K. P. Tiev

Assistance Publique – Hôpitaux de Paris, Lutetia Parisorum, Île-de-France, France

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Publications (191)459.22 Total impact

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    ABSTRACT: The multifunctional nuclear receptor peroxisome proliferator-activated receptor gamma (PPAR-γ) has potent anti-fibrotic effects, and its expression and activity are impaired in patients with systemic sclerosis (SSc). We investigated PPAR-γ gene (PPARG) single nucleotide polymorphisms (SNPs) associated with SSc. Tag SNPs spanning PPARG were genotyped in a European ancestry US discovery cohort comprising 152 SSc patients and 450 controls, with replication of our top signal in a European cohort (1031 SSc patients and 1014 controls from France). Clinical parameters and disease severity were analyzed to evaluate clinical associations with PPARG variants. In the discovery cohort, a single PPARG intronic SNP (rs10865710) was associated with SSc (p = 0.010; odds ratio = 1.52 per C allele, 95% confidence interval 1.10-2.08). This association was replicated in the French validation cohort (p = 0.052; odds ratio = 1.16 per C allele, 95% confidence interval 1.00-1.35). Meta-analysis of both cohorts indicated stronger evidence for association (p = 0.002; odds ratio = 1.22 per C allele, 95% confidence interval 1.07-1.40). The rs10865710 C allele was also associated with pulmonary arterial hypertension in the French SSc cohort (p = 0.002; odds ratio = 2.33 per C allele, 95% confidence interval 1.34-4.03). A PPARG variant is associated with susceptibility to SSc, consistent with a role of PPAR-γ in the pathogenesis of SSc.
    Arthritis Research & Therapy 05/2015; 17(1). DOI:10.1186/s13075-015-0641-2 · 3.75 Impact Factor
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    ABSTRACT: Periungueal capillaroscopy is a simple and reliable non-invasive technique allowing evaluation of cutaneous microcirculation. It was promoted for decades in patients with Raynaud's phenomenon in order to differentiate between the benign primary Raynaud's phenomenon and the secondary form in connective tissue diseases, especially systemic sclerosis. Nevertheless, the value of this procedure has also been shown in numerous pathologies such as diabetes or cardiovascular diseases. This literature review points to the versatility of this useful exam and its results in a large spectrum of diseases with microvascular involvement.
    La Revue de Médecine Interne 04/2015; DOI:10.1016/j.revmed.2015.03.015 · 1.32 Impact Factor
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    ABSTRACT: La pneumopathie interstitielle diffuse (PID) survient au cours de la sclérodermie systémique (ScS) et constitue l’une des principales causes de mortalité de la maladie. La prévalence de la PID associée à la ScS (PID-ScS) varie de 33 % à 100 % selon les méthodes diagnostiques. Les symptômes cliniques comme la dyspnée d’effort, la toux sèche et les douleurs thoraciques ne sont pas spécifiques et apparaissent souvent de façon tardive, impliquant d’autres explorations plus approfondies pour améliorer le diagnostic, le pronostic et le suivi thérapeutique. La tomodensitométrie pulmonaire en coupes fines est plus sensible que la radiographie traditionnelle dans la détection de la PID-ScS. Les explorations fonctionnelles respiratoires de par leur nature non invasive sont régulièrement utilisées pour évaluer le retentissement de la ScS sur la fonction respiratoire. La valeur diagnostique du lavage bronchoalvéolaire et des examens anatomopathologiques par biopsie pulmonaire demeure controversée. Ces examens sont néanmoins indispensables pour étudier les mécanismes physiopathologiques cellulaires et moléculaires de la PID-ScS. Plusieurs biomarqueurs sériques comme le surfactant-A (SP-A), -D (SP-D), la glycoprotéine Klebs de type mucine (KL-6) et la chimiokine CCL-18 ont été impliqués dans la PID-ScS. Leur concentration sérique est corrélée à la sévérité de la maladie. Enfin, la concentration alvéolaire du monoxyde d’azote mesurée dans l’air expiré permet de détecter précocement des patients sclérodermiques ayant un risque élevé d’aggravation de la fonction respiratoire. Un traitement précoce par immunosuppresseurs permettrait à ces patients d’éviter l’évolution de leur maladie vers la phase fibrosante irréversible de l’atteinte interstitielle pulmonaire.
