Publications by authors named "Florence Bucciarelli"

10 Publications

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Sunlight exposure exerts immunomodulatory effects to reduce multiple sclerosis severity.

Proc Natl Acad Sci U S A 2021 Jan;118(1)

Department of Neurology with Institute of Translational Neurology, University of Muenster, 48149 Muenster, Germany;

Multiple sclerosis (MS) disease risk is associated with reduced sun-exposure. This study assessed the relationship between measures of sun exposure (vitamin D [vitD], latitude) and MS severity in the setting of two multicenter cohort studies ( = 946, = 990). Additionally, effect-modification by medication and photosensitivity-associated variants was assessed. High serum vitD was associated with a reduced MS severity score (MSSS), reduced risk for relapses, and lower disability accumulation over time. Low latitude was associated with higher vitD, lower MSSS, fewer gadolinium-enhancing lesions, and lower disability accumulation. The association of latitude with disability was lacking in IFN-β-treated patients. In carriers of :rs1805008(T), who reported increased sensitivity toward sunlight, lower latitude was associated with higher MRI activity, whereas for noncarriers there was less MRI activity at lower latitudes. In a further exploratory approach, the effect of ultraviolet (UV)-phototherapy on the transcriptome of immune cells of MS patients was assessed using samples from an earlier study. Phototherapy induced a vitD and type I IFN signature that was most apparent in monocytes but that could also be detected in B and T cells. In summary, our study suggests beneficial effects of sun exposure on established MS, as demonstrated by a correlative network between the three factors: Latitude, vitD, and disease severity. However, sun exposure might be detrimental for photosensitive patients. Furthermore, a direct induction of type I IFNs through sun exposure could be another mechanism of UV-mediated immune-modulation in MS.
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http://dx.doi.org/10.1073/pnas.2018457118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817192PMC
January 2021

BEST-MS: A prospective head-to-head comparative study of natalizumab and fingolimod in active relapsing MS.

Mult Scler 2020 Oct 30:1352458520969145. Epub 2020 Oct 30.

Service de Neurologie, CRCSEP, Unité de Recherche Clinique Cote d'Azur (UR2CA), Centre Hospitalier Universitaire Pasteur 2, Nice, France.

Background: There are few head-to-head studies to compare highly active treatments in multiple sclerosis (MS).

Objective: The aim of this study was to compare the effectiveness between natalizumab (NTZ) and fingolimod (FTY) in active relapsing-remitting MS.

Method: Best Escalation STrategy in Multiple Sclerosis (BEST-MS) is a multicentric, prospective study with a 12-month follow-up including patients with active MS. Treatment choice was at the discretion of physician. Clinical and magnetic resonance imaging (MRI) data were collected at baseline and at 12 months. The primary outcome was the proportion of patients reaching no evidence of disease activity (NEDA) at 12 months. Secondary outcomes included annualized relapse rate and MRI activity.

Results: A total of 223 patients were included (NTZ: 109 and FTY: 114). Treatment groups were well balanced at baseline. Proportion of NEDA patients was 47.8% in NTZ group versus 30.4% in FTY group ( = 0.015). This superiority was driven by annualized relapse rate and MRI activity. In the multivariate analysis, treatment group was the only factor associated with NEDA at 12 months with a lower probability in FTY group (odds ratio (OR) = 0.49,  = 0.029).

Conclusion: BEST-MS is a prospective study that compared head-to-head the effectiveness of NTZ and FTY in active relapsing-remitting MS. Our results suggest a superiority of NTZ over FTY.
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http://dx.doi.org/10.1177/1352458520969145DOI Listing
October 2020

Prospective validation of the PML risk biomarker l-selectin and influence of natalizumab extended intervals.

Neurology 2019 09 22;93(12):550-554. Epub 2019 Aug 22.

From the Department of Neurology with Institute of Translational Neurology (N.S., T.S.-H., P.O., L.K., C.C.G., S.G.M., H.W.), University of Münster, Münster, Germany; CRC-SEP-Neurosciences Department (B.P., F.B., L.S., J.C., D. Biotti, D. Brassat), CHU Toulouse, Toulouse, France; CPTP-INSERM U1043-CNRS U5282-Université Toulouse III (B.P., F.B., L.S., D. Brassat), Toulouse, France; APHM (C.L.-F.), Hôpital de la Timone, Pôle de Neurosciences Cliniques, Marseille, France; CHU of Nice (G.M.), Nice, France; CHU Montpied, Neurology, Clermont-Ferrand, France (P.C.); APHM (J.P.), Hôpital de la Timone, Pôle de Neurosciences Cliniques, Service de Neurologie, CRCSEP Marseille, France; Institute of Clinical Neuroimmunology (I.M.), Ludwig-Maximilians University, Munich, Germany; Department of Neurology (S.W.), Clinics Osnabrück, Osnabrück, Germany; and Department of Neurology (F.G.), Innsbruck Medical University, Innsbruck, Austria.

