Jacques TEBIB

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Response in

and platelet factor 4 are biomarkers for infliximab

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FM in SpA Personal non-commercial use only

ABSTRACT. Objective. Spondyloarthritis (SpA) is the second most frequent inflammatory rheumatic d... more

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La fibrose apicale de la spondylarthrite ankylosante : apport de la clairance muco-ciliaire

Presse Medicale, 1988

Spondylites à Capnocytophaga

Nous rapportons la premiere localisation vertebrale d'une infection a Capnocytophaga chez un ... more Nous rapportons la premiere localisation vertebrale d'une infection a Capnocytophaga chez un sujet immunocompetent. Cette observation interesse une femme de 75 ans souffrant de lombalgies dans un contexte de baisse de l'etat general. Les radiographies standard objectivent une erosion du plateau superieur de L4 et du plateau inferieur de L3 avec integrite du disque intervertebral confirmee par l'IRM. Un deuxieme prelevement vertebral avec mise en culture bacteriologique en milieu riche en CO 2 est necessaire pour identifier le germe et obtenir la guerison. Ainsi, devant la suspicion d'une infection osseuse convient-il de rechercher une porte d'entree (Capnocytophaga sont des bacilles commensaux de la cavite buccale), de multiplier les prelevements et de faire une recherche bacteriologique aussi large que possible.

Lésion de la branche médiale du nerf fibulaire profond : données cliniques, échographiques et thérapeutiques de 78 pieds

Revue du Rhumatisme, 2018

Resume Objectif Etudier les symptomes de l’atteinte de la branche mediale du nerf fibulaire profo... more Resume Objectif Etudier les symptomes de l’atteinte de la branche mediale du nerf fibulaire profond et l’amelioration des signes fonctionnels apres traitement. Methodes Des patients avec une histoire clinique de troubles sensitifs d’irritation du nerf fibulaire profond ont ete successivement selectionnes par 3 praticiens orientes en pathologie du pied. Chaque pied presentait au moins un point gâchette sur le trajet du nerf a l’examen physique. Si l’atteinte etait confirmee par l’electromyogramme, le patient etait inclus dans l’etude. Une recherche de troubles de la sensibilite cutanee de la premiere commissure intermetatarsienne, une radiographie de profil en charge et une echographie etaient ensuite realisees pour chaque pied. Resultats Parmi les 78 pieds inclus presentant une atteinte de la branche mediale du nerf fibulaire profond confirmee par electroneuromyographie, 59 (76 %) presentaient un trouble sensitif de la premiere commissure intermetatarsienne et 34 (44 %) un pied creux. L’echographie retenait au moins un conflit avec le nerf sur 40 pieds (51 %). Trente des 59 pieds (51 %) presentant un trouble sensitif de la premiere commissure intermetatarsienne presentaient egalement un conflit en echographie. Le traitement conservateur a ete efficace sur 68/78 pieds, dont 31/40 (78 %) avec conflit. Dix pieds sur 78 (13 %) ont eu une liberation chirurgicale du nerf et 8/10 pieds ont ete ameliores par la chirurgie. Conclusion Ces resultats doivent inciter en pratique le rhumatologue a rechercher a l’examen clinique une souffrance de la branche mediale du nerf fibulaire profond.

Prealbumin, platelet factor 4 and S100A12 combination at baseline predicts good response to TNF alpha inhibitors in Rheumatoid Arthritis

Joint, bone, spine : revue du rhumatisme, Jan 6, 2018

Tumour necrosis factor-alpha inhibitors (TNFi) are effective treatments for Rheumatoid Arthritis ... more Tumour necrosis factor-alpha inhibitors (TNFi) are effective treatments for Rheumatoid Arthritis (RA). Responses to treatment are barely predictable. As these treatments are costly and may induce a number of side effects, we aimed at identifying a panel of protein biomarkers that could be used to predict clinical response to TNFi for RA patients. Baseline blood levels of C-reactive protein, platelet factor 4, apolipoprotein A1, prealbumin, α1-antitrypsin, haptoglobin, S100A8/A9 and S100A12 proteins in bDMARD naive patients at the time of TNFi treatment initiation were assessed in a multicentric prospective French cohort. Patients fulfilling good EULAR response at 6 months were considered as responders. Logistic regression was used to determine best biomarker set that could predict good clinical response to TNFi. A combination of biomarkers (prealbumin, platelet factor 4 and S100A12) was identified and could predict response to TNFi in RA with sensitivity of 78%, specificity of 77%, ...