    Revue de Pneumologie Clinique 11/2014; 70(6). DOI:10.1016/j.pneumo.2014.09.003 · 0.19 Impact Factor
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    T Hua-Huy · S Rivière · K P Tiev · A T Dinh-Xuan
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    ABSTRACT: Interstitial lung disease (ILD) is becoming one of the main causes of death of patients with systemic sclerosis (SSc). The prevalence of ILD associated with SSc (SSc-ILD) varies from 33% to 100% according to diagnostic methods. Clinical features such as dyspnea on exertion, dry cough, and chest pains are not specific and usually late-appearing, implying more specific tests in the diagnostic, prognosis, and follow-up of ILD in patients with SSc. High resolution thoracic CT scanner (HRCT) is more sensitive than chest X-ray in the detection of SSc-ILD. Pulmonary function tests (PFT) are non-invasive and periodically used to assess the impacts of SSc on respiratory function. Diagnostic values of bronchoalveolar lavage and histological examination on lung biopsy are controversial. However, these techniques are essential for studying cellular and molecular mechanisms underlying the pathophysiology of SSc-ILD. Several biomarkers such as surfactant-A (SP-A), -D (SP-D), mucin-like high molecular weight glycoprotein (KL-6), and chemokine CCL-18 have been implicated in SSc-PID. Serum levels of these proteins are correlated with the severity of SSc-ILD, as assessed by HRCT and/or PFT. Finally, alveolar concentration of exhaled nitric oxide can be used to screen SSc patients with high risk of deterioration of respiratory function, in whom immunosuppressant treatment could be useful in preventing the evolution to irreversible lung fibrosis. Copyright © 2014 Elsevier Masson SAS. All rights reserved.
    Revue de Pneumologie Clinique 11/2014; · 0.19 Impact Factor
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    ABSTRACT: Cyclophophamide (CYC) is not always effective in patients with scleroderma-related interstitial lung disease (SSc-ILD), hence the need for biomarkers able to predict beneficial responses to CYC therapy. We therefore assessed whether baseline alveolar concentration of nitric oxide (CANO) could predict the favourable response to CYC therapy in patients with SSc-ILD. Nineteen non-smoker patients with SSc-ILD, were enrolled and treated with 6 courses of CYC (0.75g/m2/monthly) for lung function decline the year before inclusion, and followed-up for 2 years period. We assessed the proportion of favourable response to CYC, defined as improvement of forced vital capacity (FVC) or total pulmonary capacity (TLC) more than 10% between the inclusion and each following visit, according to the validated cut-off of CANO at 8.5 ppb identifying progressive SSc-ILD subset. At inclusion, 7 patients out of 19 had CANO> 8.5 ppb. Clinical parameters were comparable between patients with high (>8.5 ppb) and low level of CANO (⩽ 8.5 ppb). After CYC therapy, and during the follow-up, 9 out of 19 patients had favourable response to CYC therapy, 10 did not meet responder's criteria, from whom 4 patients died from respiratory failure. Six out of 7 patients with CANO> 8.5 ppb at inclusion had favourable response to CYC therapy, while only 3 out of 12 patients with CANO⩽ 8.5 ppb responded favourably to CYC therapy (p=0.001). High level of CANO>8.5 ppb reflecting alveolar inflammation identify SSc patients with a greater chance to benefit from CYC treatment with a significant lung function improvement.
