Nicole Fabien

Hospices Civils de Lyon, Lyons, Rhône-Alpes, France

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Publications (123)386.08 Total impact

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    ABSTRACT: Anti-signal recognition particle (SRP) antibodies are important serological markers for the diagnosis and the prognosis of idiopathic inflammatory myopathy (IIM), especially to distinguish immune-mediated necrotizing myopathy (IMNM). This study was set up to investigate the phenotype associated with anti-SRP antibodies and to evaluate the methods for detecting these antibodies. Clinical and biological data were retrospectively obtained from 60 adult patients with anti-SRP antibodies detected by a dot immunoassay from 12 centers. Thirty-six (60 %) out of these 60 patients suffered from an IIM, and among them, 21 patients were diagnosed as IMNM. Among patients with a definite IIM, proximal weakness and myalgia were prominent symptoms at the time of diagnosis. Only few patients displayed severe extra-muscular symptoms such as cardiac involvement or severe myositis. Mean creatine kinase levels were high for all patients except for two of them. When testing by indirect immunofluorescence (IIF) on HEp2 cells, the fraction of patients displaying the typical anti-SRP fine speckled staining of the cytoplasm was higher in patients with IIM (30/36) (83 %) than in patients with non-IIM (3/24) (12.5 %) (p < 0.0001). Thirty (91 %) out of 33 patients with a positive immunodot and a characteristic IIF cytoplasmic staining suffered from a clinical definite myositis, whereas only 6 (22 %) out of 27 patients with a positive immunodot but a negative cytoplasmic pattern suffered from a myositis (p < 0.00001). This series highlights the strong heterogeneity of anti-SRP positivity that encompassed IMNM and non-IMNM and supports the necessity of considering both IIF and dot immunoassay to confirm the diagnosis of anti-SRP-associated myositis.
    No preview · Article · Jan 2016 · Immunologic Research
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    ABSTRACT: La dermatomyosite juvénile (DMJ) est la plus fréquente des myopathies inflammatoires de l’enfant. Son diagnostic est essentiellement clinique et repose sur les critères de Bohan et Peter (1975). Plus récemment, des auto-anticorps spécifiques des myosites (MSA) ont pu être associés chez l’adulte à des formes évolutives particulières. Leur valeur diagnostique et pronostique reste à déterminer chez l’enfant. Nous rapportons 4 cas de DMJ avec MSA dont nous décrivons les caractéristiques cliniques, biologiques et radiologiques ainsi que les traitements utilisés. L’étude immunologique a montré la présence d’un anticorps (Ac) anti-MDA5 (ou CADM 140), un anti-TIF-1-γ (ou p155/140) et 2 anti-NXP2 (ou p140/MJ). Les 4 enfants avaient une atteinte cutanée typique ou sévère, en particulier celui ayant des Ac anti-TIF-1-gamma qui avait présenté des lésions initialement urticariformes avec un œdème important des paupières, puis des lésions de vascularite nécrotique au niveau du décolleté. Ils ont tous présenté une atteinte musculaire initiale sauf celui ayant des Ac anti-MDA 5 qui a eu une atteinte musculaire secondaire avec un taux de créatine-phosphokinase (CPK) normal, la particularité de son tableau étant marquée par une pancréatite aiguë grave. Ces nouveaux auto-Ac spécifiques pourraient devenir des outils diagnostiques et thérapeutiques mais également des paramètres pronostiques déterminants.
    No preview · Article · Nov 2015
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    ABSTRACT: Key Clinical Message Early diagnosis of potentially life-threatening autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is crucial, but is often delayed due to the clinical heterogeneity of the disorder. Even in the absence of the classic disease triad of chronic mucocutaneous candidiasis, hypoparathyroidism, and adrenocortical insufficiency, a diagnosis of APECED should be considered in children who have hypoparathyroidism and chronic keratitis, with a past medical history showing a mild and transient Candida infection.
    Full-text · Article · Aug 2015

