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Biomedical subjects

V Devauchelle

Publications and source records attributed to V Devauchelle.

17 recordsLinked to original sources
PubMed2006

Continuation of treatment with infliximab in ankylosing spondylitis: 2-yr open follow-up.

OBJECTIVE: To evaluate the continuation and safety of treatment with infliximab in ankylosing spondylitis (AS) over a 2-yr period. METHODS: This study was an open, observational, 2-yr extension study of an open-label study of three induction infusions of infliximab in refractory AS. The fourth infusion was performed only in case of relapse. Thereafter, infliximab was to be administered as needed according to the rheumatologist's opinion; however, for some patients, infusions were performed systematically. RESULTS: None of the 50 recruited patients was lost to follow-up. Thirteen patients (26%) interrupted their treatment by infliximab: four for inefficacy, seven for adverse events, of which four were for allergic reactions to the infusion, and two for other reasons. For all of the 46 patients who had had three infusions judged efficacious and well tolerated, a fourth infusion was performed because of a flare of the disease, after a mean interval of 20.3+/-9.9 weeks (range 7.3-57.9). Over the 24 months, the mean interval between infusions was 11.6+/-9.0 weeks. This interval was longer when patients were treated only as needed (mean 14.3+/-12.1 weeks) than systematically (mean 9.8+/-5.7 weeks). Side-effects were similar to those noted in shorter-term studies; seven patients suffered serious adverse events. There were no deaths, no malignancies and no tuberculosis. CONCLUSION: This study confirms the long-term treatment continuation of infliximab in AS, and shows an acceptable safety profile. It appears that for some patients the disease can be controlled with long intervals between infusions; these findings warrant further studies.

Adult↗
PubMed2006

Central and peripheral RAG protein re-expression: underestimate mechanisms of tolerance?

The generation of developing B cells in the bone marrow is regulated by recombination activating genes RAG1 and RAG2 proteins. They contribute to the synthesis of functional antibodies (Abs) that can present self-reactivities following V(D)J (V, variable; D, diversity and J, joining) recombination. The emergence of autoreactive B cells is prevented by deletion through apoptosis, by stimulation blockade through anergy, or by synthesis of a new B-cell receptor through receptor edition. In the periphery, somatic hypermutation during the course of germinal centre (GC) responses can lead to the appearance of autoreactive and low-affinity Ab-producing B cells. Apoptotic deletion and receptor revision regulate these autoreactive and inappropriate B cells. Moreover, the presence of RAG-positive B cells outside GCs suggest that still uncharacterized regulation checkpoint, associated with secondary V(D)J recombination, also contribute to the regulation of autoreactivities. Failure in central and/or peripheral tolerance mechanisms associated with RAG expression could contribute to the terminal differentiation of autoreactive B cells leading to autoimmune states.

Animals↗
PubMed2004

[What place for DNA microarray in inflammatory diseases?].

PURPOSE: DNA chip is a recently developed technique allowing analysis of thousands of genes at the same time in multiple biological samples. In few years it has become an obligatory step in massive gene expression study. The enormous quantity of results generated and the new way of thinking allowed make this kind of study a true revolution. KEY MESSAGE AND RECENT FACTS: The enormous discovery potential permitted by the accomplishment of multiple genomes sequencing and the advent of technologies allowing massive gene expression analyses have totally modified the diseases approach. Considering the obtainment of a real full picture of the transcriptional activity in an organ, tissue or cell is now legitimate. DNA microarray is obviously not the only technique allowing such type of analysis but it is without contest the technology which is the most popular and the one which has been recently the subject of the most important developments. It is certainly the technology which brought the main advances in tumour classification and discovery of new biomarkers. The first results based on this technology in inflammatory diseases have recently been reported. PERSPECTIVE AND PROJECTS: The optimal use of DNA microarrays will necessitate a powerful statistical analysis and an high quality biological experimentation. Strict standard and quality criteria are developing. Obviously, the DNA chips have a role to play in multifactorial inflammatory diseases mainly through their potential to bring new answers to diagnostic and pathophysiological problems. One potential development of the technique in such diseases will be the definition of disease specific gene profiles and the generation of chips allowing the detection of few targeted genes with all the known mutations of these genes. The correlation of global or targeted gene expression with clinical and pathological data will allow a new step forward in the understanding and taking care of inflammatory diseases.

Animals↗
PubMed2004

DNA microarray allows molecular profiling of rheumatoid arthritis and identification of pathophysiological targets.

