Isabelle Touitou

Université Montpellier, Montpelhièr, Languedoc-Roussillon, France

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Publications (156)795.72 Total impact

  • American Journal of Medical Genetics Part A 09/2015; DOI:10.1002/ajmg.a.37374 · 2.16 Impact Factor
  • Guillaume Sarrabay · Isabelle Touitou
    Nature Reviews Rheumatology 08/2015; DOI:10.1038/nrrheum.2015.114 · 9.85 Impact Factor
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    ABSTRACT: To determine the type and frequency of musculoskeletal symptoms at onset and during follow-up of cryopyrin-associated periodic syndromes (CAPS). We retrospectively recorded the articular and muscular symptoms of patients with CAPS managed in French hospitals. Data were described as frequencies or median (range) and score groups were compared using the chi-square test, Fisher exact test, and Mann-Whitney test. 133 patients (33 children) were included, 20 with familial cold-induced auto-inflammatory syndrome, 88 with Muckle-Wells syndrome, 22 with chronic infantile neurologic cutaneous and articular syndrome, and 3 with unclassified CAPS. Median age was 35 (range 0-78) years at the time of the study, 1 (0-41) years at symptom onset, and 23 (0-58) years at diagnosis. The disease was sporadic in 17% of patients. Cutaneous symptoms predominated at onset (77%), followed by articular symptoms (30%). The p.Thr348Met and p.Arg260Trp NLRP3 mutations were significantly associated with presence and absence of articular symptoms at onset, respectively. During follow-up, 89% of patients had musculoskeletal symptoms; 88% had arthralgia and 58% arthritis, but only 9% had joint destruction. Tendinopathies occurred in 21.5% of patients, tender points in 16.5%, and myalgia in 33%. Only 3 patients had typical knee deformities. Radiographs were rarely performed. Except for bone deformities, osteoarticular symptoms occurred at similar frequencies in the different CAPS phenotypes. Joint manifestations were frequent in all CAPS phenotypes. Bone deformities were rare. Musculoskeletal manifestations varied within given families but tended to worsen over time. This article is protected by copyright. All rights reserved. © 2015, American College of Rheumatology.
    Arthritis and Rheumatology 08/2015; DOI:10.1002/art.39292
  • G Sarrabay · M Barat-Houari · S Annakib · I Touitou
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    ABSTRACT: Monogenic autoinflammatory diseases are defined as a group of conditions with a clinical and biological inflammatory syndrome but little or no evidence of autoimmunity. Over 17 years have passed since the discovery of the first autoinflammatory gene, MEFV, responsible for familial Mediterranean fever. Substantive progress has been made since then, highlighting the key role of the inflammasome in the maintenance of the cell homeostasis but also unravelling new pathophysiological pathways involved in these diseases. The history of autoinflammatory gene discovery demonstrates the powerfulness of next-generation sequencing approaches in linking inflammatory disorders with various overlapping phenotypes. It can be easily anticipated that new genes will be exponentially identified in the coming years. Integrating these new concepts should help to promote personalized patient care through novel therapeutic opportunities.
    Seminars in Immunopathology 05/2015; 37(4). DOI:10.1007/s00281-015-0495-3 · 7.75 Impact Factor
  • Guillaume Sarrabay · Sylvie Grandemange · Isabelle Touitou
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    ABSTRACT: Cryopyrin-associated periodic syndrome are rare autosomal dominantly inherited diseases. They include three overlapping phenotypes: familial cold autoinflammatory syndrome, Muckle-Wells syndrome, and chronic infantile neurological cutaneous articular syndrome/neonatal onset multisystem autoinflammatory syndrome (NOMID/CINCA). Recurrent fevers, joint pain, and urticarial skin rash are the main clinical features of these conditions. Renal amyloidosis and sensorineural complications may occur. Gain-of-function mutations in NLRP3 gene are responsible for the overactivation of the NLRP3 inflammasome, a multimolecular complex involved in the inflammatory process. Missense mutations are almost always encountered, particularly in exon 3, which encodes the nucleotide-binding domain. Mosaicism is not rare, especially in CINCA/NOMID. Next-generation sequencing will grant access to new insights about NLRP3 implication in oligogenic and multifactorial diseases.
