N, Hufnagl P, Zerbe N, Meyer A, Aouizerate J, Uzunhan Y, Maisonobe T, Goebel HH, Benveniste O, Stenzel W; French Myositis Network. Am J Pathol. 2016 Mar;186(3):691-700. doi: 10.1016/j.ajpath.2015.11.010. Epub 2016 Jan 21.
- Efficacy of Rituximab in Refractory Inflammatory Myopathies Associated with Anti- Synthetase Auto-Antibodies: An Open-Label, Phase II Trial. Allenbach Y, Guiguet M, Rigolet A, Marie I, Hachulla E, Drouot L, Jouen F, Jacquot S, Mariampillai K, Musset L, Grenier P, Devilliers H, Hij A, Boyer O, Herson S, Benveniste O. PLoS One. 2015 Nov 5;10(11):e0133702. doi: 10.1371/journal.pone.0133702. eCollection 2015.
- Anti-Jo-1 antibody-positive patients show a characteristic necrotizing perifascicular myositis. Mescam-Mancini L, Allenbach Y, Hervier B, Devilliers H, Mariampillay K, Dubourg O, Maisonobe T, Gherardi R, Mezin P, Preusse C, Stenzel W, Benveniste O. Brain. 2015 Sep;138(Pt 9):2485-92. doi: 10.1093/brain/awv192. Epub 2015 Jul 21.