Deep resequencing of GWAS loci identifies independent rare variants associated with inflammatory bowel disease.
; ; et al
in Nature Genetics (2012), 43(11), 1066-73
More than 1,000 susceptibility loci have been identified through genome-wide association studies (GWAS) of common variants; however, the specific genes and full allelic spectrum of causal variants ... [more ▼]
More than 1,000 susceptibility loci have been identified through genome-wide association studies (GWAS) of common variants; however, the specific genes and full allelic spectrum of causal variants underlying these findings have not yet been defined. Here we used pooled next-generation sequencing to study 56 genes from regions associated with Crohn's disease in 350 cases and 350 controls. Through follow-up genotyping of 70 rare and low-frequency protein-altering variants in nine independent case-control series (16,054 Crohn's disease cases, 12,153 ulcerative colitis cases and 17,575 healthy controls), we identified four additional independent risk factors in NOD2, two additional protective variants in IL23R, a highly significant association with a protective splice variant in CARD9 (P < 1 x 10(-16), odds ratio approximately 0.29) and additional associations with coding variants in IL18RAP, CUL2, C1orf106, PTPN22 and MUC19. We extend the results of successful GWAS by identifying new, rare and probably functional variants that could aid functional experiments and predictive models. [less ▲]Detailed reference viewed: 28 (1 ULg)
Does co-treatment with immunosuppressors improve outcome in patients with Crohn's disease treated with adalimumab?
; LOUIS, Edouard ; Belaiche, Jacques et al
in Alimentary Pharmacology & Therapeutics (2012), 36(11-12), 1040-8
BACKGROUND: There is clear benefit from combination therapy with infliximab and immunosuppressive drugs (IS), but few data are available for adalimumab (ADA). AIM: To assess the efficacy of ADA ... [more ▼]
BACKGROUND: There is clear benefit from combination therapy with infliximab and immunosuppressive drugs (IS), but few data are available for adalimumab (ADA). AIM: To assess the efficacy of ADA monotherapy and ADA+IS for induction and maintenance therapy in Crohn's disease. METHODS: Retrospective study of patients with Crohn's disease treated with ADA in Oxford, UK or Liege, Belgium. Treatment periods were divided into 6-month semesters. A combination therapy semester was defined as ADA+IS for at least 3 months; successful induction meant clinical response; a semester with flare as ADA dose escalation, starting steroids, perianal complication, or surgery; and ADA failure as ADA withdrawal for secondary loss of response or intolerance. Semesters with and without flares were compared through univariate and multivariate analysis. RESULTS: Successful induction was achieved in 171/207 (83%) patients, with no significant difference between ADA+IS and ADA monotherapy (85% vs. 82%, P = 0.50). Five hundred and sixty-two semesters in 181 patients were included for maintenance analysis. ADA+IS was not associated with fewer semesters with flare (34% vs. 35%, P = 0.96), or with ADA failure (6% vs. 8%, P = 0.43). Nevertheless, combination therapy in the first semester was associated with a lower risk of ADA failure (5% vs. 10%, P = 0.04, OR = 0.48) and combination therapy beyond 6 months was associated with fewer semesters with flares (14% vs. 36%, P = 0.02, OR = 0.31). CONCLUSIONS: There may be a benefit from adalimumab+immunosuppressive drugs combination therapy during the first semester of initiating adalimumab, with a slight decrease in adalimumab failure and lower need for adalimumab dosage escalation. [less ▲]Detailed reference viewed: 29 (1 ULg)
Genetique et environnement dans les maladies inflammatoires chroniques de l'intestin.
