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Maxime Dougados,
Maria-Antonietta d'Agostino, Joëlle Benessiano,
Francis Berenbaum,
Maxime Breban,
Pascal Claudepierre,
Bernard Combe,
Patricia Dargent-Molina,
Jean-Pierre Daurès,
Bruno Fautrel, [......],
Véronique Leblanc,
Isabelle Logeart,
Thao Pham,
Pascal Richette,
Christian Roux,
Martin Rudwaleit,
Alain Saraux,
Jean-Marc Treluyer,
Désirée van der Heijde,
Daniel Wendling
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ABSTRACT: The French Society of Rheumatology has initiated a large national multicenter, longitudinal, prospective follow-up of patients presenting with early inflammatory back pain in order to set up a database to facilitate several investigations on diagnosis, prognosis, epidemiology, pathogenesis and medico-economics in the field of early inflammatory back pain and spondyloarthritis.
Patients were recruited if they had inflammatory back pain of more than 3 months and less than 3 years. Patients will be followed every 6 months during the first 2 years then every year during at least 5years. Apart from information collected on a Case Report Form (demographics, disease activity, severity, co-morbidities, socio-economics, treatments, radiological and MRI evaluation of the spine and the pelvis according to the local investigators, and for some centers bone densitometry and ultrasonography of entheses), the digital X-rays and MRI of the spine and pelvis are stored using a specific software (Carestream) and the biological samples (DNA, RNA, sera, urines) are centralized at the Biological Resources Center (Bichat Hospital).
The recruitment period of the 708 patients (mean age: 34±9years, female 54%, HLA-B27 positive: 57%) in the 25 centers was 26 months (from December 2007 to April 2010). The modified New York criteria, Amor criteria, ESSG criteria and axial ASAS criteria were fulfilled by 26%, 77%, 76% and 67% of the patients at entry, respectively. A history or current symptoms suggestive of peripheral arthritis, acute anterior uveitis and inflammatory bowel disease were observed in 21%, 9% and 4% of the patients, respectively. The disease was active (BASDAI: 45±20) despite an NSAID intake in 66% of the patients.
This large cohort should facilitate the conduct of researches in different areas (clinical, medico-economics, translational) in order to improve our knowledge on the pathogenesis and natural history of axial spondyloarthritis.
Joint, bone, spine: revue du rhumatisme 03/2011; 78(6):598-603. · 2.25 Impact Factor
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ABSTRACT: Type II secretory phospholipase A(2) (sPLA(2)-IIA) is widely expressed in various cell types and may trigger local inflammatory responses. We sought to evaluate whether systemic sPLA(2) is associated with prognosis in patients with coronary heart disease (CHD).
Plasma concentrations of sPLA(2) (ELISA) and sPLA(2) activity (selective fluorometric assay) were measured at baseline in a cohort of 1024 patients aged 30-70 years with CHD. The Cox-proportional hazards model was used to determine the prognostic value of sPLA(2) on a combined cardiovascular disease (CVD) endpoint after adjustment for covariates. During a mean follow-up of 4.1 years, 93 patients (9.1%) experienced a secondary CVD event. In a multivariable model, sPLA(2) mass and activity were associated with hazard ratios of secondary CVD events of 2.07 (95% CI, 1.17-3.66) and 1.65 (95% CI 0.96-2.84) for mass and activity, respectively, when extreme tertiles were compared. Further adjustment for cystatin C, N-terminal-probrain natriuretic peptide, C-reactive protein, and lipoprotein-associated phospholipase A(2) attenuated the associations, still showing a positive trend for mass but a less clear pattern for activity. However, when sPLA(2) mass and activity were analysed as continuous variables both still showed a statistically significant increase in risk in all models.
Secretory phospholipase A(2) mass and activity appear to be predictive of secondary CVD events in patients with CHD.
European Heart Journal 09/2009; 30(22):2742-8. · 10.48 Impact Factor
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Bernard Combe, Joëlle Benessiano,
Francis Berenbaum,
Alain Cantagrel,
Jean-Pierre Daurès,
Maxime Dougados,
Patrice Fardellone,
Bruno Fautrel,
Réné-Marc Flipo,
Philippe Goupille,
Francis Guillemin,
Xavier Le Loet,
Isabelle Logeart,
Xavier Mariette,
Olvier Meyer,
Philippe Ravaud,
Nathalie Rincheval,
Alain Saraux,
Thierry Schaeverbeke,
Jean Sibilia
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ABSTRACT: The French Society of Rheumatology initiated a large national multicenter, longitudinal and prospective cohort, the so-called "ESPOIR cohort study" in order to set up databases to allow various investigations on diagnosis, prognostic markers, epidemiology, pathogenesis and medico-economic factors in the field of early arthritis and rheumatoid arthritis.