    Nitric Oxide 05/2014; 40. DOI:10.1016/j.niox.2014.04.011 · 3.18 Impact Factor
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    ABSTRACT: Background Watermelon stomach (WS) or Gastric Antral Vascular Ectasia (GAVE) is a very rare gastric complication of Systemic Sclerosis (SSc). It has a unique endoscopic appearance that is characterized by multiple longitudinal stripes of red vessels, which radiate in a spoke-like fashion from the pylorus to the antrum. The characteristics of patients with SSc-GAVE remain poorly described. Objectives The aim of this study was to determine the subgroup at risk together with the outcomes of SSc patients with GAVE. Methods We performed a retrospective, multicenter, international, case/control study. We collected cases of SSc-GAVE cases through EUSTAR network. Every case was matched with 2 SSc controls recruited from the same center, matched for age, sex, cutaneous subtype and disease duration. Disease characteristics were recorded at the time of GAVE occurrence and the last observation was used to defined the outcomes. Results We included 29 cases of SSc patients with GAVE, who were compared to 58 SSc controls. These 29 SSc patients (26 women, 89%) had a mean ± standard deviation (SD) age of 59±13 years and a mean ± SD disease duration of 7±3 years; 17 (59%) had the diffuse cutaneous subset and 12 (41%) the limited. Among these patients, 28 (97%) had anaemia, 13 (45%) needed red blood cell transfusion, and 18 (62%) required endoscopic treatment. In addition, SSc patients with GAVE were more likely to have positive anti-RNA polymerase-III antibodies (17/29, 60% vs. 8/58, 14%, p=0.0002), DLCO/AV<75% predicted (18/29, 61% vs. 14/58, 24%, p=0.005), and decreased frequency of anti-topoisomerase-I antibodies (1/29, 3% vs. 21/58, 36%, p=0.02) and pulmonary fibrosis (7/29, 24% vs. 33/58, 58%, p=0.007) compared to SSc patients without GAVE. The likelihood of other SSc-related disease characteristics were not different between cases and controls. Multivariate analysis including disease characteristics with a univariate P-value≤0.1 confirmed positive anti-RNA polymerase-III antibodies as an independent factor associated with GAVE (odds ratio: 5.76, 95% confidence interval 1.29-25.64, p=0.02). After a follow-up of 35±27 months, 7/29 (24%) had a relapse of bleeding requiring new local endoscopic treatment. Among these 7 patients, 5 needed red blood cell transfusion. Conclusions Presence of antibodies to RNA-Polymerase-III antibodies may be useful to identify the subset of SSc patients with increased risk for GAVE. Despite it was described as a late complication, SSc patients with GAVE had early disease duration in our cohort. GAVE appears as a cause of anaemia that clinicians should be aware of. This complication often requires local endoscopic therapy, which is usually efficient, despite frequent recurrent events. The inclusion of further cases in this ongoing project may help to better characterise the features of this rare complication. Disclosure of Interest None Declared
    Annals of the Rheumatic Diseases 01/2014; 71(Suppl 3):396-396. DOI:10.1136/annrheumdis-2012-eular.2699 · 10.38 Impact Factor
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    ABSTRACT: Cyclophosphamide (CYC) is not always effective in patients with scleroderma-related interstitial lung disease (SSc-ILD), hence the need for biomarkers able to predict beneficial responses to CYC therapy. We therefore assessed whether baseline alveolar concentration of nitric oxide (CANO) could predict the favourable response to CYC therapy in patients with SSc-ILD. Nineteen non-smoker patients with SSc-ILD, were enrolled and treated with 6 courses of CYC (0.75 g/m2/monthly) for lung function decline the year before inclusion, and followed-up for 2 years period. We assessed the proportion of favourable response to CYC, defined as improvement of forced vital capacity (FVC) or total pulmonary capacity (TLC) more than 10% between the inclusion and each following visit, according to the validated cut-off of CANO at 8.5 ppb identifying progressive SSc-ILD subset. At inclusion, 7 patients out of 19 had CANO >8.5 ppb. Clinical parameters were comparable between patients with high (>8.5 ppb) and low level of CANO (⩽8.5 ppb). After CYC therapy, and during the follow-up, 9 out of 19 patients had favourable response to CYC therapy, 10 did not meet responder’s criteria, from whom 4 patients died from respiratory failure. Six out of 7 patients with CANO >8.5 ppb at inclusion had favourable response to CYC therapy, while only 3 out of 12 patients with CANO ⩽8.5 ppb responded favourably to CYC therapy (p = 0.001). High level of CANO >8.5 ppb reflecting alveolar inflammation identify SSc patients with a greater chance to benefit from CYC treatment with a significant lung function improvement.
  • Mathieu Zmuda · Kiet Phong Tiev · Juliette Knoeri · Emmanuel Héron
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    ABSTRACT: Abstract Purpose: To report an experience with infliximab in severe corticosteroid-resistant Vogt-Koyanagi-Harada (VKH) disease. Design: Interventional case series. Methods: The medical records of 2 adult patients were reviewed. Results: Both patients had a visual acuity reduced to hand motion perception bilaterally after 1 month of high-dose corticosteroid therapy, due to multiple exudative retinal detachment involving the fovea. Visual acuity and OCT findings improved immediately after the first infliximab infusion, retinal detachments fully resolved after 1 month and visual acuity returned to normal within 6 months. Despite a negative pretreatment screening, one patient developed multivisceral tuberculosis, which led to infliximab discontinuation after the 7th infusion and was cured by a 9-month ambulatory antibiotic regimen. The other patient received 11 well-tolerated infliximab infusions. Respectively, 9 and 4 months after infliximab discontinuation both patients had normal vision and OCT findings. Conclusion: Infliximab showed tremendous therapeutic efficacy in sight-threatening corticosteroid-resistant VKH disease.
