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L Mouthon

Publications and source records attributed to L Mouthon.

At least 19 recordsLinked to original sources
PubMed2006

Association between an endoglin gene polymorphism and systemic sclerosis-related pulmonary arterial hypertension.

UNLABELLED: Systemic sclerosis (SSc) is a connective tissue disorder characterized by early generalized microangiopathy with disturbed angiogenesis. Endoglin gene (ENG) encodes a transmembrane glycoprotein which acts as an accessory receptor for the transforming growth factor-beta (TGF-beta) superfamily, and is crucial for maintaining vascular integrity. A 6-base insertion in intron 7 (6bINS) of ENG has been reported to be associated with microvascular disturbance. OBJECTIVES: Our objective was to investigate the relationship between 6bINS and the vascular complication pulmonary arterial hypertension (PAH) in SSc in a French Caucasian population. METHODS: Two hundred eighty SSc cases containing 29/280 having PAH diagnosed by catheterism were compared with 140 patients with osteoarthritis. Genotyping was performed by polymerase-chain-reaction-based fluorescence and direct sequencing of genomic DNA. RESULTS: The polymorphism was in Hardy-Weinberg equilibrium. We observed a significant lower frequency of 6bINS allele in SSc patients with associated PAH compared with controls [10.3 vs 23.9%, P = 0.01; odds ratio (OR) 0.37, 95% confidence interval (CI) 0.15-0.89], and a trend in comparison with SSc patients without PAH (10.3 vs 20.3%, P = 0.05; OR: 0.45, 95% CI: 0.19-1.08). Genotypes carrying allele 6bINS were also less frequent in SSc patients with PAH than in controls (20.7 vs 42.9%, P = 0.02). CONCLUSIONS: Thus the frequency of 6bINS differs between SSc patients with or without PAH, suggesting the implication of ENG in this devastating vascular complication of SSc.

Adult↗
PubMed2006

Antibodies to fibroblasts in idiopathic and scleroderma-associated pulmonary hypertension.

The aim of the present study was to investigate the presence of anti-fibroblast antibodies in patients with idiopathic or scleroderma-associated pulmonary arterial hypertension (PAH) and healthy controls. PAH was documented by right-heart catheterisation (mean pulmonary artery pressure at rest >25 mmHg). Serum immunoglobulin (Ig)G and IgM reactivities of patients with idiopathic PAH (n = 35), scleroderma-associated PAH (n = 10), diffuse (n = 10) or limited cutaneous (n = 10) scleroderma without PAH and age- and sex-matched healthy individuals (n = 65) were analysed by cell-based ELISA and immunoblotting on normal human fibroblasts. As assessed by ELISA, 14 out of 35 (40%) patients with idiopathic PAH and three out of 10 (30%) patients with scleroderma-associated PAH expressed anti-fibroblast IgG antibodies. IgG from all individuals bound to one major 40-kDa protein band. IgG from patients with idiopathic PAH bound to two 25- and 60-kDa bands with a higher intensity than IgG from other individuals. In conclusion, immunoglobulin G anti-fibroblast antibodies are present in the serum of patients with pulmonary arterial hypertension. Immunoglobulin G from patients with idiopathic pulmonary arterial hypertension or scleroderma-associated pulmonary arterial hypertension express distinct reactivity profiles with fibroblasts antigens, suggesting distinct target antigens.

Adult↗
PubMed2006

Impact of pain in health related quality of life of patients with systemic sclerosis.