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http://dx.doi.org/10.1212/WNL.0000000000008135DOI Listing
September 2019

CD62L test at 2 years of natalizumab predicts progressive multifocal leukoencephalopathy.

Neurology 2016 12 4;87(23):2491-2494. Epub 2016 Nov 4.

From the CHU Toulouse Purpan (B.P., F.B., D.B., D.A.-P., D.B.), Pôle Neurosciences; INSERM U1043-CNRS UMR 5282 (B.P., F.B., D.B.), Université Toulouse III, Centre de Physiopathologie Toulouse Purpan, France; University of Münster (N.S., T.S.-H., H.W.), Germany; University of Lille (O.O., H.Z., P.V.); Hôpital Civil (J.-C. Ongagna, J.d.S.), Strasbourg; CHU Pellegrin (B.B., J.-C. Ouallet), Bordeaux; CHU Nancy (M.D., S.P.); CHU Caen (G.D., N.D.); CH St Vincent (P.H.), GHICL, Lille; CHU Reims (A.T.); CHU Montpellier (P.L.); CHU Nîmes (G.C., W.C., O.C.); CHRU Clermont Ferrand (P.C.); CHU Besançon (E.B.); Aix Marseille University (J.P., A.R.), APHM, CHU Timone, Marseille; CHU Nantes (D.L., S.W.); CHU Grenoble (E.T.); CHU Dijon (T.M., A.F.); CHU Lyon (S.V.), Bron; Hôpital de la Salpêtrière (C.P.), Paris, France; Centre d'Esclerosi Múltiple de Catalunya (CEMCAT) (M.C.), Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Spain; and CHU Nice (C.L.-F.), France.

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http://dx.doi.org/10.1212/WNL.0000000000003401DOI Listing
December 2016

Interleukin 17 alone is not a discriminant biomarker in early demyelinating spectrum disorders.

J Neurol Sci 2016 Sep 25;368:334-6. Epub 2016 Jul 25.

Neurology, Hopital Purpan, Toulouse, France.

Background: Radiologically isolated syndrome (RIS) is a sub clinical demyelinating neurological disorder and to date no biomarker that triggers the seminal event has been identified. As for multiple sclerosis (MS), disease activity and clinical course are unpredictable. In MS, exploratory studies reported increased IL-17 levels in CSF but results in detecting IL-17 in serum at different stage of the disease are controversial.

Objectives: We investigate levels of IL-17 in serum and CSF in patients diagnosed at different stages of demyelinating diseases (RIS, CIS, relapsing remitting (RR) or active multiple sclerosis patients:AMS) as a marker of inflammatory condition.

Methods: 1417 sera has been tested for IL-17A (1177 from active MS, 80 RRMS, 35 RIS, 35 CIS, 10 IIH: idiopathic intracranial hypertension, and 80 controls) and 240 CSF from RIS, CIS, IIH and controls.

Results: No difference has been found between RIS who early clinically converted and CIS patients who rapidly evolve in McDonald or clinically definite MS, nor active MS. No correlation was found with usual MRI or CSF criteria.

Conclusion: Our results do not confirm that IL-17 can be considerate as a reliable marker of inflammation in the demyelinating spectrum disorders, either in blood or CSF.
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http://dx.doi.org/10.1016/j.jns.2016.07.052DOI Listing
September 2016

Fingolimod treatment after natalizumab-related progressive multifocal leukoencephalopathy: three new cases.

Mult Scler 2015 Apr 10;21(5):671-2. Epub 2014 Oct 10.

Pole des neurosciences CHU Toulouse, France INSERM UMR 1043 et Université de Toulouse; UPS; France

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http://dx.doi.org/10.1177/1352458514549823DOI Listing
April 2015

Tyrosine kinase 2 variant influences T lymphocyte polarization and multiple sclerosis susceptibility.

Brain 2011 Mar;134(Pt 3):693-703

INSERM U563 and Pôle des neurosciences, University of Toulouse 3, 31000 Toulouse, France.

The tyrosine kinase 2 variant rs34536443 has been established as a genetic risk factor for multiple sclerosis in a variety of populations. However, the functional effect of this variant on disease pathogenesis remains unclear. This study replicated the genetic association of tyrosine kinase 2 with multiple sclerosis in a cohort of 1366 French patients and 1802 controls. Furthermore, we assessed the functional consequences of this polymorphism on human T lymphocytes by comparing the reactivity and cytokine profile of T lymphocytes isolated from individuals expressing the protective TYK2(GC) genotype with the disease-associated TYK2(GG) genotype. Our results demonstrate that the protective C allele infers decreased tyrosine kinase 2 activity, and this reduction of activity is associated with a shift in the cytokine profile favouring the secretion of Th2 cytokines. These findings suggest that the rs34536443 variant effect on multiple sclerosis susceptibility might be mediated by deviating T lymphocyte differentiation toward a Th2 phenotype. This impact of tyrosine kinase 2 on effector differentiation is likely to be of wider importance because other autoimmune diseases also have been associated with polymorphisms within tyrosine kinase 2. The modulation of tyrosine kinase 2 activity might therefore represent a new therapeutic approach for the treatment of autoimmune diseases.
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http://dx.doi.org/10.1093/brain/awr010DOI Listing
March 2011

IFIH1-GCA-KCNH7 locus is not associated with genetic susceptibility to multiple sclerosis in French patients.