  • No preview · Article · Jun 2015 · European Respiratory Review
  • C. Picard · N. Fabien · B. Ranchin · P. Cochat · A. Belot
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    ABSTRACT: Background Lupus nephritis (LN) frequently occurs in the clinical course of childhood-onset systemic lupus erythematosus (cSLE) and is involved in higher long-term morbidity and mortality of the disease compared to adults. Avoiding a progression to end-stage renal disease and, in the same time, minimizing current toxic treatment regimens is challenging in such young patients. Hence, clinicians need reliable biological markers in order to predict renal involvement. The association of anti-C1q antibodies (Abs) with lupus nephritis in adults is supported by several studies but remains uncertain in children. Objectives This single center study aimed at investigating the capacity of anti-C1q Abs to predict renal flare at diagnosis and during the follow-up of cSLE. Methods Anti-C1q Abs assays were performed retrospectively by ELISA in 17 patients from a single tertiary center, presenting with cSLE at diagnosis, at time of a renal flare-up or in a quiescent phase of the disease. Disease activity was measured with SLEDAI score which includes dsDNA aAbs. C3, C4, type I interferon were also analyzed in all patients. Results Five patients with a renal involvement at diagnosis of cSLE had positive anti-C1q aAbs at a high rate (>200UI/ml) (100%). A total of 11 flares were recorded during the time of the study. Anti-C1q antibodies were positive in 8 of these flares (72,7%). The negativity of anti-C1q Abs during these flares (n=3) was presumably due for one patient to a monogenic form of cSLE associated with a homozygous PRKCD mutation. In the other cases, levels of anti-C1q Abs were just below the limit of positivity and became positive at the time of the next renal flare. Conclusions Anti-C1q antibodies represent a reliable marker of LN flares in children with cSLE and may be performed routinely during the follow-up of these patients. References Disclosure of Interest None declared
    No preview · Article · Jun 2015 · Annals of the Rheumatic Diseases

  • No preview · Article · Jun 2015 · La Revue de Médecine Interne
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    ABSTRACT: Idiopathic inflammatory myositis (IIM) is a group of rare connective tissue diseases (CTDs) characterised by muscular and extramuscular signs, in which lung involvement is a challenging issue. Interstitial lung disease (ILD) is the hallmark of pulmonary involvement in IIM, and causes morbidity and mortality, resulting in an estimated excess mortality of 50% in some series. Except for inclusion body myositis, these extrapulmonary disorders are associated with the general and visceral involvement frequently found in other CTDs including fever, Raynaud's phenomenon, arthralgia, nonspecific cutaneous modifications and ILD, for which the prevalence is estimated to be up to 65%. Substantial heterogeneity exists within the spectrum of IIMs, and each condition is associated with various frequencies and subtypes of pulmonary involvement. This heterogeneity is partly related to the presence of various autoantibodies encompassing anti-synthetase, anti-MDA5 and anti-PM/Scl. ILD is present in all subsets of IIM including juvenile myositis, but is more frequent in dermatomyositis and overlap myositis. IIM can also be associated with other presentations of respiratory involvement, namely pulmonary arterial hypertension, pleural disease, infections, drug-induced toxicity, malignancy and respiratory muscle weakness. Here, we critically review the current knowledge about adult and juvenile myositis-associated lung disease with a detailed description of therapeutics for chronic and rapidly progressive ILD. Copyright ©ERS 2015.
    Full-text · Article · Jun 2015 · European Respiratory Review
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    ABSTRACT: We report here on the clinical, histological and immunological findings regarding a patient with immunodysregulation polyendocrinopathy enteropathy X-linked syndrome who was treated for the first 21years with a combination of immunosuppressant agents (IS). The potential modalities of care and treatment options in this rare and severe immune-mediated disorder are discussed. So, long-term outcome for IPEX patients can be obtained with immunosuppressive treatment, which is important since the outcome of haematopoietic stem cell transplantation for this population is variable. Copyright © 2015. Published by Elsevier Masson SAS.
    Full-text · Article · May 2015 · Gastroentérologie Clinique et Biologique