This study was undertaken to evaluate the possibility to obtain a molecular signature of rheumatoid arthritis (RA) comparatively osteoarthritis (OA), and to lay the bases to develop new diagnostic tools and identify new targets. Microarray technology was used for such an analysis. The gene expression profiles of synovial tissues from patients with confirmed RA, and patients with OA were established and compared. A set of 63 genes was selected, based, more specifically, on their overexpression or underexpression in RA samples compared to OA. Results for six of these genes have been verified by quantitative PCR using both samples identical to those used in the microarray experiments and entirely separate samples. Expression profile of the 48 known genes allowed the correct classification of additional RA and OA patients. Furthermore, the distinct expression of three of the selected genes was also studied by quantitative RT-PCR in cultured synovial cells. Detailed analysis of the expression profile of the selected genes provided evidence for dysregulated biological pathways, pointed out to chromosomal location and revealed novel genes potentially involved in RA. It is proposed that such an approach allows valuable diagnosis/prognostics tools in RA to be established and potential targets for combating the disease to be identified.

Adult↗
PubMed2002

Efficacy of infliximab in refractory ankylosing spondylitis: results of a six-month open-label study.

OBJECTIVE: To evaluate the efficacy and safety of a loading regimen of the anti-tumour necrosis factor alpha (TNF-alpha) antibody infliximab in predominantly axial severe ankylosing spondylitis (AS). METHODS: We enrolled in this study 50 patients (76% males, 87% HLA-B27(+), median age 35 yr, median disease duration 13 yr) with active AS [Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) >or=30/100 and serum C-reactive protein concentration >or=15 mg/l) despite treatment with a non-steroidal anti-inflammatory drug, and without peripheral arthritis, uveitis or active inflammatory bowel disease. Other disease-modifying anti-rheumatic drugs were discontinued >or=3 months before inclusion and were not allowed during the study. Patients received three infusions of infliximab (5 mg/kg) at weeks 0, 2 and 6 and were monitored clinically and biologically until week 24. RESULTS: Forty-eight patients completed the treatment. In intention-to-treat analysis, all parameters were significantly improved at week 2 and generally reached maximal improvement at week 8. The proportion of responders, defined by a reduction of >or=20% in the global assessment of pain (GAP) or by the AS Assessment Study Group (ASAS 20%) criteria, and the proportion of patients reaching partial remission were 98, 94 and 70% respectively. Relapse, defined as >or=50% loss of maximal GAP improvement, occurred in 73% of completers, with a median delay of 14 weeks after the third infusion. No serious adverse event related to the treatment was observed. CONCLUSIONS: This study confirms, in a large group of severely affected AS patients, the remarkable efficacy of infliximab. Relapse usually occurred after discontinuation of the drug, but almost one-third of completers were still free of relapse 4 months after the last infusion.

Adult↗
PubMed2001

Ability of the American College of Rheumatology 1987 criteria to predict rheumatoid arthritis in patients with early arthritis and classification of these patients two years later.

OBJECTIVE: To determine how well the American College of Rheumatology (ACR; formerly, the American Rheumatism Association) 1987 classification criteria for rheumatoid arthritis (RA), when used at study inclusion in a cohort of 270 patients with early (<1 year) arthritis, predicted a diagnosis of RA 2 years later and how well they classified these patients at the end of the 2 years. METHODS: Patients were evaluated during 1995-1997 at 7 hospitals in the Brittany region of France. Patients were evaluated at 6-month intervals until November 1999. The diagnosis made by a panel of 5 rheumatologists (P5R) after the last visit was used as the "gold standard." The ACR 1987 criteria for RA were applied prospectively, without taking into account the initial diagnosis. RESULTS: At the last visit (mean +/- SD followup 29.1 +/- 11.8 months; median 30 months), the P5R diagnosed RA in 98 patients. At the last visit, classification by the ACR criteria was satisfactory, and the combination of an office-based rheumatologist's (OBR's) diagnosis of RA and fulfillment of the ACR criteria was sensitive (87%; 85 of 98 RA patients had both) and highly specific (99%; 170 of 172 non-RA patients did not have both). Application of the criteria at the first visit was of limited value for predicting a diagnosis of RA 2 years later. CONCLUSION: After a 2-year followup, the ACR 1987 classification criteria used in combination with an OBR's diagnosis were effective in distinguishing patients with and without RA. The criteria were not useful for predicting RA in patients with arthritis onset within the previous year. Some patients who met the criteria at baseline and after 2 years did not have RA, suggesting that incorporating exclusion criteria may improve the performance of the ACR criteria when used without taking into account the diagnosis by a rheumatologist, particularly in early arthritis.

Adolescent↗
PubMed2001

Is hypocomplementemia useful for diagnosing or predicting extra-articular manifestations in patients with rheumatoid arthritis?