    Ocular immunology and inflammation 04/2013; 21(4). DOI:10.3109/09273948.2013.775312 · 1.44 Impact Factor
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    ABSTRACT: Opsonization and apoptotic cell elements are critical in systemic lupus erythematosus (SLE) and could act through the activation of the innate immunity. C-reactive protein (CRP) belongs to opsonins, and polymorphisms of CRP gene have been shown to be associated with SLE susceptibility. Accumulating evidences show that SLE and systemic sclerosis (SSc) share some genetic susceptibility factors. To determine whether polymorphisms of CRP confer susceptibility to SSc, four SNPs (rs1130864, rs1205, rs1800947 and rs1341665), chosen using Hapmap linkage disequilibrium data and published data, were genotyped in a cohort of 651 SSc patients (569 with antinuclear antibodies, 258 with anti-centromere and 153 with anti-topoisomerase I) and 442 controls. All individuals were of French Caucasian origin. The four polymorphisms were in Hardy-Weinberg equilibrium in the control population. Allelic and genotypic frequencies for these four polymorphisms were found to be similar in SSc patients and controls. Moreover, subphenotype analyses in particular for subgroups having antinuclear antibodies did not detect any difference between SSc patients and controls. These results obtained through a large cohort of European Caucasian SSc patients do not support the implication of CRP gene in the pathogenesis of SSc.
    Rheumatology International 02/2013; 34(3). DOI:10.1007/s00296-013-2673-8 · 1.63 Impact Factor
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    ABSTRACT: L’atteinte inflammatoire aortique infraclinique est très fréquente au cours de la maladie de Horton dont elle peut être la manifestation exclusive. Elle est souvent asymptomatique, peut disparaître sous traitement et est sans conséquences sur la survie dans la majorité des cas. Les patients atteints de maladie de Horton ont un risque relatif de développer une dissection ou un anévrisme de l’aorte thoracique de 17,3. Cette évolution vers une complication de l’aortite est actuellement difficile à prévoir et semble indépendante de l’activité de la maladie et des facteurs de risque cardiovasculaires. Le traitement n’est pas codifié pour les formes aortiques isolées, mais il est en général calqué sur celui de la maladie de Horton et modulé selon l’activité clinique et biologique de la maladie. La réalisation d’une TEP-tomodensitométrie systématique à la recherche d’une aortite infraclinique dans les formes typiques de maladie de Horton n’est pas justifiée actuellement. Le dépistage des complications de l’aortite n’a pas fait l’objet de recommandations, mais une radiographie thoracique et une échographie abdominale systématiques éventuellement complétées par une tomodensitométrie ou une imagerie par résonance magnétique (IRM) aortique se justifient lors du diagnostic de maladie de Horton à la recherche d’anévrismes d’indication chirurgicale.
    La Presse Médicale 02/2013; 42(2):151–159. DOI:10.1016/j.lpm.2012.03.003 · 1.17 Impact Factor
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    ABSTRACT: Fibrocytes are circulating precursors for fibroblasts. Blood fibrocytes are increased in patients with idiopathic pulmonary fibrosis (IPF). The aim of this study was to determine whether alveolar fibrocytes are detected in broncho-alveolar lavage (BAL), to identify their prognostic value, and their potential association with culture of fibroblasts from BAL. We quantified fibrocytes in BAL from 26 patients with IPF, 9 patients with Systemic Sclerosis(SSc)-interstitial lung disease (ILD), and 11 controls. BAL cells were cultured to isolate alveolar fibroblasts. Fibrocytes were detected in BAL in 14/26 IPF (54%) and 5/9 SSc patients (55%), and never in controls. Fibrocytes were in median 2.5% [0.4-19.7] and 3.0% [2.7-3.7] of BAL cells in IPF and SSc-ILD patients respectively. In IPF patients, the number of alveolar fibrocytes was correlated with the number of alveolar macrophages and was associated with a less severe disease but not with a better outcome. Fibroblasts were cultured from BAL in 12/26 IPF (46%), 5/9 SSc-ILD (65%) and never in controls. The detection of BAL fibrocytes did not predict a positive culture of fibroblasts. Fibrocytes were detected in BAL fluid in about half of the patients with IPF and SSc-ILD. Their number was associated with less severe disease in IPF patients and did not associate with the capacity to grow fibroblasts from BAL fluid.