  • No preview · Poster · Apr 2015
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    ABSTRACT: PRKDC encodes for DNA-dependent protein kinase catalytic subunit (DNA-PKcs), a kinase that forms part of a complex (DNA-dependent protein kinase [DNA-PK]) crucial for DNA double-strand break repair and V(D)J recombination. In mice DNA-PK also interacts with the transcription factor autoimmune regulator (AIRE) to promote central T-cell tolerance. We sought to understand the causes of an inflammatory disease with granuloma and autoimmunity associated with decreasing T- and B-cell counts over time that had been diagnosed in 2 unrelated patients. Genetic, molecular, and functional analyses were performed to characterize an inflammatory disease evocative of a combined immunodeficiency. We identified PRKDC mutations in both patients. These patients exhibited a defect in DNA double-strand break repair and V(D)J recombination. Whole-blood mRNA analysis revealed a strong interferon signature. On activation, memory T cells displayed a skewed cytokine response typical of TH2 and TH1 but not TH17. Moreover, mutated DNA-PKcs did not promote AIRE-dependent transcription of peripheral tissue antigens in vitro. The latter defect correlated in vivo with production of anti-calcium-sensing receptor autoantibodies, which are typically found in AIRE-deficient patients. In addition, 9 months after bone marrow transplantation, patient 1 had Hashimoto thyroiditis, suggesting that organ-specific autoimmunity might be linked to nonhematopoietic cells, such as AIRE-expressing thymic epithelial cells. Deficiency of DNA-PKcs, a key AIRE partner, can present as an inflammatory disease with organ-specific autoimmunity, suggesting a role for DNA-PKcs in regulating autoimmune responses and maintaining AIRE-dependent tolerance in human subjects. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
    Full-text · Article · Apr 2015 · The Journal of allergy and clinical immunology
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    ABSTRACT: A reduction of ADA2 activity due to autosomal recessive loss of function mutations in CECR1 results in a newly described vasculopathic phenotype reminiscent of polyarteritis nodosa, with manifestations ranging from fatal systemic vasculitis with multiple strokes in children to limited cutaneous disease in middle-aged individuals. Evidence indicates that ADA2 is essential for the endothelial integrity of small vessels. However, CECR1 is not expressed, nor is the ADA2 protein detectable, in cultured human endothelial cells, thus implicating additional cell types or circulating factors in disease pathogenesis. Considering the phenotypic overlap of ADA2 deficiency with the type I interferonopathy Aicardi-Goutières syndrome due to mutations in SAMHD1, we looked for the presence of an interferon signature in the peripheral blood of two newly ascertained ADA2-deficient patients. We identified biallelic CECR1 mutations in two patients consistent with ADA2 deficiency. Both patients demonstrated an upregulation of interferon stimulated gene transcripts in peripheral blood. More strikingly however, genome-wide analysis revealed a marked overexpression of neutrophil-derived genes, suggesting that the vasculitis seen in ADA2 deficiency may be an indirect effect resulting from chronic and marked activity of neutrophils. We hypothesise that ADA2 may act as a regulator of neutrophil activation, and that a reduction of ADA2 activity results in significant endothelial damage via a neutrophil-driven process.
    Full-text · Article · Sep 2014 · Pediatric Rheumatology
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    Full-text · Article · Sep 2014 · Pediatric Rheumatology

  • No preview · Article · Sep 2014
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    Preview · Article · Aug 2014 · Nature Immunology
  • Nicole Fabien