Louis, Edouard ; VAN KEMSEKE, Catherine ; LATOUR, Pascale et al
in Revue Médicale de Liège (2012), 67(5-6), 298-304
Inflammatory bowel diseases are both environmental and genetic illnesses. More than one hundred genes or loci involved in the regulation of innate or acquired immune response as well as intestinal mucosa ... [more ▼]
Inflammatory bowel diseases are both environmental and genetic illnesses. More than one hundred genes or loci involved in the regulation of innate or acquired immune response as well as intestinal mucosa homeostasis have been identified. Environmental studies have been less numerous up to now and only smoking and appendectomy have been validated, as protector for ulcerative colitis, while smoking is clearly associated with an increased risk and more severe forms of Crohn's disease. An important role is also currently suspected for the intestinal flora and the dysbiosis described in inflammatory bowel disease could contribute to the triggering or the persistence of the inflammation. New therapeutic strategies are currently studied, particularly aiming at targeting immune, inflammatory or homeostatic pathways corresponding to the predisposing gene variants. [less ▲]Detailed reference viewed: 78 (6 ULg)
Development of the paris definition of early Crohn's disease for disease-modification trials: results of an international expert opinion process.
; ; et al
in American Journal of Gastroenterology (2012), 107(12), 1770-6
We report the findings and outputs of an international expert opinion process to develop a definition of early Crohn's disease (CD) that could be used in future disease-modification trials. Nineteen ... [more ▼]
We report the findings and outputs of an international expert opinion process to develop a definition of early Crohn's disease (CD) that could be used in future disease-modification trials. Nineteen experts on inflammatory bowel diseases held an international expert opinion meeting to discuss and agree on a definition for early CD to be used in disease-modification trials. The process included literature searches for the relevant basic-science and clinical evidence. A published preliminary definition of early CD was used as the basis for development of a proposed definition that was discussed at the expert opinion meeting. The participants then derived a final definition, based on best current knowledge, that it is hoped will be of practical use in disease-modification trials in CD. [less ▲]Detailed reference viewed: 35 (3 ULg)
Maintenance of Remission Among Patients With Crohn's Disease on Antimetabolite Therapy After Infliximab Therapy Is Stopped.
Louis, Edouard ; ; et al
in Gastroenterology (2012), 142(1), 63-70531
BACKGROUND & AIMS: It is important to determine whether infliximab therapy can be safely interrupted in patients with Crohn's disease who have undergone a period of prolonged remission. We assessed the ... [more ▼]
BACKGROUND & AIMS: It is important to determine whether infliximab therapy can be safely interrupted in patients with Crohn's disease who have undergone a period of prolonged remission. We assessed the risk of relapse after infliximab therapy was discontinued in patients on combined maintenance therapy with antimetabolites and identified factors associated with relapse. METHODS: We performed a prospective study of 115 patients with Crohn's disease who were treated for at least 1 year with scheduled infliximab and an antimetabolite and had been in corticosteroid-free remission for at least 6 months. Infliximab was stopped, and patients were followed up for at least 1 year. We associated demographic, clinical, and biologic factors with time to relapse using a Cox model. RESULTS: After a median follow-up period of 28 months, 52 of the 115 patients experienced a relapse; the 1-year relapse rate was 43.9% +/- 5.0%. Based on multivariable analysis, risk factors for relapse included male sex, the absence of surgical resection, leukocyte counts >6.0 x 10(9)/L, and levels of hemoglobin </=145 g/L, C-reactive protein >/=5.0 mg/L, and fecal calprotectin >/=300 mug/g. Patients with no more than 2 of these risk factors (approximately 29% of the study population) had a 15% risk of relapse within 1 year. Re-treatment with infliximab was effective and well tolerated in 88% of patients who experienced a relapse. CONCLUSIONS: Approximately 50% of patients with Crohn's disease who were treated for at least 1 year with infliximab and an antimetabolite agent experienced a relapse within 1 year after discontinuation of infliximab. However, patients with a low risk of relapse can be identified using a combination of clinical and biologic markers. [less ▲]Detailed reference viewed: 24 (4 ULg)
Auto-immune gastritis characteristics in a large series of patients with auto-immune thyroiditis.