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Variants of genes implicated in type 1 interferon pathway and B-cell activation modulate the EULAR response to rituximab at 24 weeks in rheumatoid arthritis

RMD open, 2017

The type 1 interferon (IFN) pathway has been identified to potentially affect the response to rit... more The type 1 interferon (IFN) pathway has been identified to potentially affect the response to rituximab (RTX) for rheumatoid arthritis (RA), which suggests the contribution of type 1 IFN pathway genes such as IFN regulatory factor 5 and 7 (IRF5 and IRF7), tyrosine kinase 2 (TYK2), signal transducer and activator of transcription 4 (STAT4) and osteopontin (SPP1). Our objective was to study functional variants of these IFN pathway genes as predictors of the European League Against Rheumatism (EULAR) response to RTX for RA at week 24 (W24). Logistic regression analysis with a stepwise multivariate model adjusted for sex, age and DAS28-CRP (Disease Activity Score in 28 joints with C reactive protein) in 115 patients from the SMART randomised studywas used to analyse the association between the candidate variants and W24 EULAR response. Because the variant TNFSF13B rs9514828 was previously found associated with RTX response in the same population, it was included in the analysis. The com...

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OP0237 Polymorphisms of Gene Implicated in Type 1 Interferon Pathway Are Associated with The Clinical Response of Rituximab at 24 Weeks in Rheumatoid Arthritis

Annals of the Rheumatic Diseases, 2016

Background Rheumatoid arthritis (RA) treatment may target B-cells using rituximab (RTX), a chimer... more Background Rheumatoid arthritis (RA) treatment may target B-cells using rituximab (RTX), a chimeric monoclonal antibody directed against the B-cell marker CD20. Transcriptome of PBMCs from RA patients before RTX has suggested that responders differs from non-responders on the expression of genes regulated by type 1 interferon (IFN) (1) suggesting a possible contribution of type 1 IFN pathway genes such as interferon regulatory factor 5 (IRF5), tyrosine kinase 2 (TYK2), signal transducer and activator of transcription 4 (STAT4), osteopontin (SPP1) and interferon regulatory factor 7 (IRF7). Objectives To study 8 IRF5, TYK2, STAT4, SPP1 and IRF7 variants as candidate predictors of the clinical response to RTX in RA at 6 months defined by a good or moderate EULAR response. Methods Patients from the SMART study who signed consent for genetic studies were included (2). The association between the EULAR response at 24 weeks and the polymorphism of the 8 chosen SNPs was analyzed by logistic regression. Response rates were compared across risk genotypes using the χ2 test or the Fisher exact test, when appropriate. Significant variables after univariate regression (P<0.15) were entered into a stepwise multivariate model adjusted to the sex, the age and the DAS28-CRP score. Results Among the 115 included patients, 92 were women, mean age was 56 years, 93 patients were anti-CCP positive. At M6, 30 patients were considered as good responders (26.1%), 62 as moderate responders (53.9%) and 22 as non-responders (19.1%). Univariate analysis showed that IRF5 rs2004640 was significantly associated with a good/moderate EULAR response at week 24 (P=0.038) whereas IRF7 rs1131665 and SPP1 rs9138 were near statistical significance (P=0.092 and P=0.089, respectively). Since it was previously reported an association between TNFSF13B (the gene coding the BAFF cytokine) rs9514828 and RTX response in RA in the same cohort (2), this variant was also included in the multivariate analysis. The multivariate analysis with logistic regression analysis including IRF5, SPP1, IRF7 and TNFSF13B revealed that a genotypic combination of IRF5 rs2004640, SPP1 rs9138 and TNFSF13B rs9514828 was strongly associated with good/moderate response to RTX at M6: P=9.34x10–6, OR =11.37 [4.03–35.28] with a PPV of 91% and a NPV of 53% (Fig. 1). Conclusions We found an association between a combination of type 1-interferon genes and response to RTX treatment in RA. To further validate the magnitude of the association detected an independent replication in a larger cohort is required. If validated, our model could be helpful before the decision of initiating RTX in RA. References Vosslamber S, et al. Ann Rheum Dis 2011. Ruyssen-Witrand A, et al. Rheumatology 2013. Acknowledgement Unrestricted grant from Roche-Chugai and SFR Disclosure of Interest None declared

Fibromyalgia in Spondyloarthritis: Effect on Disease Activity Assessment in Clinical Practice