    No preview · Article · Jul 2014 · Revue Francophone des Laboratoires
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    ABSTRACT: Coeliac disease is a complex autoimmune disease affecting patients of any age, who may present a wide variety of clinical manifestations. Different guidelines for the diagnosis and management of coeliac disease have been recently published. The aim of this study was to determine whether recommendations issued from these guidelines have been adopted by physicians in France when coeliac disease is suspected. A total of 5521 physicians were asked to fill in a detailed questionnaire about coeliac disease to evaluate their medical practice, as the type of symptoms leading to evoke coeliac disease, the prescription of duodenal biopsy and/or serologic tests, the type of serological tests (anti-tissue transglutaminase, anti-endomysium, anti-gliadin, anti-reticulin antibodies, total IgA dosage) prescribed to diagnose coeliac disease, notably. Response analysis of 256 general practitioners, 221 gastroenterologists, and 227 paediatricians showed that protean clinical presentations of coeliac disease may be better recognized by gastroenterologists and paediatricians than general practitioners. Gastroenterologists requested duodenal biopsy much more often than general practitioners and paediatricians when coeliac disease was suspected. Serologic testing behavior and knowledge of critical markers, as anti-tissue transglutaminase and total IgA dosage prescribed to diagnose coeliac disease, were different when comparing general practitioners, gastroenterologists and pediatricians. Analysis of medical prescriptions showed that the recommendations for coeliac disease diagnosis are not necessarily followed by physicians, emphasizing the fact that the impact of the national or international guidelines on medical behavior should be evaluated.
    No preview · Article · May 2014 · Journal of Digestive Diseases
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    ABSTRACT: To describe the clinical spectrum associated with aminoacyl-transfer RNA synthetase (ARS) autoantibodies in patients with idiopathic inflammatory myositis defined according to Peter and Bohan's criteria. Cohort studies were selected from MEDLINE and Embase up to August 2013. Two investigators independently extracted data on study design, patient characteristics, and clinical features (interstitial lung disease [ILD], fever, mechanic's hands [MH], Raynaud's phenomenon [RPh], arthralgia, sclerodactyly, cancer and dermatomyositis-specific rash) according to the presence of myositis-specific (anti-aminoacyl-transfer RNA synthetase [ARS], anti-signal recognition particle [anti-SRP] and anti-Mi2) and myositis-associated (anti-PM/Scl, anti-U1-RNP and anti-Ku) autoantibodies. 27 studies (3487 patients) were included in the meta-analysis. Arthralgia (75%, CI 67-81) and ILD (69%, CI 63-74) were the most prevalent clinical signs associated with anti-ARS autoantibodies. Anti-Mi2 and anti-SRP autoantibodies were associated with few extramuscular signs. ARS autoantibodies were identified in 13% of patients with cancer-associated myositis (5-25). Patients with non-anti-Jo1 ARS had greater odds of presenting fever (RR 0.63, CI 0.52-0.90) and ILD (RR 0.87, CI 0.81-0.93) compared to those with anti-Jo1 autoantibodies. The frequencies of myositis (RR 1.60, CI 1.38-1.85), arthralgia (RR 1.52, CI 1.32-1.76) and MH (RR 1.47, CI 1.11-1.94) were almost 50% higher in patients with anti-Jo1 compared to non-anti-Jo1 ARS autoantibodies. Patients with anti-PM/Scl differed from those with anti-ARS autoantibodies by a greater prevalence of RPh (RR 0.70, CI 0.53-0.94) and sclerodactyly (RR 0.47, CI 0.25-0.89). ILD was less frequent in patients with anti-U1-RNP autoantibodies (RR 3.35, CI 1.07-10.43). No difference was observed between anti-ARS and myositis-associated autoantibodies for other outcomes. The presence of anti-ARS autoantibodies delimits a heterogeneous subset of patients with a high prevalence of myositis, MH, arthralgia in anti-Jo1 patients, and RPh and fever in non-anti-Jo1 patients. The clinical signs of populations positive for anti-PM/Scl and anti-ARS autoantibodies largely overlap, especially with regard to ILD, challenging the clinical delimitation of the antisynthetase syndrome.
    Full-text · Article · Apr 2014 · Autoimmunity reviews
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    ABSTRACT: Objective The aim of our study was to compare in a cohort of 705 patients the diagnostic performance of two tests to detect autoantibodies to cyclic citrullinated peptides (CCP) and to determine whether a bead-based assay within a multiplex flow immunoassay (MFA) can be used instead of an enzyme linked immunosorbent assay (ELISA) technique in routine practice. Design and methods Six hundred and thirty patients with rheumatic symptoms and 75 patients with systemic lupus erythematosus (SLE) were tested for anti-CCP autoantibodies using two techniques: ELISA (Inova) and MFA (BioPlex®, Bio-Rad). Results Using kappa coefficient, there was an excellent agreement between ELISA and MFA when comparing 630 patients with rheumatic symptoms (κ coefficient, 0.82). In this cohort 174 patients were identified as suffering from