    Expert Review of Clinical Immunology 05/2015; 11(7):1-9. DOI:10.1586/1744666X.2015.1047765 · 2.48 Impact Factor
  • Isabelle Koné-Paut · Véronique Hentgen · Isabelle Touitou
    New England Journal of Medicine 05/2015; 372(20):1970. DOI:10.1056/NEJMc1503146#SA1 · 55.87 Impact Factor
  • Archives de Pédiatrie 04/2015; 22(6). DOI:10.1016/j.arcped.2015.03.020 · 0.41 Impact Factor
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    ABSTRACT: Despite their limited licensed indications, anti-interleukin-1 (anti-IL-1) agents are often used in clinical practice for an increasing number of auto-inflammatory diseases. We conducted a national cross-sectional observational study from January 2011 to January 2013 to record the off-label use of such agents in France. We aimed to estimate the off-label use of anti-IL-1 treatments in France, assess their efficacy in rare diseases, and increase the reporting of their possible side effects. Physicians answered a questionnaire that covered patient and disease data, anti-IL-1 agent use, efficacy and adverse events. The study involved adult or paediatric patient who had received an anti-IL-1 agent after January 2005 in France. In total, 189 patients from 38 centres were included. The main diseases were adult-onset Still's disease (AOSD) (35), gout (28), systemic juvenile idiopathic arthritis (27), cryopyrin-associated periodic syndrome (CAPS) (21), familial Mediterranean fever (14) and mevalonate kinase deficiency (12). The main off-label used agent was anakinra, used at least once for 185 patients, with canakinumab used for 25. Anakinra was effective in most patients (90%), with higher complete clinical response rates for Schnitzler's syndrome, gout, CAPS and AOSD. Overall, 58% of patients showed at least one adverse event, mainly minor injection-site reactions. The main reported serious adverse event was severe infection. Injection-site reactions and liver toxicity were significantly more frequent in children than adults. The main non-cutaneous adverse event was liver toxicity, significantly associated with treatment duration. Weight gain was reported in about 10% of patients and was associated with treatment duration and CAPS. Canakinumab was rarely used and showed better cutaneous tolerance than anakinra but similar rates of non-cutaneous and severe adverse events. Anakinra was well tolerated and effective in most patients with various inflammatory diseases. The main adverse events were mild injection-site reactions, especially in children. The survey allowed for collecting limited information on the off-label use of canakinumab.
    Orphanet Journal of Rare Diseases 02/2015; 10(1):19. DOI:10.1186/s13023-015-0228-7 · 3.36 Impact Factor
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    ABSTRACT: The objective of this work was to develop and validate a set of clinical criteria for the classification of patients affected by periodic fevers. Patients with inherited periodic fevers (familial Mediterranean fever (FMF); mevalonate kinase deficiency (MKD); tumour necrosis factor receptor-associated periodic fever syndrome (TRAPS); cryopyrin-associated periodic syndromes (CAPS)) enrolled in the Eurofever Registry up until March 2013 were evaluated. Patients with periodic fever, aphthosis, pharyngitis and adenitis (PFAPA) syndrome were used as negative controls. For each genetic disease, patients were considered to be ‘gold standard’ on the basis of the presence of a confirmatory genetic analysis. Clinical criteria were formulated on the basis of univariate and multivariate analysis in an initial group of patients (training set) and validated in an independent set of patients (validation set). A total of 1215 consecutive patients with periodic fevers were identified, and 518 gold standard patients (291 FMF, 74 MKD, 86 TRAPS, 67 CAPS) and 199 patients with PFAPA as disease controls were evaluated. The univariate and multivariate analyses identified a number of clinical variables that correlated independently with each disease, and four provisional classification scores were created. Cut-off values of the classification scores were chosen using receiver operating characteristic curve analysis as those giving the highest sensitivity and specificity. The classification scores were then tested in an independent set of patients (validation set) with an area under the curve of 0.98 for FMF, 0.95 for TRAPS, 0.96 for MKD, and 0.99 for CAPS. In conclusion, evidence-based provisional clinical criteria with high sensitivity and specificity for the clinical classification of patients with inherited periodic fevers have been developed.