Eur J Hum Genet 2009 Jun 21;17(6):844-7. Epub 2009 Jan 21.

INSERM U563, and Pôle des neurosciences, Université Toulouse 3, Toulouse, France.

A recent investigation reported, for the first time, an association between variants in the IFIH1-GCA-KCNH7 locus and multiple sclerosis (MS). We sought to replicate this genetic association in MS with a new independent MS cohort composed of French Caucasian MS trio families. The two most significant IFIH1 single nucleotide polymorphisms, rs1990760 and rs2068330, reported as involved in MS susceptibility, were genotyped in 591 French Caucasian MS trio families, and analyzed using the transmission/disequilibrium test. No association with MS was found (rs1990760, P=0.45 and rs2068330, P=0.27). Similarly, no significant association was detected after stratification for HLA-DRB1*1501 carriers. Reasons that may explain this discrepancy between the original report and our study are discussed.
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http://dx.doi.org/10.1038/ejhg.2008.259DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2947096PMC
June 2009

CD8 T cell responses to myelin oligodendrocyte glycoprotein-derived peptides in humanized HLA-A*0201-transgenic mice.

J Immunol 2007 Oct;179(8):5090-8

Institut National de la Santé et de la Recherche Médicale, Unité 563, Centre de Physiopathologie de Toulouse Purpan, Toulouse, France.

Multiple sclerosis (MS) is a demyelinating inflammatory disease of the CNS. Though originally believed to be CD4-mediated, additional immune effector mechanisms, including myelin-specific CD8(+) T cells, are now proposed to participate in the pathophysiology of MS. To study the immunologic and encephalitogenic behavior of HLA-A*0201-binding myelin-derived epitopes in vivo, we used a humanized HLA-A*0201-transgenic mouse model. Eight HLA-A*0201-binding peptides derived from myelin oligodendrocyte glycoprotein (MOG), an immunodominant myelin self-Ag, were identified in silico. After establishing their relative affinity for HLA-A*0201 and their capacity to form stable complexes with HLA-A*0201 in vitro, their immunological characteristics were studied in HLA-A*0201-transgenic mice. Five MOG peptides, which bound stably to HLA-A*0201 exhibited strong immunogenicity by inducing a sizeable MOG-specific HLA-A*0201-restricted CD8(+) T cell response in vivo. Of these five candidate epitopes, four were processed by MOG-transfected RMA target cells and two peptides proved immunodominant in vivo in response to a plasmid-encoding native full-length MOG. One of the immunodominant MOG peptides (MOG(181)) generated a cytotoxic CD8(+) T cell response able to aggravate CD4(+)-mediated EAE. Therefore, this detailed in vivo characterization provides a hierarchy of candidate epitopes for MOG-specific CD8(+) T cell responses in HLA-A*0201 MS patients identifying the encephalitogenic MOG(181) epitope as a primary candidate.
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http://dx.doi.org/10.4049/jimmunol.179.8.5090DOI Listing
October 2007

Pertussis toxin reduces the number of splenic Foxp3+ regulatory T cells.

J Immunol 2006 Aug;177(3):1552-60

Institut National de la Santé et de la Recherche Médicale (INSERM) Unité 563, Centre de Physiopathologie de Toulouse Purpan, Toulouse, France.

Pertussis toxin (PTx) is a bacterial toxin used to enhance the severity of experimental autoimmune diseases such as experimental autoimmune encephalomyelitis. It is known to promote permeabilization of the blood-brain barrier, maturation of APC, activation of autoreactive lymphocytes and alteration of lymphocyte migration. In this study, we show that i.v. injection of PTx in mice induces a decrease in the number of splenic CD4(+)CD25(+) regulatory T cells (Treg cells). Furthermore, PTx not only induces a depletion of the dominant CD4(+)CD25(+)Foxp3(+) subpopulation of splenic Treg cells, but also reduces to a similar extent the CD4(+)CD25(-)Foxp3(+) subpopulation. On a per cell basis, the suppressive properties of the remaining Treg cells are not modified by PTx treatment. The reduction in splenic Treg cells is associated with preferential migration of these cells to the liver. Additionally, Treg cells exhibit a high sensitivity to PTx-mediated apoptosis in vitro. Finally, in vivo depletion of Treg cells by injection of an anti-CD25 Ab, and PTx treatment, present synergistic experimental autoimmune encephalomyelitis exacerbating effects. Therefore, we identify a new effect of PTx and provide an additional illustration of the influence of microbial components on the immune system affecting the balance between tolerance, inflammation and autoimmunity.
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http://dx.doi.org/10.4049/jimmunol.177.3.1552DOI Listing
August 2006