VALDES SOCIN, Hernan Gonzalo ; ; LUTTERI, Laurence et al
in XXIVth Belgian Week of Gastroenterology 2012 - Abstract book (2012)Detailed reference viewed: 42 (7 ULg)
Rheumatoid arthritis and pregnancy: evolution of disease activity and pathophysiological considerations for drug use
; ; Geenen, Vincent et al
in Rheumatology (2011)
It has long been known that pregnancy and childbirth have a profound effect on the disease activity of rheumatic diseases. For clinicians, the management of patients with RA wishing to become pregnant ... [more ▼]
It has long been known that pregnancy and childbirth have a profound effect on the disease activity of rheumatic diseases. For clinicians, the management of patients with RA wishing to become pregnant involves the challenge of keeping disease activity under control and adequately adapting drug therapy during pregnancy and post-partum. This article aims to summarize the current evidence on the evolution of RA disease activity during and after pregnancy and the use of anti-rheumatic drugs around this period. Of recent interest is the potential use of anti-TNF compounds in the preconception period and during pregnancy. Accumulating experience with anti-TNF therapy in other immune-mediated inflammatory diseases, such as Crohn’s disease, provides useful insights for the use of TNF blockade in pregnant women with RA, or RA patients wishing to become pregnant. [less ▲]Detailed reference viewed: 68 (3 ULg)
Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47.
; ; et al
in Nature Genetics (2011), 43(3), 246-52
Genome-wide association studies and candidate gene studies in ulcerative colitis have identified 18 susceptibility loci. We conducted a meta-analysis of six ulcerative colitis genome-wide association ... [more ▼]
Genome-wide association studies and candidate gene studies in ulcerative colitis have identified 18 susceptibility loci. We conducted a meta-analysis of six ulcerative colitis genome-wide association study datasets, comprising 6,687 cases and 19,718 controls, and followed up the top association signals in 9,628 cases and 12,917 controls. We identified 29 additional risk loci (P < 5 x 10(-8)), increasing the number of ulcerative colitis-associated loci to 47. After annotating associated regions using GRAIL, expression quantitative trait loci data and correlations with non-synonymous SNPs, we identified many candidate genes that provide potentially important insights into disease pathogenesis, including IL1R2, IL8RA-IL8RB, IL7R, IL12B, DAP, PRDM1, JAK2, IRF5, GNA12 and LSP1. The total number of confirmed inflammatory bowel disease risk loci is now 99, including a minimum of 28 shared association signals between Crohn's disease and ulcerative colitis. [less ▲]Detailed reference viewed: 23 (7 ULg)
Laparoscopic antireflux surgery vs esomeprazole treatment for chronic GERD: the LOTUS randomized clinical trial.
; ; et al
in JAMA : Journal of the American Medical Association (2011), 305(19), 1969-77
CONTEXT: Gastroesophageal reflux disease (GERD) is a chronic, relapsing disease with symptoms that have negative effects on daily life. Two treatment options are long-term medication or surgery. OBJECTIVE ... [more ▼]
CONTEXT: Gastroesophageal reflux disease (GERD) is a chronic, relapsing disease with symptoms that have negative effects on daily life. Two treatment options are long-term medication or surgery. OBJECTIVE: To evaluate optimized esomeprazole therapy vs standardized laparoscopic antireflux surgery (LARS) in patients with GERD. DESIGN, SETTING, AND PARTICIPANTS: The LOTUS trial, a 5-year exploratory randomized, open, parallel-group trial conducted in academic hospitals in 11 European countries between October 2001 and April 2009 among 554 patients with well-established chronic GERD who initially responded to acid suppression. A total of 372 patients (esomeprazole, n = 192; LARS, n = 180) completed 5-year follow-up. Interventions Two hundred sixty-six patients were randomly assigned to receive esomeprazole, 20 to 40 mg/d, allowing for dose adjustments; 288 were randomly assigned to undergo LARS, of whom 248 actually underwent the operation. MAIN OUTCOME MEASURE: Time to treatment failure (for LARS, defined as need for acid suppressive therapy; for esomeprazole, inadequate symptom control after dose adjustment), expressed as estimated remission rates and analyzed using the Kaplan-Meier method. RESULTS: Estimated remission rates at 5 years were 92% (95% confidence interval [CI], 89%-96%) in the esomeprazole group and 85% (95% CI, 81%-90%) in the LARS group (log-rank P = .048). The difference between groups was no longer statistically significant following best-case scenario modeling of the effects of study dropout. The prevalence and severity of symptoms at 5 years in the esomeprazole and LARS groups, respectively, were 16% and 8% for heartburn (P = .14), 13% and 2% for acid regurgitation (P < .001), 5% and 11% for dysphagia (P < .001), 28% and 40% for bloating (P < .001), and 40% and 57% for flatulence (P < .001). Mortality during the study was low (4 deaths in the esomeprazole group and 1 death in the LARS group) and not attributed to treatment, and the percentages of patients reporting serious adverse events were similar in the esomeprazole group (24.1%) and in the LARS group (28.6%). CONCLUSION: This multicenter clinical trial demonstrated that with contemporary antireflux therapy for GERD, either by drug-induced acid suppression with esomeprazole or by LARS, most patients achieve and remain in remission at 5 years. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00251927. [less ▲]Detailed reference viewed: 28 (1 ULg)
The efficacy of shortening the dosing interval to once every six weeks in Crohn's patients losing response to maintenance dose of infliximab.
