Nicole Fabien

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

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Publications (106)324.06 Total impact

  • European Respiratory Review 06/2015; 24(136):370-2. DOI:10.1183/16000617.00006714
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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.
    European Respiratory Review 06/2015; 24(136):216-38. DOI:10.1183/16000617.00002015
  • La Revue de Médecine Interne 06/2015; 36:A66. DOI:10.1016/j.revmed.2015.03.311 · 1.32 Impact Factor
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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.
    Gastroentérologie Clinique et Biologique 05/2015; DOI:10.1016/j.clinre.2015.03.006 · 1.98 Impact Factor
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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.
    The Journal of allergy and clinical immunology 04/2015; 27. DOI:10.1016/j.jaci.2015.01.040 · 11.25 Impact Factor
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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.
    Pediatric Rheumatology 09/2014; 12(1):44. DOI:10.1186/1546-0096-12-44 · 1.62 Impact Factor
  • Nicole Fabien
    Revue Francophone des Laboratoires 07/2014; 2014(464):45–47. DOI:10.1016/S1773-035X(14)72599-7
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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.
    Journal of Digestive Diseases 05/2014; 15(8). DOI:10.1111/1751-2980.12158 · 1.92 Impact Factor
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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.
    Autoimmunity reviews 04/2014; 13(9). DOI:10.1016/j.autrev.2014.03.004 · 7.10 Impact Factor
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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.
    Clinical biochemistry 04/2014; 47(6). DOI:10.1016/j.clinbiochem.2014.02.010 · 2.23 Impact Factor
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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.
    Revue des Maladies Respiratoires 03/2014; DOI:10.1016/j.rmr.2014.02.010 · 0.49 Impact Factor
  • La Revue de Médecine Interne 12/2013; 34:A62-A63. DOI:10.1016/j.revmed.2013.10.093 · 1.32 Impact Factor
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    ABSTRACT: Objective: Systemic lupus erythematosus (SLE) is a prototype autoimmune disease, assumed to occur due to a complex interplay of environmental and genetic factors. Rare causes of monogenic SLE have been described, providing unique insights into fundamental mechanisms of immune tolerance. Here, our objective was to identify the cause of an autosomal recessive form of SLE. Methods: We investigated three siblings from one consanguineous kindred with juvenile-onset SLE and used next generation sequencing to identify mutations in the disease-associated gene. We performed extensive biochemical, immunological and functional assays to assess the impact of the identified mutations on B cell biology. Results: We identified a homozygous missense mutation in PRKCD, encoding protein kinase delta (PKCδ) in all three affected siblings. Mutation of PRKCD resulted in reduced expression and activity of the encoded protein PKCδ, involved in the deletion of autoreactive B cells, leading to a resistance to BCR- and calcium-dependent apoptosis and increased B cell proliferation. Thus, as for mice deficient in PKCδ, which exhibit an SLE phenotype and B cell expansion, we observed an increase of immature B cells in affected patients, and a developmental shift toward an immature phenotype of naïve B cells. Conclusion: Our findings indicate that PKCδ is crucial in regulating B cell tolerance and preventing self-reactivity in humans, and that PKCδ deficiency represents a novel genetic defect of apoptosis leading to SLE. © 2013 American College of Rheumatology.
    Arthritis & Rheumatology 05/2013; 65(8). DOI:10.1002/art.38008 · 7.87 Impact Factor
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    ABSTRACT: To assess the performance of commercial anti-ganglioside antibody assays, we determined anti-ganglioside antibody IgG and IgM isotype profiles of patients with acute and chronic well-characterized immune-mediated peripheral neuropathies by one immunodot assays (Zentec/Ingen: Dotzen Ganglio Profile Ab, Euroimmun/BioAdvance: Euroline ganglioprofile), two line-immuno assay (GA Generic Assays/Labodia: Anti-Gangli osid Dot, Euroimmun/BioAdvance: Euroline ganglioprofile), and one enzyme-linked immunosorbent assay (ELISA) (Bühlmann: GanglioCombi). Specific antibody profiles were compared with those obtained by our validated standard in-house immunodot assay (IDA). We selected 33 sera with high levels of IgG and IgM anti-ganglioside antibodies from 15 patients with Guillain-Barre syndrome (GBS) subtypes and variants, 12 patients with CANOMAD syndrome (chronic ataxic neuropathy with ophthalmoplegia, M-paraprotein, cold agglutinins, disialosyl antibodies), 5 patients with chronic motor peripheral neuropathies, and 1 patient with sensory neuropathy and a control group composed of 10 patients with non-autoimmune neuropathy. The 3 commercial IDAs employing hydrophobic membranes and the ELISA demonstrated different carbohydrate epitopes on 6 to 12 glycolipid antigens used for anti-ganglioside antibody detection. Comparison with the validated in-house IDA showed large variations in sensitivity between tests and a more diverse reactivity to gangliosides than expected. The test with the largest panel of glycolipids detecting 11 anti-ganglioside antibody reactivities (GM1, GM2, GM3, GM4, GD1a, GD1b, GD2, GD3, GT1a, GT1b, GQ1b, and sulfatide) revealed the best concordance with our in-house assay. However, even with this test, differences were observed in the immunoreactivity against some gangliosides and weakly stained bands were not easy to interpret. Our data suggest an urgent need for standardization of commercial anti-ganglioside assays and the introduction of international anti-ganglioside antibody reference standards.
    Clinical laboratory 01/2013; 59(11-12):1277-87. DOI:10.7754/Clin.Lab.2013.121116 · 1.08 Impact Factor
  • La Revue de Médecine Interne 12/2012; 33:A73. DOI:10.1016/j.revmed.2012.10.098 · 1.32 Impact Factor
  • La Revue de Médecine Interne 12/2012; 33:A70-A71. DOI:10.1016/j.revmed.2012.10.094 · 1.32 Impact Factor
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  • Nicole Fabien
    Revue Francophone des Laboratoires 07/2012; 2012(444):18–24. DOI:10.1016/S1773-035X(12)71520-4
  • La Revue de Médecine Interne 12/2011; 32:S291–S292. DOI:10.1016/j.revmed.2011.10.355 · 1.32 Impact Factor
  • Article: Reply.
    Muscle & Nerve 10/2011; 44(4):612. DOI:10.1002/mus.22197 · 2.31 Impact Factor

Publication Stats

2k Citations
324.06 Total Impact Points


  • 2004–2015
    • Hospices Civils de Lyon
      Lyons, Rhône-Alpes, France
  • 1998–2012
    • 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
  • 2008–2011
    • University of Lyon
      Lyons, Rhône-Alpes, France
  • 2010
    • Claude Bernard University Lyon 1
      Villeurbanne, Rhône-Alpes, France
  • 1996–2010
    • French Institute of Health and Medical Research
      Lutetia Parisorum, Île-de-France, France