    PLoS ONE 01/2013; 8(1):e53736. DOI:10.1371/journal.pone.0053736 · 3.23 Impact Factor
  • E. Héron · M. Zmuda · J. Knoeri · K.-P. Tiev
    La Revue de Médecine Interne 12/2012; 33:A144. DOI:10.1016/j.revmed.2012.10.243 · 1.32 Impact Factor
  • La Revue de Médecine Interne 12/2012; 33:A36–A37. DOI:10.1016/j.revmed.2012.10.028 · 1.32 Impact Factor
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    ABSTRACT: PURPOSE: To identify the diseases that are associated with a high plasma concentration of vitamin B12 and to measure the strength of this association. PATIENTS AND METHODS: Retrospective study including all admissions between 1st May, 2005 and 30th April, 2008 in the UMAG pole departments (emergency, internal medicine, acute geriatrics and medical intensive care) with a test for plasma vitamin B12. The association between each of medical information system codes (solid tumors, malignant hematologic process, and renal disease) and a high or low vitamin B12 concentration was measured by odds ratios (OR) from logistic models taking into account repeated admissions, with adjustment for age and the weighted Charlson index. RESULTS: Among 3702 admissions, 12% had a B12 more than 820pg/ml, 10.4% a B12 less than 180pg/ml and 77.6% a normal B12 concentration. After adjustment for age and the weighted Charlson index, high concentration of vitamin B12 was associated with interstitial renal diseases (OR 2.7; 95% CI: [1.7-4.2]), and cirrhosis or hepatitis (OR 4.3; [2.9-6.4]). After additional adjustment for these parameters, it was still associated with tumors (OR 1.8; [1.2-2.6]), malignant hematologic diseases (OR 2.1; [1.3-3.5]), metastasis (OR 2.9; [1.5-5.9]), liver metastasis (OR 6.2; [2.7-14.5]), liver carcinoma (LC) (OR 3.3; [1.1-10.4]), liver tumors other than LC (OR 4.7; [1.2-17.9]) and lymphoma (OR 3.2; [1.6-6.4]) but not with myeloma (OR 1.9; [0.6-1.4]). Low concentration of B12 was associated with myeloma (OR 2.9; [1.3-6.6]). CONCLUSION: Finding a high plasma concentration of vitamin B12 should lead to a systematic search for a hepatic disease or a tumor, and particularly for a hepatic localization of a tumor.
    La Revue de Médecine Interne 11/2012; 34(6). DOI:10.1016/j.revmed.2012.10.006 · 1.32 Impact Factor
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    ABSTRACT: Alveolar concentration of nitric oxide (C(A)NO) is a non invasive prognostic marker of systemic sclerosis (SSc) lung disease. There is, however, as yet no direct evidence showing concomitant increase of C(A)NO and the presence of inflammatory cells in alveoli. We have therefore measured C(A)NO and performed broncho-alveolar lavage (BAL) in SSc patients. Exhaled NO was measured, by the means of two different models, the two-compartment model (2CM) and the trumpet model with axial diffusion (TMAD), in 22 SSc patients and compared with 15 healthy controls. BAL was performed in all SSc patients. Alveolitis was defined as lymphocytes> 14%, polymorphonuclears> 4%, or eosinophils> 3% on cell count in BAL fluid. Comparisons of C(A)NO levels were made between SSc patients with, and without, alveolitis. Levels of C(A)NO were significantly higher in SSc patients as compared with controls (p<0.001). Median C(A)NO was significantly higher in SSc patients with alveolitis as compared with SSc patients without alveolitis (8.4 ppb; 1(st) and 3(rd) interquartile range: 6.0-10.5 vs 3.3 ppb; 2.2-3.5; p=0.004 for 2CM and 5.4 ppb; 3.2-9.2 vs 3.2 ppb; 1.4-3.3, p=0.02 for TMAD), while bronchial airway output of NO (J'aw NO, p= 0.19), and fractional exhaled NO (F(E)NO, p=0,12) were comparable. C(A)NO was consistently high in SSc patients with alveolitis irrespective of the methods chosen (TMAD or 2CM). Our findings showed that increased C(A)NO was associated with alveolitis in patients with SSc. We submit that C(A)NO could be used as a reliable non-invasive surrogate biomarker of alveolitis in scleroderma lung disease.