Patients were recruited if they had undifferentiated arthritis or rheumatoid arthritis, of less than 6 months disease duration and if they were DMARD and steroids naïve. Patients have then to be followed every 6 months during the first 2 years then every year during at least 10 years. Clinical, biological, radiographic and medico-economic databases have been constituted to fit in the different objectives of the project and more than 20 scientific studies have already been accepted by the scientific committee.
813 patients were included (76.75% were female). The mean age was 48.07+/-12.55 years. The mean delay from the onset of symptoms to referral to the rheumatologist was 74.8+/-76.6 days. Baseline swollen and tender joint counts were 7.19+/-5.37 and 8.43+/-7.01; DAS28 score was 5.11+/-1.31. CRP was abnormal in 38.9% of the patients; 44.2%, 45.8% and 38.8% had respectively IgM rheumatoid factor (RF), IgA RF and anti-CCP antibodies. HLA DRB1*01 or 04 genes were found in 56.7% of them. Finally, 22% of these patients had erosions on hand or feet at baseline.
Joint, bone, spine: revue du rhumatisme 11/2007; 74(5):440-5. · 2.25 Impact Factor
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Camille Taillé,
Armelle Guénégou,
Abdelhamid Almolki,
Marie Piperaud,
Bénédicte Leynaert,
Sandrine Vuillaumier,
Françoise Neukirch,
Jorge Boczkowski,
Michel Aubier, Joëlle Benessiano,
Bruno Crestani
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ABSTRACT: Endothelin-1 (EDN1) has been involved in the development of airway obstruction and inflammation in asthma. Several polymorphisms have been identified among the genes encoding for preproET1, an inactive precursor of ET-1, and for ETA (EDNRA) and ETB (EDNRB), the two receptors for EDN1. In the present work, we hypothesised that molecular variation in these genes could be a major determinant of the degree of bronchial obstruction. The purpose of this study was to investigate whether the genetic polymorphisms of preproET-1, EDNRA and EDNRB genes were associated with the degree of airway obstruction, assessed by FEV1.
Polymorphisms of preproET-1, EDNRA and EDNRB were first studied in a population of adult asthmatic patients. Results were confirmed in a large population of adults from the general population from the ECRHS II study.
In our population of adult asthmatic patients, the EDNRB-30G>A (Leu277Leu) polymorphism (GG genotype) is strongly associated with a low FEV1 and with a higher percentage of patients with FEV1 < 80% of predicted value. No relationship was found between pulmonary function and EDNRA-1363C>T (His323His) or preproET-1-595G>T (Lys198Asp) polymorphism. In the adult population from the ECRHS II, we found a similar association between GG genotype and a low FEV1 or a higher percentage of subjects with FEV1 < 80% predicted, especially in the subgroups of asthmatics subjects (OR = 4.31 (95%CI 1.03 - 18.04)) and smokers (OR = 7.42 (95%CI 1.69 - 32.6)).
the EDNRB-30G>A polymorphism could be a determinant of airway obstruction in humans with predisposing factors such as tobacco smoke exposure or asthma.
BMC Pulmonary Medicine 02/2007; 7:5. · 1.33 Impact Factor
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Camille Taillé,
Armelle Guénégou,
Abdelhamid Almolki,
Marie Piperaud,
Bénédicte Leynaert,
Sandrine Vuillaumier,
Françoise Neukirch,
Jorge Boczkowski,
Michel Aubier, Joëlle Benessiano,
Bruno Crestani
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ABSTRACT: Abstract
Background
Endothelin-1 (EDN1) has been involved in the development of airway obstruction and inflammation in asthma. Several polymorphisms have been identified among the genes encoding for preproET1, an inactive precursor of ET-1, and for ET<sub>A </sub>(EDNRA) and ET<sub>B </sub>(EDNRB), the two receptors for EDN1. In the present work, we hypothesised that molecular variation in these genes could be a major determinant of the degree of bronchial obstruction. The purpose of this study was to investigate whether the genetic polymorphisms of preproET-1 , EDNRA and EDNRB genes were associated with the degree of airway obstruction, assessed by FEV<sub>1</sub>.