OBJECTIVE: Serum CH50 and C4 levels are usually normal or elevated in rheumatoid arthritis (RA) but are classically decreased in patients with serious extra-articular manifestations (SEAMs) of the disease. The objective of this study was to evaluate whether complement assays are useful in diagnosing or predicting SEAMs of RA. METHODS: First, a cross-sectional study of 405 patients admitted for RA compared patients with and without hypocomplementemia. Then, a retrospective longitudinal design was used to investigate within-patient complement level variations overtime. RESULTS: In the univariate analysis, patients with low CH50 and C4 levels were more likely to have vasculitis and/or cryoglobulinemia than those with normal CH50 and C4 levels, and nodules were more common in the patients with low than with normal C4 levels. In a multivariate model based on symptoms, low C4 was associated with vasculitis and pleurisy and low CH50 with vasculitis. However, these associations were too weak to make CH50 and C4 determination useful for detecting SEAMs, and the within-subject variations in patients with SEAMs limited the predictive value of these assays. CONCLUSION: Hypocomplementemia is of limited usefulness for detecting or predicting SEAMs.

Adult↗
PubMed1999

Glycosylation of immunoglobulin A influences its receptor binding.

Immunoglobulin A (IgA), which is heavily glycosylated, interacts with a variety of receptors, e.g. the asialoglycoprotein receptor (ASGP-R), which binds terminal galactose residues, and the Fcalpha receptor (FcalphaRI). It has thus been proposed that elevated serum levels of IgA in primary Sjögren's syndrome (pSS) are caused by its defective clearance. To test this hypothesis, we developed a method (based on sialyl transferases eluted from a hepatoma cell line) to increase the amount of sialic acid (SA) on IgA, and used a battery of IgA1- and IgA2-specific glycosidases to reduce this amount. Binding of IgA1 and IgA2 to ASGP-R and FcalphaRI was found to be sugar dependent because oversialylated IgA bound less than native or desialylated IgA. However, individual sugars did not play a direct role in this binding. Given that IgA are oversialylated in pSS, defective clearance of IgA may indeed be ascribed to an excess of SA in IgA1 and IgA2.

Acetylgalactosamine↗
PubMed1999

Are tennis players at increased risk for low back pain and sciatica?

OBJECTIVE: Tennis practiced intensively is generally held to be a risk factor for low back pain. The objective of our study was to evaluate the prevalence of low back pain with or without sciatica during the last week in tennis players versus controls. PATIENTS AND METHODS: During an international tennis competition held in Brest, France, ten physicians or medical students interviewed 633 spectators older than 18 years and divided them into tennis players and controls. The sample size was selected to allow detection of a twofold increase in the risk of low back pain in tennis players (with alpha = 5% and 1-beta = 80%). RESULTS: Of the 633 subjects, 388 were and 245 were not tennis players. There were 421 men with a mean age of 37 +/- 13.7 years and 212 women with a mean age of 34.3 +/- 12.7. Among the men, 49 of the 281 tennis players (17.4%) reported low back pain during the last week versus 26 of the 140 controls (18.6%). Corresponding figures in women were 20 of 107 tennis players (18.7%) and 29 of 105 controls (27.6%). Sciatica was not more common in tennis players (men, 20 of 281 tennis players [7.1%] versus 6 of 140 controls [4.3%]; women, 8 of 107 tennis players [7.5%] versus 10 of 105 controls [9.5%]). None of the differences between tennis players and controls were significant. The number of hours spent playing tennis per week was similar in tennis players with and without low back pain. CONCLUSION: Our interview-based cross-sectional study found no evidence that playing tennis involves a higher risk of low back pain with or without sciatica.

Adolescent↗
PubMed1999

Prevalence of rheumatoid arthritis and spondyloarthropathy in Brittany, France. Société de Rhumatologie de l'Ouest.

OBJECTIVE: To document the prevalence of rheumatoid arthritis (RA) and spondyloarthropathy (SpA) in Brittany, France. METHODS: (1) Members of rheumatism self-help groups screened cases using questionnaires. (2) Rheumatologists in our unit contacted persons who had possible inflammatory rheumatic diseases and persons who refused the first interview. (3) When diagnosis remained unknown or discordant with the questionnaire, the general practitioner or the rheumatologist of these patients was interviewed. (4) Patients without diagnosis and who had not had a rheumatological examination were examined without charge by a rheumatologist. RESULTS: An overall prevalence rate of 0.62% (0.33-0.91) and 0.47% (0.22-0.72) was found for RA and for SpA, respectively. The prevalence of RA and SpA was 0.86 (0.39-1.33) and 0.53 (0.16-0.9) in women and 0.32 (0.01-0.63) and 0.41 (0.05-0.77) in men. The minimum prevalence of RA and SpA calculated on the estimated initial group (3189 persons) was 0.53 (0.28-0.78) and 0.41 (0.18-0.63), respectively. CONCLUSION: Our telephone survey revealed that the prevalences of RA and SpA are nearly similar among our population and that SpA is as common in women as in men.

