Publications by authors named "Fabienne Coury"

26 Publications

  • Page 1 of 1

Rheumatoid Arthritis in the View of Osteoimmunology.

Biomolecules 2020 Dec 31;11(1). Epub 2020 Dec 31.

INSERM UMR1033 LYOS, University of Lyon I, 69003 Lyon, France.

Rheumatoid arthritis is characterized by synovial inflammation and irreversible bone erosions, both highlighting the immense reciprocal relationship between the immune and bone systems, designed osteoimmunology two decades ago. Osteoclast-mediated resorption at the interface between synovium and bone is responsible for the articular bone erosions. The main triggers of this local bone resorption are autoantibodies directed against citrullinated proteins, as well as pro-inflammatory cytokines and the receptor activator of nuclear factor-κB ligand, that regulate both the formation and activity of the osteoclast, as well as immune cell functions. In addition, local bone loss is due to the suppression of osteoblast-mediated bone formation and repair by inflammatory cytokines. Similarly, inflammation affects systemic bone remodeling in rheumatoid arthritis with the net increase in bone resorption, leading to systemic osteoporosis. This review summarizes the substantial progress that has been made in understanding the pathophysiology of systemic and local bone loss in rheumatoid arthritis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/biom11010048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823493PMC
December 2020

Increased high molecular weight adiponectin and lean mass during tocilizumab treatment in patients with rheumatoid arthritis: a 12-month multicentre study.

Arthritis Res Ther 2020 09 29;22(1):224. Epub 2020 Sep 29.

Laboratoire de Biochimie Médicale, UF de Biochimie Endocrinienne et Métabolique, CHU de Besançon; EA 3920 Marqueurs pronostiques et facteurs de régulation des pathologies cardiaques et vasculaires, Université de Bourgogne Franche Comté, Besançon, France.

Background: Patients with rheumatoid arthritis (RA) have an increased risk of cardiovascular (CV) disease. Adiponectin is involved in the metabolism of glucose and lipids with favourable effects on CV disease, especially its high molecular weight (HMW) isoform. Body composition changes are described in RA with various phenotypes including obesity. The effects of tocilizumab on serum adiponectin and body composition, especially fat mass, in patients with RA are not well determined.

Methods: Patients with active RA despite previous csDMARDs and/or bDMARDs and who were tocilizumab naïve were enrolled in a multicentre open-label study. They were evaluated at baseline, 1, 3, 6 and 12 months. Clinical assessment included body mass index (BMI) and anthropometric measurements. Lipid and metabolic parameters, serum adiponectin (total and HMW), leptin, resistin and ghrelin were measured at each time point. Body composition (lean mass, fat mass, % fat, fat in the android and gynoid regions) was evaluated at baseline, 6 and 12 months.

Results: One hundred seven patients were included. Both total and HMW adiponectin significantly increased from baseline to month 3, peaking respectively at month 3 (p = 0.0105) and month 1 (p < 0.0001), then declining progressively until month 6 to 12 and returning to baseline values. Significant elevation in HMW adiponectin persisted at month 6 (p = 0.001). BMI and waist circumference significantly increased at month 6 and 12, as well as lean mass at month 6 (p = 0.0097). Fat mass, percentage fat and android fat did not change over the study period. Lipid parameters (total cholesterol and LDL cholesterol) increased while glycaemia, insulin and HOMA-IR remained stable. Serum leptin, resistin and ghrelin did not change during follow-up.

Conclusions: Tocilizumab treatment in RA patients was associated with a significant increase in total and HMW adiponectin, especially at the onset of the treatment. Tocilizumab also induced a significant gain in lean mass, while fat mass did not change. These variations in adiponectin levels during tocilizumab treatment could have positive effects on the CV risk of RA patients. In addition, tocilizumab may have an anabolic impact on lean mass/skeletal muscle.

Trial Registration: The ADIPRAT study was a phase IV open-label multicentre study retrospectively registered on ClinicalTrials.gov under the number NCT02843789 (date of registration: July 26, 2016).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13075-020-02297-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7523335PMC
September 2020

Comparison of paediatric and adult classification criteria in juvenile idiopathic arthritis during the transition from paediatric to adult care.

Joint Bone Spine 2021 01 9;88(1):105047. Epub 2020 Jul 9.

Department of Rheumatology, Lyon University Hospital and University of Lyon 1, Lyon, France. Electronic address:

Objectives: To determine the characteristics of juvenile idiopathic arthritis (JIA) patients seen during the transition period in order to compare paediatric classification criteria with those for adults.