    Nitric Oxide 10/2012; 28. DOI:10.1016/j.niox.2012.10.005 · 3.18 Impact Factor
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    ABSTRACT: Systemic sclerosis (SSc)-related pulmonary arterial hypertension (PAH) has emerged as a major mortality prognostic factor. Mutations of transforming growth factor beta (TGFβ) receptor genes strongly contribute to idiopathic and familial PAH. To explore the genetic bases of SSc-PAH, we combined direct sequencing and genotyping of candidate genes encoding TGFβ receptor family members. TGFβ receptor genes, BMPR2, ALK1, TGFR2 and ENG, were sequenced in 10 SSc-PAH patients, nine SSc and seven controls. In addition, 22 single-nucleotide polymorphisms (SNP) of these four candidate genes were tested for association in a first set of 824 French Caucasian SSc patients (including 54 SSc-PAH) and 939 controls. The replication set consisted of 1516 European SSc (including 219 SSc-PAH) and 3129 controls from the European League Against Rheumatism Scleroderma Trials and Research group network. No mutation was identified by direct sequencing. However, two repertoried SNP, ENG rs35400405 and ALK1 rs2277382, were found in SSc-PAH patients only. The genotyping of 22 SNP including the latter showed that only rs2277382 was associated with SSc-PAH (p=0.0066, OR 2.13, 95% CI 1.24 to 3.65). Nevertheless, this was not replicated with the following result in combined analysis: p=0.123, OR 0.79, 95% CI 0.59 to 1.07. This study demonstrates the lack of association between these TGFβ receptor gene polymorphisms and SSc-PAH using both sequencing and genotyping methods.
    Annals of the rheumatic diseases 08/2012; 71(11):1900-3. DOI:10.1136/annrheumdis-2012-201755 · 10.38 Impact Factor
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    ABSTRACT: Systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) share some pathophysiologic bases as evidenced by individual and familial polyautoimmunity and common susceptibility genetic factors. With regard to the latter, there has been a recent shift from the "common variant" to the "rare variant" paradigm, since rare variants of TNFAIP3 and TREX1 with large effect sizes have recently been discovered in SLE. The present study was undertaken to investigate whether rare variants of TNFAIP3 and TREX1 are also associated with SSc. TREX1 single-nucleotide polymorphisms (SNPs) rs3135946, rs7626978, rs3135943, and rs11797 and TNFAIP3 SNPs rs9494883, rs72063345, rs5029939, rs2230926, rs117480515, and rs7749323 were genotyped in a discovery set (985 SSc patients and 1,011 controls), and replication analysis of the most relevant results was performed in a second set (622 SSc patients and 493 controls). No association between TREX1 variants and SSc was observed. For TNFAIP3, we first demonstrated that a low-frequency variant, rs117480515, tagged the recently identified TT>A SLE dinucleotide. In the discovery sample, we observed that all tested TNFAIP3 variants were in linkage disequilibrium and were associated with SSc and various SSc subsets, including the polyautoimmune phenotype. We subsequently genotyped rs117480515 in the replication sample and found it to be associated solely with the SSc polyautoimmune subset (odds ratio 3.51 [95% confidence interval 2.28-5.41], P = 8.58 × 10(-9) ) in the combined populations. Genotype-messenger RNA (mRNA) expression correlation analysis revealed that the TNFAIP3 rs117480515 risk allele was associated with decreased mRNA expression. The present findings establish the TNFAIP3 locus as a susceptibility factor for the subset of SSc with a polyautoimmune phenotype. Our results support the implication of rare/low-frequency functional variants and the critical role of A20 in autoimmunity.