The Journal of Rheumatology, 2016

Objective.Spondyloarthritis (SpA) is the second most frequent inflammatory rheumatic disease, cha... more Objective.Spondyloarthritis (SpA) is the second most frequent inflammatory rheumatic disease, characterized by spinal involvement, peripheral arthritis, or enthesitis with marked pain, stiffness, and fatigue. Fibromyalgia (FM) may be associated with SpA, and shares some common symptoms. We aimed to determine how FM influences assessment of SpA disease activity, which is mainly dependent on patient-based outcome measures such as the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) or the Ankylosing Spondylitis Disease Activity Score (ASDAS).Methods.This single-center cross-sectional study included consecutive patients with SpA according to the Assessment of SpondyloArthritis International Society criteria. FM was diagnosed according to the 1990 American College of Rheumatology criteria. Patient characteristics, BASDAI, ASDAS/C-reactive protein (CRP), Bath Ankylosing Spondylitis Functional Index, Bath Ankylosing Spondylitis Metrology Index, and the Medical Outcomes Study Sh...

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Isolated positive anti-SS-B autoantibodies are not related to clinical features of systemic autoimmune diseases: Results from a routine population survey

PLOS ONE, 2017

Objective To assess in clinical practice the frequency and diagnosis associated with the SS-B-pos... more Objective To assess in clinical practice the frequency and diagnosis associated with the SS-B-positive/SS-A negative autoantibody profile. Methods We analyzed a one-year consecutive population of 624 patients referred by clinicians to the immunology laboratory to investigate anti-SS-A and/or anti-SS-B autoantibodies, who were detected using luminex technology. Data were analyzed for patients with isolated anti-SS-B autoantibodies. The clinical characteristics and diagnosis of connective tissue diseases (CTD) were retrieved according to the international criteria. Results Among 1173 sera positive for anti-SS-A and/or anti-SS-B autoantibodies from 624 patients, we identified 84 patients (13.5%) that had isolated anti-SS-B. Among the 75 patients

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A bicentre retrospective study of features and outcomes of patients with reactive arthritis

Joint, bone, spine : revue du rhumatisme, Jan 24, 2017

Reactive arthritis (ReA) is a sterile arthritis following an extra-articular infection, usually o... more Reactive arthritis (ReA) is a sterile arthritis following an extra-articular infection, usually of the gastrointestinal or genitourinary tract. The aim of this study was to assess the incidence and the clinical and therapeutic characteristics of ReA and to compare them with those of a historical cohort. We hypothesised that improved hygiene together with prevention and treatment of sexually transmitted infections may have decreased the incidence of ReA. All patients with ReA diagnosed in the University Hospital Centres of Lyon Sud and Besançon from January 2002 to December 2012 were included in the study retrospectively and were compared with ReA patients diagnosed from January 1986 to December 1996 in the same two hospitals. Medical records were reviewed, clinical features, treatments and outcomes were analysed and diagnoses were compared with international diagnostic criteria. Twenty-seven patients were included between 2002 and 2012 compared with 31 between 1986 and 1996. The ove...

Variations in the metabolome in response to disease activity of rheumatoid arthritis

BMC musculoskeletal disorders, Aug 22, 2016

Anti-Tumor Necrosis Factor (TNF) therapies are able to control rheumatoid arthritis (RA) disease ... more Anti-Tumor Necrosis Factor (TNF) therapies are able to control rheumatoid arthritis (RA) disease activity and limit structural damage. Yet no predictive factor of response to anti-TNF has been identified. Metabolomic profile is known to vary in response to different inflammatory rheumatisms so determining it could substantially improve diagnosis and, consequently, prognosis. The aim of this study was to use mass spectrometry to determine whether there is variation in the metabolome in patients treated with anti-TNF and whether any particular metabolomic profile can serve as a predictor of therapeutic response. Blood samples were analyzed in 140 patients with active RA before initiation of anti-TNF treatment and after 6 months of Anti-TNF treatment (100 good responders and 40 non-responders). Plasma was deproteinized, extracted and analyzed by reverse-phase chromatography-QToF mass spectrometry. Extracted and normalized ions were tested by univariate and ANOVA analysis followed by pa...

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Mécanismes pathologiques : Le syndrome des antiphospholipides

La Lettre Du Rhumatologue, 2002

■ Les phospholipides membranaires sont peu immunogenes, mais ils sont souvent mis en contact avec... more ■ Les phospholipides membranaires sont peu immunogenes, mais ils sont souvent mis en contact avec le systeme immunitaire par le biais de processus courants physiologiques comme l'apoptose ou pathologiques comme la necrose. En revanche, ces memes phospholipides, associes a des cofacteurs proteiques impliques dans un grand nombre de fonctions physiologiques comme la coagulation, acquierent alors un fort pouvoir immunogene susceptible d'induire des anticorps de forte affinite. Ces proprietes expliquent bien la dualite rencontree dans la description de la pathologie induite par la formation des autoanticorps antiphospholipides avec des anticorps diriges contre le phospholipide isole, qui sont tres frequents et peu pathogenes, et des anticorps diriges contre le phospholipide associe, plus rares mais responsables des desordres rencontres. ■ Les phospholipides sont impliques en association avec des proteines dans un grand nombre de reactions physiologiques qui vont du maintien de la structure cellulaire aux processus de coagulation, en passant par le developpement du complexe foeto-placentaire. La production d'anticorps pathogenes dans ces differentes situations explique le caractere tres proteiforme du syndrome des APL.

