Muriel Elhai

Publications (3)13.83 Total impact

• Article: Performance of Skin Ultrasound to Measure Skin Involvement in Different Animal Models of Systemic Sclerosis.

  Muriel Elhai, Jérôme Avouac, Carmen Marchiol, Gilles Renault, Barbara Ruiz, Maxime Fréchet, Gilles Chiocchia, Yannick Allanore
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  ABSTRACT: Animal models are widely used in systemic sclerosis (SSc) research. We set out to determine whether ultrasonography (US) could be used to assess skin fibrosis in two complementary SSc-models: the bleomycin-induced dermal fibrosis model and the tight-skin 1 mouse model. Back skin thickness was measured using a high-frequency ultrasound dedicated to the small animal. There was no significant difference in dermal thickness measured by US between mice injected with bleomycin and those treated with NaCl. These results were inconsistent with histological analyses. Mean US hypodermal thickness was significantly higher in tight-skin 1 mice as compared with Pa/Pa control subgroup (p = 0.02). Histologic and US measures of dermal and hypodermal thicknesses in this model were well correlated (r = 0.79). The intra-observer concordance was 0.96 for hypodermal thickness. US is reliable and sensitive in detecting hypodermal thickening in the tight-skin 1 mouse model. Further larger studies are warranted to better determine the place of US in SSc-research.
  Ultrasound in medicine & biology 02/2013; · 2.02 Impact Factor
• Article: Critical role of the adhesion receptor DNAX accessory molecule-1 (DNAM-1) in the development of inflammation-driven dermal fibrosis in a mouse model of systemic sclerosis.

  Jérôme Avouac, Muriel Elhai, Michal Tomcik, Barbara Ruiz, Manuel Friese, Melanie Piedavent, Marco Colonna, Gunter Bernhardt, André Kahan, Gilles Chiocchia, Jörg H W Distler, Yannick Allanore
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  ABSTRACT: OBJECTIVE: To investigate the contribution of the adhesion receptor DNAX accessory molecule-1 (DNAM-1) in the development of dermal fibrosis on gene inactivation and targeted molecular strategies. METHODS: Human skin expression of DNAM-1 was determined by immunohistochemistry. Mice deficient for DNAM-1 (dnam1(-/-)) and wild-type controls (dnam1(+/+)) were injected with bleomycin or NaCl. Infiltrating leucocytes, T cells, B cells and monocytes were quantified and inflammatory cytokines were measured in lesional skin of dnam1(-/-) and dnam1(+/+) mice. The anti-fibrotic potential of a DNAM-1 neutralising monoclonal antibody (mAb) was evaluated in the mouse model of bleomycin-induced dermal fibrosis. RESULTS: Overexpression of DNAM-1 was detected in the skin of patients with SSc (systemic sclerosis). Dnam1(-/-) mice were protected from bleomycin-induced dermal fibrosis with reduction of dermal thickening (75±5%, p=0.03), hydroxyproline content (46±8%, p=0.04) and myofibroblast counts (39±5%, p=0.01). Moreover, the number of T cells was significantly decreased in lesional skin of dnam1(-/-) mice (69±15%, p=0.0007). Dnam1(-/-) mice also displayed decreased levels of TNF-α and IL-6 in lesional skin. Consistent with the gene inactivation strategy, treatment of mice with DNAM-1 neutralising mAb prevented dermal fibrosis induced by bleomycin with reduction of dermal thickness (64±6%, p=0.002), hydroxyproline content (61±8%, p=0.004) and myofibroblast counts (83±12%, p=0.002). CONCLUSIONS: An inactivation gene strategy showed that DNAM-1 exerts profibrotic effects by controlling T cell activation and cytokine release. A molecular targeted strategy confirmed that DNAM-1 neutralising mAb has potent antifibrotic properties, supporting the hypothesis that inhibition of DNAM-1 might be a promising new approach for the treatment of SSc and potentially other related fibrotic diseases.
  Annals of the rheumatic diseases 11/2012; · 8.11 Impact Factor
• Article: Independent replication and metaanalysis of association studies establish TNFSF4 as a susceptibility gene preferentially associated with the subset of anticentromere-positive patients with systemic sclerosis.

  Baptiste Coustet, Matthieu Bouaziz, Philippe Dieudé, Mickael Guedj, Lara Bossini-Castillo, Sandeep Agarwal, Timothy Radstake, Javier Martin, Pravitt Gourh, Muriel Elhai, [......], Luc Mouthon, Camille Frances, Zahir Amoura, Patrick Carpentier, Anne Cosnes, Olivier Meyer, André Kahan, Catherine Boileau, Gilles Chiocchia, Yannick Allanore
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  ABSTRACT: Independent replication with large cohorts and metaanalysis of genetic associations are necessary to validate genetic susceptibility factors. The known tumor necrosis factor (ligand) superfamily, member 4 gene (TNFSF4) systemic lupus erythematosus (SLE) risk locus has been found to be associated with systemic sclerosis (SSc) in 2 studies, but with discrepancies between them for genotype-phenotype correlation. Our objective was to validate TNFSF4 association with SSc and determine the subset with the higher risk. Known SLE and SSc TNFSF4 susceptibility variants (rs2205960, rs1234317, rs12039904, rs10912580, and rs844648) were genotyped in 1031 patients with SSc and 1014 controls of French white ancestry. Genotype-phenotype association analysis and metaanalysis of available data were performed, providing a population study of 4989 patients with SSc and 4661 controls, all of European white ancestry. Allelic and genotypic associations were observed for the 5 single-nucleotide polymorphisms (SNP) with the subset of patients with SSc who are positive for anticentromere antibodies (ACA) and only a trend for association with SSc and limited cutaneous SSc. Rs2205960 exhibited the strongest allelic association in ACA+ patients with SSc [p = 0.0015; OR 1.37 (1.12-1.66)], with significant intra-cohort association when compared to patients with SSc positive for ACA. Metaanalysis confirmed overall association with SSc but also raised preferential association with the ACA+ subset and strongest effect with rs2205960 [T allele p = 0.00013; OR 1.33 (1.15-1.54) and TT genotype p = 0.00046; OR 2.02 (1.36-2.98)]. We confirm TNFSF4 as an SSc susceptibility gene and rs2205960 as a putative causal variant with preferential association in the ACA+ SSc subphenotype.
  The Journal of Rheumatology 03/2012; 39(5):997-1003. · 3.69 Impact Factor