OBJECTIVES: Systemic sclerosis (SSc) has an heterogenous clinical pattern, with variable organ involvement and degrees of severity. Like in other rheumatic diseases, the self-questionnaires have been used to evaluate SSc globally. The aim of the study is as to evaluate the quality of life (QoL) in patients with either diffuse or limited SSc, and to examine the impact of pain on the QoL scores. METHODS: Patients with SSc, either diffuse or limited SSc, were included in a cross-sectional study. The QoL was evaluated with the short-form 36 (SF-36) and the functional repercussion with the SSc-modified Health Assessment Questionnaire (S-HAQ). RESULTS: A total of 89 patients (67 with diffuse and 22 with limited SSc) were included. The SF-36 score values were lower in SSc patients than those reported in the general population. The physical component scores (PCS) of the SF-36 was significantly worse in diffuse compared with limited SSc (P < 0.05). The PCS was significantly negatively related to the number of clinical manifestations (ANOVA, P < 0.0001). The mental component score (MCS) was not influenced by the type of SSc or the number of clinical manifestations presented by the patient. The QoL of SSc patients was highly correlated with pain (R = 0.69) and disability (R = 0.70). Interestingly, the QoL of SSc patients was only slightly correlated with cutaneous (R = 0.42) and pulmonary involvement (R = 0.57). CONCLUSION: The QoL of patients with SSc is strongly influenced by the type of SSc, the burden of clinical manifestations, the functional disability and by the pain, whatever its cause. The treatment of pain should be considered as priority to improve the QoL of SSc patients.

Adolescent↗
PubMed2006

[Eosinophil granule cationic proteins: eosinophil activation markers].

INTRODUCTION: Eosinophils play a central role in the pathogenesis of allergic diseases and host protection against parasites, especially against helminths. EXEGESIS: Eosinophil granules contain cytotoxic proteins, including cationic proteins: major basic protein (MBP), eosinophil cationic protein (ECP), eosinophil peroxidase (EPO) and eosinophil derived neurotoxin (EDN). CONCLUSION: Eosinophil granule proteins are implicated in the occurrence of allergic diseases and Churg-Strauss syndrome. These proteins are activation markers of eosinophils and may be useful in clinical practice.

Biomarkers↗
PubMed2006

Lack of association between the protein tyrosine phosphatase non-receptor 22 (PTPN22)*620W allele and systemic sclerosis in the French Caucasian population.

The minor allele of the R620W missense single-nucleotide polymorphism (SNP; rs2476601) in the PTPN22 (protein tyrosine phosphatase non-receptor 22) gene has been reported to be associated with multiple autoimmune diseases, including type 1 diabetes, systemic lupus erythematosus, rheumatoid arthritis, juvenile idiopathic arthritis, autoimmune thyroiditis and vitiligo. Systemic sclerosis (SSc) is a connective tissue disease with some autoimmune abnormalities. The aim of our study was to test for association of the PTPN22*620W allele with SSc in a French Caucasian cohort with a case-control study of 121 patients with SSc and 103 controls. All patients and controls were genotyped for the PTPN22*R620W SNP. No association was found between the PTPN22*620W allele and SSc (7% v 9.2%, p = 0.39). The frequency of genotypes carrying at least one 620W allele was similar in both groups (13% v 17%, p = 0.38). The PTPN22*620W allele was also not associated with autoantibody patterns. Thus, the PTPN22*R620W polymorphism cannot be regarded as a genetic susceptibility factor for SSc in the French Caucasian population.

Adult↗
PubMed2006

Increase of circulating neutrophil and platelet microparticles during acute vasculitis and hemodialysis.

Release of microparticles (MPs) from blood cells may occur upon various activation signals. MPs from neutrophil and platelet have been studied in systemic infectious diseases and cardiovascular diseases, respectively. They are here investigated in common nephropathies including vasculitis and dialysis, two conditions characterized by neutrophil activation. Flow cytometry analysis of neutrophil-derived (CD66b-positive) and platelet-derived (CD41a-positive) MPs was performed on 213 plasma samples from patients with various nephropathies, including 46 patients with vasculitis and 40 hemodialysis patients. MPs released ex vivo, during neutrophil activation in whole blood, were also measured in these patients. Correlations with clinical parameters and creatinine clearance were evaluated. The results show that MPs present in plasma from patients or healthy controls are from various origins: platelet-derived (38+/-22%), neutrophil-derived (2.8+/-3.8%) MPs, mixed aggregates of neutrophil/platelet MPs (28+/-15%) or neither from neutrophil or platelet (null) 31+/-20%. Acute vasculitis showed the highest level of all types of MPs, while other nephropathies did not result in significant changes of MP levels. A significant increase was observed during hemodialysis sessions. In patients with renal failure, no correlation was seen between MP levels and creatinine clearance. In conclusion, neutrophil and platelet MP levels are non-specific markers of neutrophil activation during vasculitis acute phase and dialysis-induced inflammation. Circulating aggregates of neutrophil/platelet MPs co-express adhesion molecules of both cell types and may be thus endowed with inflammation and coagulation- thus modulating properties.