RA, while 456 patients suffered from other diseases. Sensitivity and specificity of anti-CCP autoantibodies for RA was 70.7% and 92.3% for ELISA and 64.4% and 92.8% for MFA. The positive and negative predictive values were 77.4% and 89.2% for ELISA and 77.2% and 87.2% for MFA, respectively. There were no differences in the diagnostic performances between the two assays (Z = 0.67). The specificity of anti-CCP autoantibodies analysing patients with SLE was 97.3% with MFA and 96% with ELISA with an excellent agreement between the methods (98.7%; κ coefficient, 0.79). Conclusions Concordance between ELISA and MFA is high in routine practice. Overall, MFA is a powerful tool for rapid assessment of anti-CCP autoantibodies and can replace the ELISA technique, which could be used as a second-line test in some cases.
    No preview · Article · Apr 2014 · Clinical biochemistry
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    ABSTRACT: Introduction Amyopathic dermatomyositis associated with anti-MDA5 autoantibodies is a rare and very recently described clinical entity. Case report A 58-year-old woman was admitted with subacute onset of dyspnea (NYHA class IV) associated with cough, oligoarthritis of the wrists, myalgia and intermittent fever. Examination demonstrated skin lesions with heliotrope rash, Gottron's papules, “mechanics hands”, and basal inspiratory crackles on lung auscultation. Pulmonary function tests showed a restrictive ventilatory defect, with decreased carbon monoxide diffusion capacity and marked hypoxemia (PaO2 61 mmHg). The chest high-resolution computed tomography appearances were consistent with organizing pneumonia. Bronchoalveolar lavage differential cell count demonstrated 22 % neutrophils. Serum creatine kinase and electromyography were normal ; the serum ferritin level was elevated. Antinuclear antibodies were present and anti-MDA5 autoantibodies were identified. Significant improvement was obtained with systemic corticosteroids, later converted to mycophenolate mofetil as a steroid-sparing agent. Conclusion Amyopathic dermatomyositis associated with anti-MDA5 autoantibodies shares some characteristics with those associated with anti-synthetase antibodies. Muscular involvement may be mild or absent. Early diagnosis and treatment may improve outcome.
    No preview · Article · Mar 2014 · Revue des Maladies Respiratoires
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    ABSTRACT: Anti-nuclear antibodies (ANA) are fundamental for the diagnosis of autoimmune diseases, and have been determined by indirect immunofluorescence assay (IIFA) for decades. As the demand for ANA testing increased, alternative techniques were developed challenging the classic IIFA. These alternative platforms differ in their antigen profiles, sensitivity and specificity, raising uncertainties regarding standardisation and interpretation of incongruent results. Therefore, an international group of experts has created recommendations for ANA testing by different methods. Two groups of experts participated in this initiative. The European autoimmunity standardization initiative representing 15 European countries and the International Union of Immunologic Societies/World Health Organization/Arthritis Foundation/Centers for Disease Control and Prevention autoantibody standardising committee. A three-step process followed by a Delphi exercise with closed voting was applied. Twenty-five recommendations for determining ANA (1–13), anti-double stranded DNA antibodies (14–18), specific antibodies (19–23) and validation of methods (24–25) were created. Significant differences between experts were observed regarding recommendations 24–25 (p<0.03). Here, we formulated recommendations for the assessment and interpretation of ANA and associated antibodies. Notably, the roles of IIFA as a reference method, and the importance of defining nuclear and cytoplasmic staining, were emphasised, while the need to incorporate alternative automated methods was acknowledged. Various approaches to overcome discrepancies between methods were suggested of which an improved bench-to-bedside communication is of the utmost importance. These recommendations are based on current knowledge and can enable harmonisation of local algorithms for testing and evaluation of ANA and related autoantibodies. Last but not least, new more appropriate terminologies have been suggested.
    Full-text · Article · Jan 2014 · Annals of the Rheumatic Diseases

Publication Stats

2k Citations
386.08 Total Impact Points

Institutions

  • 2004-2016
    • Hospices Civils de Lyon
      Lyons, Rhône-Alpes, France
  • 1998-2015
    • Centre Hospitalier Lyon Sud
      Lyons, Rhône-Alpes, France
  • 2011
    • Cliniques Universitaires Saint-Luc
      • Division of Neurology
      Brussels, BRU, Belgium
  • 2009-2011
    • CHU de Lyon - Groupement Hospitalier Edouard Herriot
      Lyons, Rhône-Alpes, France
  • 2010
    • Claude Bernard University Lyon 1
      Villeurbanne, Rhône-Alpes, France
  • 2009-2010
    • University of Lyon
      Lyons, Rhône-Alpes, France
  • 1997-2010
    • French Institute of Health and Medical Research
      Lutetia Parisorum, Île-de-France, France
  • 2001
    • Hospital Clínic de Barcelona
      Barcino, Catalonia, Spain