Infection � cytom�galovirus chez un patient atteint de polyarthrite rhumato�de

Rev Rhum, 2003

Utilisation du méthotrexate dans la polyarthrite rhumatoïde : établissement de recommandations pour la pratique clinique à partir de données de la littérature et d'opinions d'experts

Revue Du Rhumatisme, 2005

Objectifs : developper des recommandations sur l'utilisation du methotrexate (MTX) dans la po... more Objectifs : developper des recommandations sur l'utilisation du methotrexate (MTX) dans la polyarthrite rhumatoide (PR) selon la methodologie de la medecine fondee sur les preuves (evidence based medicine - EBM) et l'opinion d'experts. Methodes : l'etude s'est deroulee en trois temps. 1. Choix de cinq questions par un comite scientifique selon la methode Delphi. 2. Revue de la litterature realisee a partir des bases de donnees Cochrane, Pubmed, congres de la SFR, de l'EULAR et de l'ACR. 3. Elaboration puis validation des recommandations par un groupe d'experts rhumatologues, en precisant le niveau de preuve et le degre d'accord des experts pour chacune des recommandations. Resultats : 1. Les cinq questions choisies portaient sur les modalites d'utilisation du MTX au cours de la PR : doses initiales et maximales, voie d'administration, posologie en cas d'association aux anti-TNFa, place de la supplementation en folates et examens complementaires necessaires a l'initiation et au suivi du traitement. 2. La recherche bibliographique a permis d'identifier 1859 citations, dont 285 articles ont ete extraits et retenus. L'analyse de la litterature a permis d'apporter des elements de reponses de type EBM qui ont ete presentes aux experts au cours d'ateliers interactifs. 3. Huit recommandations, dont le niveau de force varie de A a D, ont ete elaborees a l'issue de ces ateliers, puis validees par un vote final de l'ensemble des participants. Conclusion : des recommandations sur l'utilisation du MTX dans la PR ont ete developpees et devraient faciliter une plus grande homogeneite des pratiques cliniques et a terme une optimisation de la prise en charge de la PR.

Rheumatoid Arthritis and Fibromyalgia. Reply

Journal of Rheumatology, 2009

Risque cardiovasculaire et polyarthrite rhumatoïde : établissement de recommandations pour la pratique clinique à partir de données de la littérature et d'opinions d'experts

Revue Du Rhumatisme, 2005

Objectif : proposer des recommandations quant a l'evaluation et la prise en charge du risque ... more Objectif : proposer des recommandations quant a l'evaluation et la prise en charge du risque cardiovasculaire de la polyarthrite rhumatoide (PR) en pratique quotidienne, selon la methodologie de la medecine fondee sur les preuves (evidence based medicine - EBM) et l'opinion d'experts. Methodes : elaboration de recommandations en suivant une double approche fondee sur les preuves et sur l'avis d'experts. 1. Determination de cinq questions, base de la redaction des recommandations, par un comite scientifique selon la methode Delphi. 2. Recherche d'elements de reponse type EBM par une revue de la litterature. 3. Developpement de recommandations par un comite d'experts a partir de ces elements. Resultats : 1. Les cinq questions selectionnees portaient sur l'evaluation du risque cardiovasculaire dans la PR, sur les facteurs de risque rencontres dans la PR, l'influence des traitements de fond et les mesures therapeutiques. 2. La revue de la litterature a permis de selectionner 293 articles sur le titre et le resume. Les publications dont l'analyse ne concernait pas le risque cardiovasculaire dans la PR ont ete eliminees. Au final, 74 articles originaux ont ete inclus dans l'analyse globale. 3. Neuf recommandations relatives au risque cardiovasculaire de la PR ont ete elaborees a partir des resultats de la revue de la litterature et de l'opinion d'experts. Ces recommandations ont ete validees par un vote final de l'ensemble des participants. Conclusion : des recommandations relatives a l'evaluation et la prise en charge du risque cardiovasculaire de la PR ont ete developpees. Elles apportent un element objectif et consensuel de reponse a des questions cliniques pour la pratique clinique quotidienne.