; ; et al
in Alimentary Pharmacology & Therapeutics (2011), 33(3), 349-57
Background Patients treated with infliximab for Crohn's disease (CD) frequently require intensified dosage due to loss of response. There are scant data regarding the efficacy of shortening the dosing ... [more ▼]
Background Patients treated with infliximab for Crohn's disease (CD) frequently require intensified dosage due to loss of response. There are scant data regarding the efficacy of shortening the dosing interval to 6 weeks. Aim We sought to investigate the efficacy of a once every 6 weeks' strategy compared with dose-doubling. Methods This work was a multicentre retrospective study of infliximab-treated CD patients who required dose escalation. The clinical outcome of patients treated by intensification to 5 mg/kg/6 weeks (6-week group) was compared with the outcome of patients whose infliximab was double-dosed (10 mg/kg/8 weeks or 5 mg/kg/4 weeks). Results Ninety-four patients (mean age: 29.8 years) were included in the study, 55 (59%) in the 6-week group and 39 (41%) in the double-dose group. Demographics and disease characteristics were similar between the two groups, although patients with re-emerging symptoms 5-7 weeks postinfusion were more likely to receive 5 mg/kg/6 weeks dosing (OR: 3.4, 95% CI: 1.4-8.8, P < 0.01). Early response to dose-intensification occurred in 69% of patients in the 6-week group and 67% in the double-dose group (P = N.S.). Regained response was maintained for 12 months in 40% compared with 29% of the patients respectively (P = N.S.). Conclusion In CD patients who lost response to standard infliximab dose, especially when symptoms re-emerge 5-7 weeks postinfusion, shortening the dosing interval to 6 weeks appears to be at least as effective as doubling the dose to 10 mg/kg or halving the infusion intervals to once in 4 weeks. [less ▲]Detailed reference viewed: 23 (6 ULg)
Resequencing of positional candidates identifies low frequency IL23R coding variants protecting against inflammatory bowel disease.
Momozawa, Yukihide ; Mni, Myriam ; Nakamura, Kayo et al
in Nature Genetics (2011), 43(1), 43-7
Genome-wide association studies (GWAS) have identified dozens of risk loci for many complex disorders, including Crohn's disease. However, common disease-associated SNPs explain at most approximately 20 ... [more ▼]
Genome-wide association studies (GWAS) have identified dozens of risk loci for many complex disorders, including Crohn's disease. However, common disease-associated SNPs explain at most approximately 20% of the genetic variance for Crohn's disease. Several factors may account for this unexplained heritability, including rare risk variants not adequately tagged thus far in GWAS. That rare susceptibility variants indeed contribute to variation in multifactorial phenotypes has been demonstrated for colorectal cancer, plasma high-density lipoprotein cholesterol levels, blood pressure, type 1 diabetes, hypertriglyceridemia and, in the case of Crohn's disease, for NOD2 (refs. 14,15). Here we describe the use of high-throughput resequencing of DNA pools to search for rare coding variants influencing susceptibility to Crohn's disease in 63 GWAS-identified positional candidate genes. We identify low frequency coding variants conferring protection against inflammatory bowel disease in IL23R, but we conclude that rare coding variants in positional candidates do not make a large contribution to inherited predisposition to Crohn's disease. [less ▲]Detailed reference viewed: 90 (31 ULg)
Thiopurine metabolites and TPMT activity measurement in inflammatory bowel disease.