Methods
Polymorphisms of preproET-1, EDNRA and EDN RB were first studied in a population of adult asthmatic patients. Results were confirmed in a large population of adults from the general population from the ECRHS II study.
Results
In our population of adult asthmatic patients, the EDNRB-30G>A (Leu277Leu) polymorphism (GG genotype) is strongly associated with a low FEV<sub>1 </sub>and with a higher percentage of patients with FEV1 < 80% of predicted value. No relationship was found between pulmonary function and EDNRA-1363C>T (His323His) or preproET-1-595G>T (Lys198Asp) polymorphism. In the adult population from the ECRHS II, we found a similar association between GG genotype and a low FEV<sub>1 </sub>or a higher percentage of subjects with FEV1 < 80% predicted, especially in the subgroups of asthmatics subjects (OR = 4.31 (95%CI 1.03 – 18.04)) and smokers (OR = 7.42 (95%CI 1.69 – 32.6)).
Conclusion
the EDNRB-30G>A polymorphism could be a determinant of airway obstruction in humans with predisposing factors such as tobacco smoke exposure or asthma.
BMC Pulmonary Medicine. 01/2007;
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ABSTRACT: A higher exposure to bacterial compounds is purported to explain the lower prevalence of allergy in farm children, but responsiveness to bacterial compounds is modulated by genetic factors.
To assess whether the protective effect of farm exposure on atopy is influenced by a CD14 promoter functional polymorphism.
We administered a detailed questionnaire on farm exposure in childhood and genotyped the CD14 C-159T polymorphism in 2 French centers participating in the European Community Respiratory Health Survey (ECRHS)-II.
Six hundred randomly selected young adults provided blood samples for IgE measurements and had CD14 C-159T genotyped. Exposure to a farming environment in early life was associated with a reduced risk of nasal allergies (odds ratio [OR], 0.54; 95% CI, 0.29-1.00) and atopic sensitization (OR, 0.47; 95% CI, 0.24-0.93) in adulthood. A lower risk of allergic rhinitis and atopy was also observed in carriers of the CD14-159TT genotype compared with -159CC subjects (OR, 0.52; 95% CI, 0.30-0.88; and OR, 0.54; 95% CI, 0.31-0.92, respectively). When farm exposure and CD14 C-159T were considered together, the risk of nasal allergies and atopy was the most reduced in the subjects who combined both an early-life exposure to a farming environment and the -159TT genotype (OR, 0.26; 95% CI, 0.07-0.94; and OR, 0.21; 95% CI, 0.05-0.93, respectively, vs nonexposed -159CC+CT subjects). The results were consistent in the 2 centers, supporting the validity of the results.
A gene-by-environment interaction between CD14 C-159T and environmental exposure in childhood may modify the development of atopy.
This polymorphism should be considered in interventions studies that use microbial stimuli to reduce sensitization.
Journal of Allergy and Clinical Immunology 10/2006; 118(3):658-65. · 11.00 Impact Factor
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Ziad Mallat,
Ph Gabriel Steg, Joëlle Benessiano,
Marie-Laure Tanguy,
Keith A Fox,
Jean-Philippe Collet,
Omar H Dabbous,
Patrick Henry,
Kathryn F Carruthers,
Anne Dauphin,
Carla Sibella Arguelles,
Joëlle Masliah,
Bénédicte Hugel,
Gilles Montalescot,
Jean-Marie Freyssinet,
Bernard Asselain,
Alain Tedgui
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ABSTRACT: The purpose of this study was to determine the prognostic value of circulating secretory phospholipase A2 (sPLA2) activity in patients with acute coronary syndromes (ACS).
The plasma level of type IIA sPLA2 is a risk factor for coronary artery disease (CAD) and is associated with adverse outcomes in patients with stable CAD. The prognostic impact of sPLA2 in patients with ACS is unknown.
Secretory phospholipase A2 antigen levels and activity were measured in plasma samples of 446 patients with ACS, obtained at the time of enrollment.