Methods: Patients with JIA according to the ILAR classification and who had a consultation at transition between 2010 and 2017 were included in a retrospective bi-centre (Lyon, Lausanne) study. JIA classification criteria were compared to ACR/EULAR 2010 criteria for rheumatoid arthritis (RA), Yamaguchi criteria for adult-onset Still's disease (AOSD), ASAS criteria for spondyloarthritis and CASPAR criteria for psoriatic arthritis.

Results: One hundred and thirty patients were included: 13.9% with systemic JIA, 22.3% with polyarticular JIA, 22.3% with oligoarticular JIA, 34.6% with enthesitis-related arthritis (ERA) and 6.9% with psoriatic arthritis; 13.1% had suffered from uveitis; 14.5% of patients had erosions or carpitis, mainly those with psoriatic arthritis, polyarticular or systemic JIA; 37.5% of patients with ERA displayed radiological sacroiliitis. When comparing paediatric JIA criteria with adult classifications, we found that: 66.6% of patients with systemic JIA fulfilled the criteria for AOSD, 87.5% of rheumatoid factor-positive polyarticular JIA and 9.5% of rheumatoid factor-negative polyarticular JIA met the criteria for RA, and 34.5% of oligoarticular JIA fulfilled the criteria for spondyloarthritis. Finally, 77.7% of patients with ERA met the criteria for spondyloarthritis, and 100% of patients with psoriatic arthritis JIA met the criteria for psoriatic arthritis.

Conclusion: Oligoarticular JIA and rheumatoid factor-negative polyarticular JIA seem to be paediatric entities, whereas the other types of JIA tended to meet the respective adult classification criteria.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jbspin.2020.06.020DOI Listing
January 2021

Infliximab induces clinical resolution of sacroiliitis that coincides with increased circulating FOXP3 T cells in a patient with IPEX syndrome.

Joint Bone Spine 2020 Oct 11;87(5):483-486. Epub 2020 May 11.

University Claude-Bernard Lyon 1, 69007 Lyon, France; Department of rheumatology, Lyon Sud hospital, hospices civils de Lyon, Pierre-Bénite, France; Inserm UMR1033, Lyon, France. Electronic address:

Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a rare monogenic primary immunodeficiency due to mutations of FOXP3, a master transcription factor of regulatory T cells (Treg). IPEX syndrome leads to fatal course in most cases during early childhood or severe multi-organ immune-mediated disorders in patients who survive. Currently hematopoietic stem cell transplantation represents the only known effective cure for IPEX syndrome. However, older patients with a mild disease not severe enough to justify transplantation, raise concerns regarding the appropriate therapeutic management, which is therefore based on supportive and replacement therapies combined with pharmacological immunosuppression. Herein, we report the case of a 22-year-old man with an incomplete IPEX syndrome without endocrine disorders having suffered from severe enteropathy since his birth treated with a combination of various immunosuppressant agents. He developed severe exacerbation of inflammatory low back pain in relation to sacroiliitis. Eventually, infliximab was initiated to control his back pain with rapid resolution as well as digestive improvement and also reduced biological inflammatory markers. In parallel, flow cytometry analysis revealed an increase in the frequency of circulating FOXP3+ CD4+ Treg cells. Altogether these data highlight that anti-TNF may represent a promising therapeutic option in patients with IPEX syndrome.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jbspin.2020.04.013DOI Listing
October 2020

Methotrexate Restores CD73 Expression on Th1.17 in Rheumatoid Arthritis and Psoriatic Arthritis Patients and May Contribute to Its Anti-Inflammatory Effect through Ado Production.

J Clin Med 2019 Nov 3;8(11). Epub 2019 Nov 3.

Immunology Department, University of Lyon, Claude Bernard Lyon 1 University, INSERM 1052, CNRS 5286, Cancer Research Center of Lyon (CRCL), Centre Léon Bérard, 69008 Lyon, France.

Objectives: Th1.17 are highly polyfunctional, potentially harmful CD4 effector T cells (Teff) through IFN-γ and IL-17A coproduction. Th1.17 take part in the pathophysiology of rheumatoid arthritis (RA) and psoriatic arthritis (PsA), in which their hyper activation results in part from defects in negative regulation mechanisms. We recently demonstrated that the ecto-nucleotidase CD73 delineates a Th1.17-enriched Teff population and acts as an endogenous regulatory mechanism. Because Methotrexate (MTX), used as first line treatment of RA and PsA, increases extracellular concentrations of AMP and immunosuppressive adenosine, we investigated the modulation of CD73 by MTX treatment on Teff in RA/PsA patients.

Methods: In a prospective cohort of 26 RA and 15 PsA patients before or under MTX treatment, we evaluated CD73 expression on blood Teff subsets, their cytokine production and AMPase functions.