in Alimentary Pharmacology & Therapeutics (2011), 34(9), 1138-9Detailed reference viewed: 10 (1 ULg)
Results of the 2nd part Scientific Workshop of the ECCO. II: Measures and markers of prediction to achieve, detect, and monitor intestinal healing in inflammatory bowel disease.
; ; et al
in Journal of Crohn's & colitis (2011), 5(5), 484-98
The healing of the intestine is becoming an important objective in the management of inflammatory bowel diseases. It is associated with improved disease outcome. Therefore the assessment of this healing ... [more ▼]
The healing of the intestine is becoming an important objective in the management of inflammatory bowel diseases. It is associated with improved disease outcome. Therefore the assessment of this healing both in clinical studies and routine practice is a key issue. Endoscopy for the colon and terminal ileum and computerized tomography or magnetic resonance imaging for the small bowel are the most direct ways to evaluate intestinal healing. However, there are many unsolved questions about the definition and the precise assessment of intestinal healing using these endoscopic and imaging techniques. Furthermore, these are relatively invasive and expensive procedures that may be inadequate for regular patients' monitoring. Therefore, biomarkers such as C-reactive protein and fecal calprotectin have been proposed as surrogate markers for intestinal healing. Nevertheless, the sensitivity and specificity of these markers for the prediction of healing may be insufficient for routine practice. New stool, blood or intestinal biomarkers are currently studied and may improve our ability to monitor intestinal healing in the future. [less ▲]Detailed reference viewed: 67 (1 ULg)
Necessity of phenotypic classification of inflammatory bowel disease.
Louis, Edouard ; VAN KEMSEKE, Catherine ; Reenaers, Catherine
in Best practice & research. Clinical gastroenterology (2011), 25 Suppl 1
Inflammatory bowel diseases (IBD) are classically divided in Crohn's disease (CD) and ulcerative colitis (UC). However, these two entities are still heterogeneous and a further classification in ... [more ▼]
Inflammatory bowel diseases (IBD) are classically divided in Crohn's disease (CD) and ulcerative colitis (UC). However, these two entities are still heterogeneous and a further classification in subphenotypes is necessary. Clinical subphenotypes are easy to use, do not necessitate complicated tests and can already give very important information for the management of the patients. In CD, clinical subphenotypes are based on age at diagnosis, disease location and disease behaviour. Age at diagnosis allows to differentiating paediatric CD, classical young adult onset and more seldom CD of the elderly. These categories are associated with a different risk of development of complications and disabling disease and may have partly different pathophysiology. The classification on disease behaviour, including stricturin, penetrating or uncomplicated disease may have an impact on reponse to medical treatment and need for surgery. Finally the classification based on location is particularly relevant since it has been associated with different types of complications. Particularly ileal disease has been associated with the risk of surgery and colonic (particularly rectal) disease, with the risk of perianal disease. In UC, the classification in subphenotypes is essentially based on disease location, distinguishing proctitis, left-sided colitis and extensive colitis. This subclassification also has a very significant clinical relevance since extensive colitis has been associated with and increased risk of colon cancer, colectomy and even in some studies, mortality. [less ▲]Detailed reference viewed: 33 (2 ULg)
Effect of adalimumab on work productivity and indirect costs in moderate to severe Crohn's disease: a meta-analysis.