Baseline sPLA2 activity was associated with the risk of death and myocardial infarction (MI). The unadjusted rate of death and MI increased in a stepwise fashion with increasing tertiles of sPLA2 activity (p < 0.0001). The association remained significant in the subgroup of patients who had MI with ST-segment elevation (p = 0.014) and the subgroup of patients who had unstable angina or non-ST-segment elevation MI (p < 0.002). After adjustment for clinical and biological variables, the hazard ratios for the combined end point of death or MI in the third tertile of sPLA2 compared with the first and second tertiles was 3.08 (95% confidence interval, 1.37 to 6.91, p = 0.006).
A single measurement of plasma sPLA2 activity at the time of enrollment provides strong independent information to predict recurrent events in patients with ACS.
Journal of the American College of Cardiology 11/2005; 46(7):1249-57. · 14.16 Impact Factor
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ABSTRACT: A gene polymorphism of preproendothelin-1 (a G-to-T transversion that predicts a Lys/Asn change at codon 198) associated with an increased risk of hypertension has been recently described in patients carrying the T allele. No study has yet determined the impact of this polymorphism on vascular reactivity, although a functional role for endothelin-1 in the pathophysiology of hypertension has been clarified. At subthreshold concentrations, endothelin-1 and angiotensin II induce a potentiation of alpha-adrenergic-dependent vascular tone caused by an increased sensitivity of the contractile apparatus to calcium. We investigated phenylephrine-induced tone and its amplification by endothelin-1 and angiotensin II in human mammary artery rings in vitro. Contractions to phenylephrine (0.1 to 100 micromol) and endothelin-1 (0.1 to 300 nmol) were not significantly different in rings from GT/TT (n=27) and GG (n=21) patients. A subthreshold concentration of endothelin-1 (10 pmol) potentiated a phenylephrine-induced contraction (eg, 44 +/- 12% increase in tone with phenylephrine 1 micromol/L, P<0.001) that was significantly higher in the GT/TT group than in the GG group (eg, 44 +/- 12% versus 82 +/- 11%, P<0.01). A similar effect on response to phenylephrine was observed with a subthreshold concentration of angiotensin II. We also found a higher response to calcium in arteries from GT/TT patients. Endothelium-dependent or -independent relaxations were unaffected by the genotype. These data suggest that the preproendothelin-1 gene polymorphism is associated with a higher potentiating effect of endothelin-1 and angiotensin II, probably in relation with higher calcium sensitivity. These changes in vascular reactivity might help to understand the relations between this polymorphism and cardiovascular disorders.
Hypertension 03/2002; 39(2):209-13. · 6.21 Impact Factor
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ABSTRACT: Heme oxygenase (HO1) acts against oxidants which are thought to play a major role in the pathogenesis of chronic obstructive pulmonary disease (COPD). A (GT)n repeat polymorphism in the HO1 gene promoter can modulate the transcription of this gene in response to oxidative stress. We postulated that this polymorphism might be associated with the degree and decline of lung function in subjects exposed to oxidative stress (smokers). We genotyped 749 French subjects (20-44 years, 50% men, 40% never-smokers) who were examined in both 1992 and 2000 as part of the ECRHS. Lung function was assessed by measuring FEV1 (Forced Expiratory Volume in 1 second) and the FEV1/FVC (Forced Ventilatory Capacity) ratio. We compared long (L)-allele carriers ((GT)n > or = 33 repeats for one or two alleles) to non-carriers. During the 8-year study period, the mean annual FEV1 and FEV1/FVC declines were -30.9 +/- 31.1 ml/year and -1.8 +/- 6.1 units/year, respectively. The FEV1/FVC decline was steeper in L-allele carriers than in non-carriers (-2.6 +/- 5.5 vs -1.5 +/- 6.4, p = 0.07). There was a strong interaction between allele L and smoking. In 2000, allele L was associated with lower FEV1 and FEV1/FVC values in heavy smokers (J20 cig/day) only (p for the interactions, 0.07 and 0.002 respectively). Baseline heavy smokers carrying allele L showed the steepest FEV1 decline (-62.0 +/- 29.5 ml/year) and the steepest FEV1/FVC decline (-8.8 +/- 5.4 units/year) (p for the interactions, 0.009 and 0.0006). These results suggest that a long (L) HO1 gene promoter increases the risk of airway obstruction in heavy smokers.
Bulletin de l'Académie nationale de médecine 190(4-5):877-90; discussion 890-1. · 0.25 Impact Factor