Results: We showed a decreased CD73 expression on Th1.17 and Th1 in untreated patients compared to healthy donors that was partly restored under MTX. This decrease in untreated patients leads to a halved Ado production by Th1.17 cells. CD73 Teff remained functional under MTX treatment, but their CD73 re-expression may contribute to control their activation.

Conclusion: Our study unveils uncovered mode of action of MTX on Teff subsets modulation and in the adenosine-dependent termination of inflammation in RA and PsA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/jcm8111859DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6912794PMC
November 2019

Osteoclast-Derived Autotaxin, a Distinguishing Factor for Inflammatory Bone Loss.

Arthritis Rheumatol 2019 11 30;71(11):1801-1811. Epub 2019 Sep 30.

INSERM UMR 1033 LYOS and University of Lyon I, Lyon, France, and Lyon Sud Hospital, Pierre-Bénite, France.

Objective: The severity of rheumatoid arthritis (RA) correlates directly with bone erosions arising from osteoclast (OC) hyperactivity. Despite the fact that inflammation may be controlled in patients with RA, those in a state of sustained clinical remission or low disease activity may continue to accrue erosions, which supports the need for treatments that would be suitable for long-lasting inhibition of OC activity without altering the physiologic function of OCs in bone remodeling. Autotaxin (ATX) contributes to inflammation, but its role in bone erosion is unknown.

Methods: ATX was targeted by inhibitory treatment with pharmacologic drugs and also by conditional inactivation of the ATX gene Ennp2 in murine OCs (ΔATX ). Arthritic and erosive diseases were studied in human tumor necrosis factor-transgenic (hTNF ) mice and mice with K/BxN serum transfer-induced arthritis. Systemic bone loss was also analyzed in mice with lipopolysaccharide (LPS)-induced inflammation and estrogen deprivation. Joint inflammation and bone erosion were assessed by histology and micro-computed tomography. The role of ATX in RA was also examined in OC differentiation and activity assays.

Results: OCs present at sites of inflammation overexpressed ATX. Pharmacologic inhibition of ATX in hTNF mice, as compared to vehicle-treated controls, significantly mitigated focal bone erosion (36% decrease; P < 0.05) and systemic bone loss (43% decrease; P < 0.05), without affecting synovial inflammation. OC-derived ATX was revealed to be instrumental in OC bone resorptive activity and was up-regulated by the inflammation elicited in the presence of TNF or LPS. Specific loss of ATX in OCs from mice subjected to ovariectomy significantly protected against the systemic bone loss and erosion that had been induced with LPS and K/BxN serum treatments (30% reversal of systemic bone loss [P < 0.01]; 55% reversal of erosion [P < 0.001]), without conferring bone-protective properties.

Conclusion: Our results identify ATX as a novel OC factor that specifically controls inflammation-induced bone erosions and systemic bone loss. Therefore, ATX inhibition offers a novel therapeutic approach for potentially preventing bone erosion in patients with RA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/art.41005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6817375PMC
November 2019

Osteoimmunology of Bone Loss in Inflammatory Rheumatic Diseases.

Front Immunol 2019 3;10:679. Epub 2019 Apr 3.

INSERM, UMR1033 LYOS, Lyon, France.

Over the past two decades, the field of osteoimmunology has emerged in response to a range of evidence demonstrating the reciprocal relationship between the immune system and bone. In particular, localized bone loss, in the form of joint erosions and periarticular osteopenia, as well as systemic osteoporosis, caused by inflammatory rheumatic diseases including rheumatoid arthritis, the prototype of inflammatory arthritis has highlighted the importance of this interplay. Osteoclast-mediated resorption at the interface between synovium and bone is responsible for the joint erosion seen in patients suffering from inflammatory arthritis. Clinical studies have helped to validate the impact of several pathways on osteoclast formation and activity. Essentially, the expression of pro-inflammatory cytokines as well as Receptor Activator of Nuclear factor κB Ligand (RANKL) is, both directly and indirectly, increased by T cells, stimulating osteoclastogenesis and resorption through a crucial regulator of immunity, the Nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1). Furthermore, in rheumatoid arthritis, autoantibodies, which are accurate predictors both of the disease and associated structural damage, have been shown to stimulate the differentiation of osteoclasts, resulting in localized bone resorption. It is now also evident that osteoblast-mediated bone formation is impaired by inflammation both in joints and the skeleton in rheumatoid arthritis. This review summarizes the substantial progress that has been made in understanding the pathophysiology of bone loss in inflammatory rheumatic disease and highlights therapeutic targets potentially important for the cure or at least an alleviation of this destructive process.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fimmu.2019.00679DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6456657PMC
July 2020

Teriparatide treatment in an adult patient with hypophosphatasia exposed to bisphosphonate and revealed by bilateral atypical fractures.