; Louis, Edouard ; et al
in Canadian journal of gastroenterology = Journal canadien de gastroenterologie (2011), 25(9), 492-6
OBJECTIVE: To assess the effect of adalimumab on work productivity and indirect costs in patients with Crohn's disease (CD) using a meta-analysis of clinical trials. METHODS: Study-level results were ... [more ▼]
OBJECTIVE: To assess the effect of adalimumab on work productivity and indirect costs in patients with Crohn's disease (CD) using a meta-analysis of clinical trials. METHODS: Study-level results were pooled from all clinical trials of adalimumab for moderate to severe CD in which work productivity outcomes were evaluated. Work Productivity and Activity Impairment Questionnaire outcomes (absenteeism, presenteeism and total work productivity impairment [TWPI]) were extracted from adalimumab trials. Meta-analyses were used to estimate pooled averages and 95% CIs of one-year accumulated reductions in work productivity impairment with adalimumab. Pooled averages were multiplied by the 2008 United States national average annual salary ($44,101) to estimate per-patient indirect cost savings during the year following adalimumab initiation. RESULTS: The four included trials (ACCESS, CARE, CHOICE and EXTEND) represented a total of 1202 employed adalimumab-treated patients at baseline. Each study followed patients for a minimum of 20 weeks. Pooled estimates (95% CIs) of one-year accumulated work productivity improvements were as follows: -9% (-10% to -7%) for absenteeism; -22% (-26% to -18%) for presenteeism; and -25% (-30% to -20%) for TWPI. Reductions in absenteeism and TWPI translated into per-patient indirect cost savings (95% CI) of $3,856 ($3,183 to $4,529) and $10,964 ($8,833 to $13,096), respectively. CONCLUSION: Adalimumab provided clinically meaningful improvements in work productivity among patients with moderate to severe CD, which may translate into substantial indirect cost savings from an employer's perspective. [less ▲]Detailed reference viewed: 16 (0 ULg)
Evolution and predictive factors of relapse in ulcerative colitis patients treated with mesalazine after a first course of corticosteroids.
; Belaiche, Jacques ; Louis, Edouard et al
in Journal of Crohn's & colitis (2011), 5(3), 196-202
INTRODUCTION: Mesalazine remains the first line treatment for the induction and the maintenance of remission in mild to moderate ulcerative colitis (UC). Its efficacy as a maintenance treatment after a ... [more ▼]
INTRODUCTION: Mesalazine remains the first line treatment for the induction and the maintenance of remission in mild to moderate ulcerative colitis (UC). Its efficacy as a maintenance treatment after a first flare treated with corticosteroids has not been specifically studied. The aims of our work were to study a cohort of UC patients treated with mesalazine after a course of oral systemic corticosteroids and to identify predictive factors of relapse and of colectomy. MATERIAL AND METHOD: We studied retrospectively a cohort of 143 UC patients, who never received immunosuppressive drugs, and treated for the first time with oral corticosteroids for a flare. Among patients responding to corticosteroids, we studied the group treated by mesalazine after the flare. RESULTS: Fifty% (n=52) achieved a complete clinical remission with steroid weaning. In this group, 67% (n=35) received oral mesalazine. Seventy-five % of patients treated by mesalazine relapsed (median 29 months, range: 1-156). Fourteen % required a colectomy (median 11 months, range: 1-24). Kaplan Meier curve showed a relapse rate and a colectomy rate over one year of 26% and 11% respectively. In multivariate analysis, male gender and short duration of disease were predictive factors of the time-to-relapse. No factor was predictive of time-to-colectomy. CONCLUSION: Maintenance efficacy of mesalazine over one year after a first course of corticosteroids for a disease flare is reasonably high. The longer-term relapse rate becomes higher in male patients with a short disease duration. An immunosuppressive treatment could be discussed in case of further relapse despite improved medication-adherence. Medication-adherence should first be assessed and promoted. An immunosuppressive treatment could be discussed in case of further relapse despite improved medication-adherence. [less ▲]Detailed reference viewed: 23 (1 ULg)
Development of the Crohn's disease digestive damage score, the Lemann score.