Adolescent↗
PubMed1998

Changes in glycosylation of immunoglobulins in primary Sjögren's syndrome.

Serum IgG and IgA are glycoprotein and significant glycoform abnormalities have been established in primary Sjögren's syndrome. The proportion of asialylated IgG is abnormally high in the patients, whereas IgA1 and IgA2 appear to be over-sialylated. This peculiarity might explain the defective binding of IgA to asialoglycoreceptors. Furthermore, the activity of alpha 2,6 sialyl transferase is higher in the IgA-producing B cells from the patients than in the controls, whereas the alpha 2,3 sialyl transferase operates in the former cells but not in the latter. The mechanism of this enzyme dysregulation warrants elucidation.

B-Lymphocytes↗
PubMed1997

[Diagnostic value of the HLA phenotype in inflammatory rheumatic diseases].

OBJECTIVES: HLA phenotyping is usually considered as costly and unnecessary for the diagnosis of inflammatory rheumatoid diseases. The aim of our work was to assess the diagnostic value of HLA phenotyping compared with the diagnostic value of sex and age at the onset of disease in cases where there is a doubt between rheumatoid polyarthritis and spondyloarthropathy with peripheral involvement. METHODS: The relative prevalence of inflammatory rheumatoid diseases was calculated for 138 patients hospitalized for diagnosis of rheumatoid disease. We considered however that in these patients the etiology of the inflammatory rheumatoid disease with synovitis, after search for etiology, could be either spondyloarthropathy with peripheral involvement or early-stage rheumatoid polyarthritis. Positive and negative predictive values were calculated by comparison between these two diseases. The sensitivity of HLA B27 in spondyloarthropathy with peripheral involvement was determined in a population of 83 hospitalized patients with confirmed diagnosis. The prevalence of HLA DR4 in rheumatoid polyarthritis was determined in 375 hospitalized patients with confirmed diagnosis. Predictive values were calculated using Bayes formula. RESULTS: The analysis of the positive and negative predictive values for HLA B27 showed that the diagnostic value of this allele was much greater than age at disease onset and sex in spondyloarthropathy with peripheral involvement. For rheumatoid arthritis, comparison of the diagnostic value of HLA DR4 versus age at disease onset and sex showed the lower performance of HLA DR4. However, the positive predictive value of HLA DR4 in rheumatoid polyarthritis was similar to that for these factors and equivalent to that of HLA B27. The positive predictive value for the combinations HLA DR4+ HLA B27- and HLA B27+ HLA DR4- was 0.90 for rheumatoid polyarthritis and spondyloarthropathy with peripheral involvement respectively. CONCLUSION: The validity of these promising findings should be confirmed in prospective studies.

Age Factors↗
PubMed1997

Prevalence of symptomatic bronchiectasis in patients with rheumatoid arthritis.

OBJECTIVE: To evaluate the prevalence of symptomatic bronchiectasis in patients with rheumatoid arthritis. METHODS: Cross-sectional retrospective study of 453 rheumatoid arthritis patients. All patients completed a questionnaire designed to detect manifestations of bronchiectasis and had a chest film taken. Computed tomography of the chest was performed in those patients whose chest film was normal. RESULTS: Thirteen patients (2.9%), all female, had symptoms that met Walker's criteria for definite (n = 7) or probable (n = 6) bronchiectasis. Symptom onset was during childhood or adolescence in 69% of cases and antedated the first symptoms of rheumatoid arthritis in all patients but one. Six of the 13 patients (46%) had chest film abnormalities suggestive of bronchiectasis, and three of the remaining seven patients had abnormal computed tomography findings, yielding a total of nine cases of bronchiectasis confirmed by imaging studies among the 13 patients with suggestive symptoms (69%). This proportion rose to 90% when the three patients who failed to come to their computed tomography appointment were excluded. CONCLUSION: Using a methodological approach similar to that previously used by pneumologists, we found a 2.9% prevalence of symptomatic bronchiectasis in a population of hospitalized rheumatoid arthritis patients, which is higher than the 0.03% prevalence previously reported in the population at large.

Adolescent↗