Joint Bone Spine 2018 05 12;85(3):365-367. Epub 2017 Dec 12.

Service de rhumatologie, centre hospitalier Lyon Sud, 165, chemin du Grand-Revoyet, 69495 Pierre-Bénite, France; Université de Lyon I, 69007 Lyon, France.

Atypical femoral fractures are defined as atraumatic fractures located in the subtrochanteric region or femoral shaft. They have been mainly reported in patients taking bisphosphonates. We report the case of a 67-year-old female with osteoporosis treated by alendronate during ten years. Radiographies showed atypical femoral fractures. Serum levels of total and bone-specific alkaline phosphatase were low. In order to accelerate bone healing, teriparatide was introduced. After one year of teriparatide treatment, pain and functional difficulty have decreased, and alkaline phosphatase levels were normalized. In view of this history of recurrent fractures, of atypical femoral fractures, of early spontaneous loss of teeth, and of low serum total and bone-specific alkaline phosphatase levels, the diagnosis of hypophosphatasia has been considered and confirmed by genetic research. Other conditions than exposure to anti-resorptive therapies may promote atypical femoral fractures, such as in conditions associated with abnormal bone structures, as hypophosphatasia, a rare inherited bone metabolism disorder. A few case reports have reported adult hypophosphatasia treated by teriparatide with a good efficacy on bone pain and consolidation but with mixed results on biological markers. Teriparatide may be therefore a treatment option in adult hypophosphatasia. ALP levels should be carefully checked among osteoporotic patients and specially before introducing a bone resorption inhibitor. Low alkaline phosphatase levels have to be taken into account and an evocative history of hypophosphatasia has to be sought because this condition may expose patients to develop atypical femoral fractures during bisphosphonate treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jbspin.2017.12.001DOI Listing
May 2018

Genetic analysis of adults heterozygous for ALPL mutations.

J Bone Miner Metab 2018 Nov 13;36(6):723-733. Epub 2017 Dec 13.

Unité de Génétique Constitutionnelle, Service de Biologie, Centre Hospitalier de Versailles, 177 rue de Versailles, 78150, Le Chesnay, France.

Hypophosphatasia (HPP) is a rare inherited metabolic bone disease due to a deficiency of the tissue nonspecific alkaline phosphatase isoenzyme (TNSALP) encoded by the ALPL gene. Patients have consistently low serum alkaline phosphatase (AP), so that this parameter is a good hallmark of the disease. Adult HPP is heterogeneous, and some patients present only mild nonpathognomonic symptoms which are also common in the general population such as joint pain, osteomalacia and osteopenia, chondrocalcinosis, arthropathy and musculoskeletal pain. Adult HPP may be recessively or dominantly inherited; the latter case is assumed to be due to the dominant negative effect (DNE) of missense mutations derived from the functional homodimeric structure of TNSALP. However, there is no biological argument excluding the possibility of other causes of dominant HPP. Rheumatologists and endocrinologists are increasingly solicited for patients with low AP and nonpathognomonic symptoms of HPP. Many of these patients are heterozygous for an ALPL mutation and a challenging question is to determine if these symptoms, which are also common in the general population, are attributable to their heterozygous ALPL mutation or not. In an attempt to address this question, we reviewed a cohort of 61 adult patients heterozygous for an ALPL mutation. Mutations were distinguished according to their statistical likelihood to show a DNE. One-half of the patients carried mutations predicted with no DNE and were slightly less severely affected by the age of onset, serum AP activity and history of fractures. We hypothesized that these mutations result in another mechanism of dominance or are recessive alleles. To identify other genetic factors that could trigger the disease phenotype in heterozygotes for potential recessive mutations, we examined the next-generation sequencing results of 32 of these patients for a panel of 12 genes involved in the differential diagnosis of HPP or candidate modifier genes of HPP. The heterozygous genotype G/C of the COL1A2 coding SNP rs42524 c.1645C > G (p.Pro549Ala) was associated with the severity of the phenotype in patients carrying mutations with a DNE whereas the homozygous genotype G/G was over-represented in patients carrying mutations without a DNE, suggesting a possible role of this variant in the disease phenotype. These preliminary results support COL1A2 as a modifier gene of HPP and suggest that a significant proportion of adult heterozygotes for ALPL mutations may have unspecific symptoms not attributable to their heterozygosity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00774-017-0888-6DOI Listing
November 2018

Antimalarial drug retinopathy: A typical « Bull's eyes » appearance of fundus.

Joint Bone Spine 2018 05 13;85(3):369. Epub 2017 May 13.