; ; et al
in Inflammatory Bowel Diseases (2011), 17(6), 1415-22
Crohn's disease (CD) is a chronic progressive destructive disease. Currently available instruments measure disease activity at a specific point in time. An instrument to measure cumulative structural ... [more ▼]
Crohn's disease (CD) is a chronic progressive destructive disease. Currently available instruments measure disease activity at a specific point in time. An instrument to measure cumulative structural damage to the bowel, which may predict long-term disability, is needed. The aim of this article is to outline the methods to develop an instrument that can measure cumulative bowel damage. The project is being conducted by the International Program to develop New Indexes in Crohn's disease (IPNIC) group. This instrument, called the Crohn's Disease Digestive Damage Score (the Lemann score), should take into account damage location, severity, extent, progression, and reversibility, as measured by diagnostic imaging modalities and the history of surgical resection. It should not be "diagnostic modality driven": for each lesion and location, a modality appropriate for the anatomic site (for example: computed tomography or magnetic resonance imaging enterography, and colonoscopy) will be used. A total of 24 centers from 15 countries will be involved in a cross-sectional study, which will include up to 240 patients with stratification according to disease location and duration. At least 120 additional patients will be included in the study to validate the score. The Lemann score is expected to be able to portray a patient's disease course on a double-axis graph, with time as the x-axis, bowel damage severity as the y-axis, and the slope of the line connecting data points as a measure of disease progression. This instrument could be used to assess the effect of various medical therapies on the progression of bowel damage. [less ▲]Detailed reference viewed: 56 (2 ULg)
Discovery and biochemical characterisation of four novel biomarkers for osteoarthritis.
DE SENY, Dominique ; ; Fillet, Marianne et al
in Annals of the Rheumatic Diseases (2011), 70(6), 1144-52
OBJECTIVE: Knee osteoarthritis (OA) is a heterogeneous, complex joint pathology of unknown aetiology. Biomarkers have been widely used to investigate OA but currently available biomarkers lack specificity ... [more ▼]
OBJECTIVE: Knee osteoarthritis (OA) is a heterogeneous, complex joint pathology of unknown aetiology. Biomarkers have been widely used to investigate OA but currently available biomarkers lack specificity and sensitivity. Therefore, novel biomarkers are needed to better understand the pathophysiological processes of OA initiation and progression. METHODS: Surface enhanced laser desorption/ionisation-time of flight-mass spectrometry proteomic technique was used to analyse protein expression levels in 284 serum samples from patients with knee OA classified according to Kellgren and Lawrence (K&L) score (0-4). OA serum samples were also compared to serum samples provided by healthy individuals (negative control subjects; NC; n=36) and rheumatoid arthritis (RA) patients (n=25). Proteins that gave similar signal in all K&L groups of OA patients were ignored, whereas proteins with increased or decreased levels of expression were selected for further studies. RESULTS: Two proteins were found to be expressed at higher levels in sera of OA patients at all four K&L scores compared to NC and RA, and were identified as V65 vitronectin fragment and C3fpeptide. Of the two remaining proteins, one showed increased expression (unknown protein at m/z of 3762) and the other (identified as connective tissue-activating peptide III protein) was decreased in K&L scores >2 subsets compared to NC, RA and K&L scores 0 or 1 subsets. CONCLUSION: The authors detected four unexpected biomarkers (V65 vitronectin fragment, C3f peptide, CTAP-III and m/z 3762 protein) that could be relevant in the pathophysiological process of OA as having significant correlation with parameters reflecting local inflammation and bone remodelling, as well as decrease in cartilage turnover. [less ▲]Detailed reference viewed: 50 (21 ULg)
Prevalence and prediction of gastric mucosal abnormalities in a prospective series of 50 patients with graves-Basedow disease
VALDES SOCIN, Hernan Gonzalo ; ; LUTTERI, Laurence et al
Poster (2011)Detailed reference viewed: 32 (1 ULg)
Natalizumab to kill two birds with one stone: A case of celiac disease and multiple sclerosis.
Phan-Ba, Rémy ; LAMBINET, Nadine ; Louis, Edouard et al
in Inflammatory Bowel Diseases (2011), 17(6), 62-63Detailed reference viewed: 43 (16 ULg)