    Arthritis & Rheumatology 08/2012; 64(8):2746-52. DOI:10.1002/art.34490 · 7.87 Impact Factor
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    ABSTRACT: Pulmonary embolism is a frequent disorder with a diagnostic approach based on probability estimation. Nevertheless, in some cases, prognosis may be impaired by delayed diagnosis resulting from atypical presenting manifestations. We report a 37-year-old woman, admitted for a seizure as the presenting manifestation of pulmonary embolism, and review nine additional similar cases reported in the literature since 1945. Seizures were always generalized tonico-clonic in nature without a past medical history of epilepsy in any case. Tachycardia was noted in nine patients over ten. Prognosis was usually severe leading to death by cardiovascular deficiency in 70% of cases. These observations suggest a systematic suspicion of pulmonary embolism in the presence of generalized convulsion with persistent tachycardia after resolution of the episode and no past medical history of seizures. More research is necessary to assess the role of d-dimer testing in these situations.
    La Revue de Médecine Interne 07/2012; 33(8):457-60. DOI:10.1016/j.revmed.2012.06.002 · 1.32 Impact Factor
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    ABSTRACT: Myopathy related to systemic sclerosis (Myo-SSc) is a disabling and unpredictable complication of SSc. We assessed the predictive value of serum aldolase, creatine kinase (CK), alanine transaminase (ALT), aspartate transaminase (AST) and C-reactive protein (CRP) to estimate the risk of developing Myo-SSc. We enrolled 137 SSc patients without proximal muscle weakness in a prospective monocentric study to follow them longitudinally over a four-year period. The risk of occurrence of Myo-SSc was ascertained according to the European NeuroMuscular Centre criteria and was analyzed according to levels of plasma aldolase, CK, transaminase enzymes and CRP at inclusion. Performance of each parameter to predict Myo-SSc occurrence was assessed and compared with the others. The area under the receiver operating characteristic curves (ROC) of plasma aldolase for Myo-SSc occurrence prediction was 0.80 (95% CI: 0.67 to 0.94, P < 0.001), which was higher than that of plasma CK (0.75, P = 0.01), and that of ALT (0.63, P = 0.04). AST and CRP had no predictive value for Myo-SSc occurrence. The best cut-off of aldolase for prediction of Myo-SSc occurrence within three years after inclusion was 9 U/L and higher than the upper normality limit (7 U/L), unlike that of CK and ALT. Myo-SSc occurred more frequently in patients whose plasma aldolase was higher than 9 U/L. Adjusted Hazard Ratio for patients with aldolase > 9 U/L was 10.3 (95% CI: 2.3 to 45.5), P < 0.001. Increased plasma aldolase level accurately identified SSc patients with high risk to develop subsequent Myo-SSc. This could help initiate appropriate treatment when the disabling muscle damage is still in a reversible stage.
    Arthritis research & therapy 06/2012; 14(3):R152. DOI:10.1186/ar3888 · 3.75 Impact Factor
  • La Revue de Médecine Interne 06/2012; 33:S56. DOI:10.1016/j.revmed.2012.03.045 · 1.32 Impact Factor

Publication Stats

2k Citations
459.22 Total Impact Points

Institutions

  • 2006–2013
    • Assistance Publique – Hôpitaux de Paris
      • Département de Médecine Interne
      Lutetia Parisorum, Île-de-France, France
    • Pierre and Marie Curie University - Paris 6
      • Laboratoire de biothérapies
      Lutetia Parisorum, Île-de-France, France
    • Université René Descartes - Paris 5
      • Faculté de Médecine
      Lutetia Parisorum, Île-de-France, France
  • 2010–2012
    • University of Paris-Est
      La Haye-Descartes, Centre, France
    • Centre Hospitalier Universitaire Rouen
      • Service d'Urologie
      Rouen, Upper Normandy, France
  • 2011
    • Paris Diderot University
      Lutetia Parisorum, Île-de-France, France
  • 2008
    • Hôpital Saint-Antoine (Hôpitaux Universitaires Est Parisien)
      • Service de Médecine Interne
      Paris, Ile-de-France, France
  • 2005
    • Université Montpellier
      Montpelhièr, Languedoc-Roussillon, France
    • French National Centre for Scientific Research
      Lutetia Parisorum, Île-de-France, France
  • 2003
    • Université Montpellier 2 Sciences et Techniques
      Montpelhièr, Languedoc-Roussillon, France
  • 2002
    • Université Libre de Bruxelles
      Bruxelles, Brussels Capital Region, Belgium