Département de Rhumatologie, hospices civils de Lyon, centre hospitalier Lyon Sud, 69495 Pierre-Bénite, France; Université Lyon 1, 69000 Lyon, France.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jbspin.2017.05.007DOI Listing
May 2018

Tumor Necrosis Factor Alpha Overexpression Induces Mainly Osteoclastogenesis at the Vertebral Site.

Calcif Tissue Int 2017 06 13;100(6):575-584. Epub 2017 Mar 13.

INSERM, UMR1033, University Claude Bernard Lyon 1, UFR de Médecine Lyon Est, Rue Guillaume Paradin, 69372, Lyon Cedex 08, France.

Syndesmophyte occurrence and axial bone loss were investigated in the heterozygous Tg187 tumor necrosis factor (TNF) transgenic mouse model (Tg-huTNF) of arthritis. Female and male Tg-huTNF mice were compared to wild-type mice (WT) at 2, 4, 6, 8, and 10 weeks. Syndesmophytes, intervertebral disc space, osteoclasts, osteoid surface, and vertebra microarchitecture were assessed by histomorphometry and microcomputed tomography. No spontaneous syndesmophyte formation was detected in Tg-huTNF compared to WT mice. However, increased porosity was observed mainly in peridiscal lumbar vertebra. Accordingly, bone microarchitecture parameters were altered in Tg-huTNF mice, with decrease in bone volume fraction, and trabecular number and thickness after 6 weeks compared to WT (p < 0.05). Osteoclast count and surface were increased (p < 0.01). Moreover, the non-mineralized (osteoid) surface was also increased in Tg-huTNF after 6 weeks (p < 0.01). Despite increased osteoclast and osteoid surfaces, an imbalance between both was observed in favour of osteoid surface at the early phase and then to osteoclast surface. These results demonstrated an axial bone loss in the Tg-huTNF model, additional to the common limb arthritis, related to overexpression of TNF. However, the absence of syndesmophyte and the increase of osteoid surface suggested that chronic inflammation might block bone mineralisation. Finally, the relative increased osteoid surface was not enough to compensate the high osteoclast activity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00223-017-0237-8DOI Listing
June 2017

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

Joint Bone Spine 2018 03 24;85(2):201-205. Epub 2017 Feb 24.

Département de rhumatologie, hospices civils de Lyon, centre hospitalier Lyon Sud, 69495 Pierre-Bénite, France; Université Lyon 1, Lyon, France. Electronic address:

Objective: 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.

Methods: 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.

Results: Twenty-seven patients were included between 2002 and 2012 compared with 31 between 1986 and 1996. The overall incidence of ReA in patients hospitalised in the rheumatology department did not change, although the current evolution is more severe with development of chronic disease in the form of more frequent spondyloarthritis. While the incidence of Chlamydiae trachomatis has decreased, new microbes are now found to be involved.

Conclusions: ReA still exists and its incidence has been stable over the last 30 years. However, ReA currently more often progress to spondyloarthritis. Our study also highlights the need for diagnostic criteria that accurately detect ReA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jbspin.2017.01.013DOI Listing
March 2018

Posterior epidural migration of herniated lumbar disc fragment.

Joint Bone Spine 2017 10 29;84(5):623. Epub 2016 Dec 29.

Service de rhumatologie, Centre Hospitalier Lyon-Sud, Hospices civils de Lyon, 165 Chemin du Grand Revoyet, 69310 Pierre-Bénite, France; Université Lyon 1, 69000 Lyon, France.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jbspin.2016.12.005DOI Listing
October 2017

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

J Rheumatol 2016 11 15;43(11):2056-2063. Epub 2016 Sep 15.

From the Service de Rhumatologie, Centre Hospitalier Lyon-Sud, Pierre-Bènite, France.

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 Short Form-36 questionnaire were recorded and compared.

Results: The study included 103 patients with SpA; 81 with axial and 22 with peripheral forms. Eighteen patients presented with concomitant FM, of whom 12 had axial SpA and 6 peripheral SpA. Demographic characteristics did not differ except for sex, with a female predominance in the FM group that was more marked in peripheral forms. BASDAI was higher in patients with FM [median (IQR): 4.2 (4.2) vs 2.2 (3.1); p = 0.0068], whereas ASDAS-CRP was not significantly different [median (IQR): 2.7 (2) vs 2 (1.3); p = 0.1264]. Nevertheless, median ASDAS-CRP corresponded to high disease activity in patients with SpA or FM compared with moderate activity in non-FM patients.

Conclusion: FM is a frequent comorbidity in patients with SpA, especially in peripheral forms. In patients with SpA-FM, disease activity may be overestimated when measured by BASDAI and to a lesser extent by ASDAS-CRP, and this overestimation could lead to inappropriate treatment escalation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3899/jrheum.160104DOI Listing
November 2016

Early treatment of reactive arthritis with etanercept and 2 years follow-up.