Acute Disease↗
PubMed2006

Rituximab alone or in association with corticosteroids in the treatment of acquired factor VIII inhibitors: report of two cases.

Acquired haemophilia is a factor VIII (FVIII) deficiency due to autoantibodies directed against FVIII that can be responsible for severe haemorrhage. The therapeutic approach, in addition to the treatment of bleeding episodes with clotting factor infusion, relies on corticosteroids (CS), cyclophosphamide (CYC), and/or high-dose intravenous immunoglobulins (IVIg). However, the efficacy of IVIg is limited, and CS and CYC may cause a number of adverse effects. Recently, rituximab has been proposed, alone or in combination with CS and immunosuppressants in a small number of patients with acquired anti-FVIII antibodies with a good efficacy. We report here on two patients, aged 74 and 81, respectively, who developed acquired haemophilia, with high titre FVIII inhibitors and severe haemorrhage, in the absence of a detectable cause. Both of them received rituximab as a first line therapy with a marked and prolonged efficacy.

Adrenal Cortex Hormones↗
PubMed2005

[Intravenous immunoglobulins: therapeutic indications].

KEY POINTS: Intravenous immunoglobulins (IVIg) are preparations of normal human IgG obtained from large pools of healthy blood donors. IVIg can be used at low doses to treat patients with primary or secondary immune deficiencies and at high doses as an immunomodulatory agent in many autoimmune and systemic inflammatory diseases, especially hematologic and neurologic diseases. Its mechanisms of action are multiple, complex, and not yet well elucidated. Adverse effects are only rarely associated with IVIg. They are well tolerated, and the risk of transmission of infectious agents appears only theoretical.

Autoimmune Diseases↗
PubMed2005

[Pathogenesis of primary systemic vasculitides (I): ANCA-positive vasculitides].

The pathogenesis of different types of systemic vasculitis positive for antineutrophil cytoplasmic antibodies (ANCA) remains incompletely understood. ANCA constitute a heterogeneous group of antibodies that are associated with different types of small-vessel vasculitis, including Wegener's granulomatosis (WG), microscopic polyangiitis (MPA) and Churg-Strauss syndrome (CSS). Anti-proteinase 3 ANCA are present in more than 90% of patients with systemic WG, and anti-myeloperoxidase (MPO) ANCA in 50-75% of those with MPA and 40-60 % of those with CSS. The pathogenic role of ANCA has been well documented in vivo: passive transfer of anti-MPO ANCA in an MPO knockout mouse model immunized with MPO is sufficient to induce the disease. In vitro, mouse and human anti-proteinase 3 ANCA can activate neutrophils primed with TNF-a and contribute to vasculitic lesions. T-cells are also involved: type 1 helper cytokines have been detected in tissue lesions of limited forms of WG, while type 2 helper cytokines have been identified in its systemic forms. Eosinophils may play a key role in the development of vasculitic lesions in CSS, although this remains to be proved.

Adoptive Transfer↗
PubMed2005

[Pathogenesis of primary systemic vasculitides (II): ANCA-negative vasculitides].

The pathogenesis of different types of systemic vasculitis negative for antineutrophil cytoplasm antibodies (ANCA) and involving small or medium-sized vessels is not very well documented. During polyarteritis nodosa (PAN), which is related to hepatitis B virus (HBV) infection, as well as during cryoglobulinemic vasculitides, associated with hepatitis C virus (HCV), and probably during Henoch Schönlein purpura, histological lesions may result from the deposition of immune complexes formed from viral antigens and from antibodies responsible for the activation of the classic complement pathway and for recruitment of polymorphonuclear neutrophils. Two other mechanisms are discussed for other types of ANCA-negative systemic vasculitis: immune complex deposition and sheer stress at arterial bifurcation points. A bacterial superantigen is suspected in Kawasaki disease but remains unproved.