    Annals of the Rheumatic Diseases 01/2015; 74(5). DOI:10.1136/annrheumdis-2014-206580 · 10.38 Impact Factor
  • Pediatric Rheumatology 01/2015; 13(Suppl 1):O22. DOI:10.1186/1546-0096-13-S1-O22 · 1.61 Impact Factor
  • G Sarrabay · D Méchin · B Dumont · M André · I Touitou
    Pediatric Rheumatology 01/2015; 13(Suppl 1):O15. DOI:10.1186/1546-0096-13-S1-O15 · 1.61 Impact Factor
  • Pediatric Rheumatology 01/2015; 13(Suppl 1):P153. DOI:10.1186/1546-0096-13-S1-P153 · 1.61 Impact Factor
  • Pediatric Rheumatology 01/2015; 13(Suppl 1):P39. DOI:10.1186/1546-0096-13-S1-P39 · 1.61 Impact Factor
  • G Sarrabay · G Tachon · D Mechin · I Touitou
    Pediatric Rheumatology 01/2015; 13(Suppl 1):O17. DOI:10.1186/1546-0096-13-S1-O17 · 1.61 Impact Factor
  • Martina Witsch-Baumgartner · Isabelle Touitou
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    ABSTRACT: The European Journal of Human Genetics is the official Journal of the European Society of Human Genetics, publishing high-quality, original research papers, short reports, News and Commentary articles and reviews in the rapidly expanding field of human genetics and genomics.
    European journal of human genetics: EJHG 11/2014; 23(8). DOI:10.1038/ejhg.2014.257 · 4.35 Impact Factor
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    ABSTRACT: Adult onset Still's disease (AOSD) is a rare inflammatory disorder characterized by hectic spiking fever, evanescent rash and joint involvement. Prognosis is highly variable upon disease course and specific involvements, ranging from benign and limited outcome to chronic destructive polyarthritis and/or life-threatening events in case of visceral complications or reactive hemophagocytic lymphohistiocytosis (RHL). AOSD remains a debatable entity at the frontiers of autoimmune diseases and autoinflammatory disorders. The pivotal role of macrophage cell activation leading to a typical Th1 cytokine storm is now well established in AOSD, and confirmed by the benefits using treatments targeting TNF-α, IL-1β or IL-6 in refractory patients. However, it remains difficult to determine predictive factors of outcome and to draw guidelines for patient management. Herein, reviewing literature and relying on our experience in a series of 8 refractory AOSD patients, we question nosology and postulate that different cytokine patterns could underlie contrasting clinical expressions, as well as responses to targeted therapies. We therefore propose to dichotomize AOSD according to its clinical presentation. On the one hand, ‘systemic AOSD’ patients, exhibiting the highest inflammation process driven by excessive IL-18, IL-1β and IL-6 production, would be at risk of life-threatening complications (such as multivisceral involvements and RHL), and would preferentially respond to IL-1β and IL-6 antagonists. On the other hand, ‘rheumatic AOSD’ patients, exhibiting pre-eminence of joint involvement driven by IL-8 and IFN-γ production, would be at risk of articular destructions, and would preferentially respond to TNF-α blockers.