Joint Bone Spine 2017 05 3;84(3):367. Epub 2016 Jun 3.

Service de rhumatologie, centre hospitalier Lyon Sud, 69310 Pierre-Bénite, France; Université Claude-Bernard Lyon, 69622 Villeurbanne cedex, France.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jbspin.2016.05.002DOI Listing
May 2017

Antisynthetase syndrome treated with tocilizumab.

Joint Bone Spine 2016 May 23;83(3):361-2. Epub 2015 Oct 23.

Department of Rheumatology, centre hospitalier Lyon Sud, 165, chemin du Grand-Revoyet, 69495 Pierre-Bénite, France; University of Lyon I, 69007 Lyon, France.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jbspin.2015.03.016DOI Listing
May 2016

Spinal cord compression revealing a lambda light chain multiple myeloma.

Joint Bone Spine 2013 Oct 24;80(5):538. Epub 2013 Sep 24.

Service de rhumatologie, centre hospitalier Lyon-Sud, 165, chemin du Grand-Revoyet, 69495 Pierre-Bénite cedex, France. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jbspin.2013.07.010DOI Listing
October 2013

SLC4A2-mediated Cl-/HCO3- exchange activity is essential for calpain-dependent regulation of the actin cytoskeleton in osteoclasts.

Proc Natl Acad Sci U S A 2013 Feb 22;110(6):2163-8. Epub 2013 Jan 22.

Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA.

Bone remodeling requires osteoclasts to generate and maintain an acidified resorption compartment between the apical membrane and the bone surface to solubilize hydroxyapatite crystals within the bone matrix. This acidification process requires (i) apical proton secretion by a vacuolar H(+)-ATPase, (ii) actin cytoskeleton reorganization into a podosome belt that forms a gasket to restrict lacunar acid leakage, and (iii) basolateral chloride uptake and bicarbonate extrusion by an anion exchanger to provide Cl(-) permissive for apical acid secretion while preventing cytoplasmic alkalinization. Here we show that osteoclast-targeted deletion in mice of solute carrier family 4 anion exchanger member 2 (Slc4a2) results in osteopetrosis. We further demonstrate a previously unrecognized consequence of SLC4A2 loss of function in the osteoclast: dysregulation of calpain-dependent podosome disassembly, leading to abnormal actin belt formation, cell spreading, and migration. Rescue of SLC4A2-deficient osteoclasts with functionally defined mutants of SLC4A2 indicates regulation of actin cytoskeletal reorganization by anion-exchange activity and intracellular pH, independent of SLC4A2's long N-terminal cytoplasmic domain. These data suggest that maintenance of intracellular pH in osteoclasts through anion exchange regulates the actin superstructures required for bone resorption.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1073/pnas.1206392110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3568349PMC
February 2013

The collection of NFATc1-dependent transcripts in the osteoclast includes numerous genes non-essential to physiologic bone resorption.

Bone 2012 Nov 16;51(5):902-12. Epub 2012 Aug 16.

Department of Medicine, Division of Rheumatology, Allergy and Immunology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.

Osteoclasts are specialized secretory cells of the myeloid lineage important for normal skeletal homeostasis as well as pathologic conditions of bone including osteoporosis, inflammatory arthritis and cancer metastasis. Differentiation of these multinucleated giant cells from precursors is controlled by the cytokine RANKL, which through its receptor RANK initiates a signaling cascade culminating in the activation of transcriptional regulators which induce the expression of the bone degradation machinery. The transcription factor nuclear factor of activated T-cells c1 (NFATc1) is the master regulator of this process and in its absence osteoclast differentiation is aborted both in vitro and in vivo. Differential mRNA expression analysis by microarray is used to identify genes of potential physiologic relevance across nearly all biologic systems. We compared the gene expression profile of murine wild-type and NFATc1-deficient osteoclast precursors stimulated with RANKL and identified that the majority of the known genes important for osteoclastic bone resorption require NFATc1 for induction. Here, five novel RANKL-induced, NFATc1-dependent transcripts in the osteoclast are described: Nhedc2, Rhoc, Serpind1, Adcy3 and Rab38. Despite reasonable hypotheses for the importance of these molecules in the bone resorption pathway and their dramatic induction during differentiation, the analysis of mice with mutations in these genes failed to reveal a function in osteoclast biology. Compared to littermate controls, none of these mutants demonstrated a skeletal phenotype in vivo or alterations in osteoclast differentiation or function in vitro. These data highlight the need for rigorous validation studies to complement expression profiling results before functional importance can be assigned to highly regulated genes in any biologic process.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bone.2012.08.113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3457000PMC
November 2012

Rheumatoid arthritis and fibromyalgia: a frequent unrelated association complicating disease management.