Animals↗
PubMed2005

Anti-endothelial cell antibodies in idiopathic and systemic sclerosis associated pulmonary arterial hypertension.

BACKGROUND: It has previously been shown that IgG antibodies from patients with limited cutaneous systemic sclerosis (SSc) bind to specific microvascular endothelial cell antigens. Since patients with limited cutaneous SSc are prone to develop pulmonary arterial hypertension (PAH), and since endothelial cell activation is involved in the pathogenesis of idiopathic PAH (IPAH), a study was undertaken to examine the presence of anti-endothelial cell antibodies in patients with idiopathic or SSc associated PAH. METHODS: PAH was confirmed by right heart catheterisation (mean pulmonary artery pressure at rest >25 mm Hg). Serum IgG and IgM reactivities were analysed by immunoblotting on human macrovascular and microvascular lung and dermal endothelial cells from patients with IPAH (n = 35), patients with PAH associated with SSc (n = 10), patients with diffuse (n = 10) or limited cutaneous (n = 10) SSc without PAH, and 65 age and sex matched healthy individuals. RESULTS: IgG antibodies from patients with IPAH bound to a 36 kDa band in macrovascular endothelial cell extracts with a higher intensity than IgG from other patient groups and controls. IgG antibodies from patients with IPAH bound more strongly to a 58 kDa band in microvascular dermal endothelial cells and to a 53 kDa band in microvascular lung endothelial cells than IgG antibodies from other patients and controls. IgG antibodies from patients with limited cutaneous SSc with or without PAH, but not from other groups or from healthy controls, bound to two major bands (75 kDa and 85 kDa) in microvascular endothelial cells. CONCLUSION: IgG antibodies from patients with idiopathic or SSc associated PAH express distinct reactivity profiles with macrovascular and microvascular endothelial cell antigens.

Adult↗
PubMed2005

Evolution of previous sarcoidosis under type 1 interferons given for severe associated disease.

Sarcoidosis is a granulomatous disorder with a well-known T helper (Th) type 1 cell commitment and a key pathogenic role of interferon (IFN)-gamma. However, little is known about the influence of type 1 IFNs, such as IFN-alpha and IFN-beta, on the course of previous sarcoidosis. The aim of this study was to determine whether type 1 IFNs can safely be used in patients with sarcoidosis for severe associated disease. The present study examined a series of four patients with sarcoidosis, treated by IFN-alpha or IFN-beta for viral hepatitis (three cases) or multiple sclerosis (one case). IFN was initiated soon after apparent recovery (three cases) or during a worsening phase of sarcoidosis (one case). Hydroxychloroquine was added in the case with active disease. Patients received interferon for 6-24 months and had close monitoring during and after IFN therapy. Interestingly, no recurrence or exacerbation of sarcoidosis had occurred at 4 yrs of follow up. Two patients were cured from viral hepatitis, whilst treatment for another failed. No neurological progression was observed in the remaining patient. This series suggests that, despite the T helper type 1 phenotype of sarcoid granulomatous reaction, type 1 interferons do not exacerbate sarcoidosis in remission and this makes their use possible if indicated. However, their effect in persistent forms of the disease needs further evaluation.

Adult↗
PubMed2004

Validation of French version of the Scleroderma Health Assessment Questionnaire (SSc HAQ).