    Autoimmunity Reviews 11/2014; 13(11). DOI:10.1016/j.autrev.2014.08.032 · 7.93 Impact Factor
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    ABSTRACT: We report a case of discordant phenotypic sex in monozygotic twins mosaic 47,XXY/46,XX: monozygotic heterokaryotypic twins. The twins presented with cognitive and comprehension delay, behavioural and language disorders, all symptoms frequently reported in Klinefelter syndrome. Molecular zygosity analysis with several markers confirmed that the twins are in effect monozygotic (MZ). Array comparative genomic hybridization found no evidence for the implication of copy number variation in the phenotypes. Ultrasound scans of the reproductive organs revealed no abnormalities. Endocrine tests showed a low testosterone level in Twin 1 (male phenotype) and a low gonadotrophin level in Twin 2 (female phenotype) which, combined with the results from ultrasound examination, provided useful information for potentially predicting the future fertility potential of the twins. Blood karyotypes revealed the presence of a normal 46,XX cell line and an aneuploïd 47,XXY cell line in both patients. Examination of the chromosome constitutions of various tissues such as blood, buccal smear and urinary sediment not surprisingly showed different proportions for the 46,XX and 47,XXY cell lines, which most likely explains the discordant phenotypic sex and mild Klinefelter features. The most plausible underlying biological mechanism is a post-zygotic loss of the Y chromosome in an initially 47,XXY zygote. This would result in an embryo with both 46,XX and 47,XXY cells lines which could subsequently divide into two monozygotic embryos through a twinning process. The two cell lines would then be distributed differently between tissues which could result in phenotypic discordances in the twins. These observations emphasize the importance of regular paediatric evaluations to determine the optimal timing for fertility preservation measures and to detect new Klinefelter features which could appear throughout childhood in the two subjects.
    Human Reproduction 10/2014; 29(12). DOI:10.1093/humrep/deu275 · 4.57 Impact Factor
  • Revue du Rhumatisme 07/2014; 81(4). DOI:10.1016/j.rhum.2013.11.005
  • La Revue de Médecine Interne 06/2014; 35:A67. DOI:10.1016/j.revmed.2014.03.080 · 1.07 Impact Factor
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    ABSTRACT: Although biologic therapies have changed the course of rheumatoid arthritis (RA), today's major challenge remains to identify biomarkers to target treatments to selected patient groups. Circulating micro(mi)RNAs represent a novel class of molecular biomarkers whose expression is altered in RA. Our study aimed at quantifying miR-125b in blood and serum samples from RA patients, comparing healthy controls and patients with other forms of rheumatic diseases and arthritis, and evaluating its predictive value as biomarker for response to rituximab. Detectable levels of miR-125b were measured in total blood and serum samples and were significantly elevated in RA patients compared to osteoarthritic and healthy donors. The increase was however also found in patients with other forms of chronic inflammatory arthritis. Importantly, high serum levels of miR-125b at disease flare were associated with good clinical response to treatment with rituximab three months later (P = 0.002). This predictive value was not limited to RA as it was also found in patients with B lymphomas. Our results identify circulating miR-125b as a novel miRNA over expressed in RA and suggest that serum level of miR-125b is potential predictive biomarker of response to rituximab treatment.
    Mediators of Inflammation 03/2014; 2014(23):342524. DOI:10.1155/2014/342524 · 3.24 Impact Factor

Publication Stats

3k Citations
795.72 Total Impact Points


  • 2008–2015
    • Université Montpellier
      • Faculté de Médecine
      Montpelhièr, Languedoc-Roussillon, France
  • 2013
    • IRCCS Istituto G. Gaslini
      Genova, Liguria, Italy
  • 2011–2013
    • Université Montpellier 2 Sciences et Techniques
      Montpelhièr, Languedoc-Roussillon, France
  • 2012
    • CHRU de Strasbourg
      Strasburg, Alsace, France
  • 2007–2011
    • Centre Hospitalier Universitaire de Montpellier
      Montpelhièr, Languedoc-Roussillon, France
    • Assistance Publique – Hôpitaux de Paris
      Lutetia Parisorum, Île-de-France, France
  • 2010
    • Unité Inserm U1077
      Caen, Lower Normandy, France
  • 2007–2008
    • Hôpital Bicêtre (Hôpitaux Universitaires Paris-Sud)
      Lutetia Parisorum, Île-de-France, France
  • 2000–2004
    • Institut de Génétique Moléculaire de Montpellier
      Montpelhièr, Languedoc-Roussillon, France
  • 2003
    • French National Centre for Scientific Research
      Lutetia Parisorum, Île-de-France, France