J Rheumatol 2009 Jan;36(1):58-62

Service de Rhumatologie, Centre Hospitalier Lyon Sud, and UFR Sciences, Université Lyon I, Lyon, France.

Objective: To assess the value of the 28-joint Disease Activity Score (DAS28) in evaluating disease activity in rheumatoid arthritis (RA) associated with fibromyalgia (FM). In this situation, because of the weight of the subjective measures included in the DAS28 equation, the patient's status may be overestimated, leading to inappropriate treatment. We analyze the relationship between RA and FM and discuss whether the association is random or a marker of poor prognosis.

Methods: A questionnaire, developed when biologic therapies were introduced, was administered and the results analyzed in a consecutive, female outpatient population including 105 patients with RA, 49 with RA and FM (RAF), and 28 with FM. Psychosocial characteristics, disease presentation, and radiographic joint destruction evaluation were compared in the 3 populations.

Results: The presentation of RA was the same in patients with RA and RAF, but the 2 populations differed by socioprofessional characteristics, significantly higher disease activity in patients with RAF, and significantly more severe joint destruction in patients with RA. The RAF group was similar to the FM control population in socioprofessional and some physical characteristics. Regression analysis using the DAS28 measures differed significantly in the weight allowed to 28-joint counts for pain and swelling, but the constant factor was higher in patients with RAF.

Conclusion: DAS28 overestimated objective RA severity in patients who also had FM. The association between RA and FM does not appear to be a marker of worse prognosis, but rather a fortuitous association between the 2 diseases and one that may afford these patients some protection against joint destruction.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3899/jrheum.080366DOI Listing
January 2009

Safety, efficacy and predictive factors of efficacy of a single intra-articular injection of non-animal-stabilized-hyaluronic-acid in the hip joint: results of a standardized follow-up of patients treated for hip osteoarthritis in daily practice.

Arch Orthop Trauma Surg 2009 Jun 15;129(6):843-8. Epub 2008 Nov 15.

Department of Rheumatology (Pr VIGNON), University Hospital Lyon-Sud, Pierre Benite Cedex, France.

Aim: To evaluate, in daily clinical practice, the efficacy and tolerability of a single intra-articular injection of non-animal-stabilized hyaluronic acid (NASHA) in patients treated for symptomatic hip OA (HOA).

Methods: Standardized follow-up (FU).

Patients: forty patients suffering from HOA treated by a single intra-articular injection of NASHA in the painful hip under fluoroscopy.

Evaluation: patient global assessment (PGA) and walking pain (WP) on a 100 mm visual analogue scale, WOMAC index, Lequesne index at each visit.

Statistics: last observation carried forward. Treatment efficacy was assessed using OMERACT-OARSI response criteria, minimal clinically important improvement (MCII), patient acceptable symptom state (PASS) obtained from PGA, WOMAC and WP. Predictive factors of efficacy were also studied.

Results: Efficacy evaluation: 34 patients were assessable (mean FU 159 days). All clinical variables (WP, PGA, WOMAC, Lequesne index) decreased significantly between baseline and last evaluation. Twenty-two patients (71%) were classified OMERACT-OARSI responders, 25 subjects (75.8%) were classified PASS+, and 19 (61.3%) fulfilled criteria for MCII. Out of clinical and radiological variables only Lequesne index (p = 0.04) and WOMAC (p = 0.04) at baseline were found to be predictive of treatment efficacy. Safety evaluation: the treatment was well tolerated. There were no severe adverse events related to the treatment or to the procedure. However 15 of the 28 assessable patients experienced transient increase of pain in the target hip during the first week after injection.

Conclusion: Viscosupplementation of the hip with NASHA is easily feasible in daily clinical practice, safe and well tolerated despite a frequent increase of pain the days following injection. Prospective controlled trials are needed to confirm these data and to evaluate both safety and efficacy of a second course of treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00402-008-0778-4DOI Listing
June 2009

Langerhans cell histiocytosis reveals a new IL-17A-dependent pathway of dendritic cell fusion.

Nat Med 2008 Jan 23;14(1):81-7. Epub 2007 Dec 23.

INSERM, U851, 21 Avenue Tony Garnier, Lyon 5-69007, France.