The modified Scleroderma Health Assessment Questionnaire (SSc HAQ) is a functional score to assess systemic sclerosis (SSc) comprising the HAQ disease index (HAQ-DI) plus five specific visual analogue scales (VAS). Since it was validated in English-speaking patients only, its general use in any other language necessitates prior cross-cultural adaptation and validation. We designed this study to assess its value in French-speaking patients and to validate the French version according to international recommendations. We elaborated a French version using the "forward-backward" method. We then validated its psychometric properties with 100 consecutive SSc French-speaking patients who had undergone simultaneous clinical and paraclinical examination. In addition, we calculated the SSc HAQ score, a new outcome measure, which is obtained by pooling the eight domains from the HAQ-DI with the five organ VAS. Our study confirmed the psychometric properties of the SSc HAQ in non-English-speaking patients with (a) structural validity: the major component analysis, performed on the HAQ-DI and the five VAS, yielding a two-factor structure; (b) convergent validity: with high correlation coefficients between the SSc HAQ score and the physical component score of the SF-36 (r=-0.74, p<0.0001); (c) discriminant validity: the SSc HAQ score was better in patients with limited than with diffuse SSc (0.5+/-0.5 vs 1.1+/-0.7, respectively, p<0.0001) in relation to the number of clinical involvements; (d) reproducibility was high using the test-retest procedure (r=0.98). This study showed the value of the SSc HAQ, which is a simple, discriminant, reproducible self-administered questionnaire to evaluate French-speaking SSc patients. In addition, we suggest the use of a new outcome measure, the SSc HAQ score, to assess this systemic disease more accurately.

Disability Evaluation↗
PubMed2004

Prevalence of systemic sclerosis in a French multi-ethnic county.

OBJECTIVE: To assess the prevalence of systemic sclerosis (SSc) in a French multi-ethnic population and to examine ethnic differences. METHODS: This survey was conducted in Seine-Saint-Denis County, a suburb of Paris, home to 1,094,412 adults (>/=15 yr), among whom 26% are of non-European background with mainly northern and sub-Saharan African, Asian and Caribbean ancestries. The study period comprised the entire calendar year 2001. Patients were ascertained through four sources: public and private hospitals, general practitioners and community specialists, the French SSc patient support group, and the National Public Health Insurance System database. Only cases meeting either the 1980 ACR and/or LeRoy and Medsger's classification criteria were included and assigned to three clinical subsets: limited (normal skin) (l), limited cutaneous (lc) or diffuse cutaneous (dc) SSc. Capture-recapture (CR) analyses using log-linear modelling were performed to correct for incomplete case finding. RESULTS: We retained a total of 119 patients with SSc, including 15 extrapolated from inaccessible files. CR analysis estimated that 54.2 additional cases were missed by all the sources. The overall SSc prevalence (per million adults) was 158.3 (95% confidence interval, 129-187); those of lSSc, lcSSc and dcSSc were, respectively, 32.3 (16-48), 83.1 (66-101) and 42.9 (25-60); and respective values for Europeans and non-Europeans were 140.2 (112-170) and 210.8 (128-293). CONCLUSION: Regarding the heterogeneity of previously published estimates, this population-based survey using CR analysis might contribute to obtaining a better appraisal of SSc prevalence. Despite overlapping confidence intervals, the higher prevalence observed for non-Europeans could support potential influences of ethnic origin on the pathogenesis of SSc.

Adult↗
PubMed2004

[Quality of life assessment with the MOS-SF36 in patients with systemic sclerosis].

OBJECTIVE: To investigate the metric properties and the validity of the Medical Outcome Study Short Form 36 (SF-36), a questionnaire to assess the quality of life, in patients with either diffuse or limited systemic sclerosis (SS), and to examine the effect of the disease on quality of life. METHODS: Cross sectional study of 86 patients with a SS (64 diffuse SS, 22 limited SS). Disease severity was assessed by clinical examination, pulmonary functional tests and Health Assessment Questionnaire (HAQ) modified for scleroderma. RESULTS: The SF-36 scores values were lower in diffuse than in limited sclérodermie systémique. The Physical Component Score was worse in patients with than without any clinical involvement. This score increased in relation with the number of clinical involvements. The quality of life of patients with SS was correlated to its functional repercussion. CONCLUSION: The quality of life in SS patients is correlated with the clinical severity of the disease. The use of SF-36 to measure the quality of life is useful for the clinical evaluation of patients with SS.

Adolescent↗