IL-17A is a T cell-specific cytokine that is involved in chronic inflammations, such as Mycobacterium infection, Crohn's disease, rheumatoid arthritis and multiple sclerosis. Mouse models have explained the molecular basis of IL-17A production and have shown that IL-17A has a positive effect not only on granuloma formation and neurodegeneration through unknown mechanisms, but also on bone resorption through Receptor activator of NF-kappaB ligand (RANKL) induction in osteoblasts. Langerhans cell histiocytosis (LCH) is a rare disease of unknown etiology, lacking an animal model, that cumulates symptoms that are found separately in various IL-17A-related diseases, such as aggressive chronic granuloma formation, bone resorption and soft tissue lesions with occasional neurodegeneration. We examined IL-17A in the context of LCH and found that there were high serum levels of IL-17A during active LCH and unexpected IL-17A synthesis by dendritic cells (DCs), the major cell type in LCH lesions. We also found an IL-17A-dependent pathway for DC fusion, which was highly potentiated by IFN-gamma and led to giant cells expressing three major tissue-destructive enzymes: tartrate resistant acidic phosphatase and matrix metalloproteinases 9 and 12. IFN-gamma expression has been previously documented in LCH and observed in IL-17A-related diseases. Notably, serum IL-17A-dependent fusion activity correlates with LCH activity. Thus, IL-17A and IL-17A-stimulated DCs represent targets that may have clinical value in the treatment of LCH and other IL-17A-related inflammatory disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/nm1694DOI Listing
January 2008

Murine dendritic cell transdifferentiation into osteoclasts is differentially regulated by innate and adaptive cytokines.

Eur J Immunol 2007 Mar;37(3):747-57

INSERM, U503, Université de Lyon, Université Lyon 1, IFR128, Lyon, France.

Dendritic cells (DC) are the mononuclear cells that initiate adaptive immune responses. Osteoclasts (OC) are the multinucleated giant cells that resorb bone. As previously described for human conventional DC (cDC), we demonstrate that murine cDC, either in vitro generated from Fms-like tyrosine kinase 3 (Flt3)+ bone marrow progenitors or ex vivo purified from spleen, are able to develop into OC in response to M-CSF and receptor activator of NF-kappaB ligand (RANKL) in vitro. This transdifferentiation is driven by the immune environment that controls cDC maturation, cell fusion, tartrate-resistant acid phosphatase (TRAP) and bone resorption activities. Only immature cDC have the capacity to become OC since mature cDC or plasmacytoid DC do not. Additions of the pro-inflammatory cytokines, such as IL-1beta and TNF-alpha, or human rheumatoid synovial fluid, increase murine cDC transdifferentiation into OC, whereas IFN-alpha inhibits it. The adaptive cytokine, IFN-gamma, inhibits cDC fusion while IL-4 increases it. IL-2, IFN-gamma and IL-4 inhibit TRAP and bone resorption activities contrary to IL-10, which enhances both activities. A putative new "immune multinucleated giant cell" unable to resorb bone, which is formed owing to IL-4, is underlined. The future analysis of cDC transdifferentiation into OC in murine models of inflammatory arthritis will give us the quantitative importance of this phenomenon in vivo.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/eji.200636534DOI Listing
March 2007

Infliximab therapy in rheumatoid arthritis and ankylosing spondylitis-induced specific antinuclear and antiphospholipid autoantibodies without autoimmune clinical manifestations: a two-year prospective study.

Arthritis Res Ther 2004 23;6(6):R535-43. Epub 2004 Sep 23.

UF Autoimmunité, Laboratoire d'Immunologie, Centre Hospitalier Lyon-Sud, Pierre Bénite, France.

Treatment of rheumatoid arthritis (RA) with infliximab (Remicade) has been associated with the induction of antinuclear autoantibodies (ANA) and anti-double-stranded DNA (anti-dsDNA) autoantibodies. In the present study we investigated the humoral immune response induced by infliximab against organ-specific or non-organ-specific antigens not only in RA patients but also in patients with ankylosing spondylitis (AS) during a two-year followup. The association between the presence of autoantibodies and clinical manifestations was then examined. The occurrence of the various autoantibodies was analyzed in 24 RA and 15 AS patients all treated with infliximab and in 30 RA patients receiving methotrexate but not infliximab, using the appropriate methods of detection. Infliximab led to a significant induction of ANA and anti-dsDNA autoantibodies in 86.7% and 57% of RA patients and in 85% and 31% of AS patients, respectively. The incidence of antiphospholipid (aPL) autoantibodies was significantly higher in both RA patients (21%) and AS patients (27%) than in the control group. Most anti-dsDNA and aPL autoantibodies were of IgM isotype and were not associated with infusion side effects, lupus-like manifestations or infectious disease. No other autoantibodies were shown to be induced by the treatment. Our results confirmed the occurrence of ANA and anti-dsDNA autoantibodies and demonstrated that the induction of ANA, anti-dsDNA and aPL autoantibodies is related to infliximab treatment in both RA and AS, with no significant relationship to clinical manifestations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/ar1440DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1064868PMC
November 2005