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Biomedical subjects

E Toussirot

Publications and source records attributed to E Toussirot.

At least 19 recordsLinked to original sources
PubMed2001

Influence of shared epitope-negative HLA-DRB1 alleles on genetic susceptibility to rheumatoid arthritis.

OBJECTIVE: Most patients with rheumatoid arthritis (RA) express the shared epitope (SE). It is not known whether SE-negative HLA-DRB1 alleles influence the development of RA. This study examined the influence of SE-negative HLA-DR alleles (DRB1*X) on the development of RA in 3 different French populations. METHODS: HLA-DRB1 alleles were defined by polymerase chain reaction with sequence-specific oligonucleotide hybridization or sequence-specific primers. SE-negative alleles were classified according to the electric charge of their P4 pocket. HLA-DRB1 alleles *0103, *0402, *07, *08, *11 (except *1107), *12, and *13 have a neutral or negative P4 charge and are called DRB1*XP4n. HLA-DRB1*03, *0403, *0406, *0407, *0901, *1107, *14, *15, and *16 have a positive P4 charge and are called DRB1*XP4p. RESULTS: Among the SE-negative subjects, DRB1 genotypes with 1 or 2 DRB1*XP4n alleles were significantly overrepresented in the control subjects compared with the RA patients, whereas DRB1*XP4p/XP4p genotypes were equally represented in the patients and controls. In single-dose SE-positive subjects, SE/XP4n genotypes were equally represented in the patients and controls. However, SE/XP4p genotypes were significantly overrepresented in the RA patients. CONCLUSION: The DRB1*X allele polymorphism influences susceptibility to RA. Alleles that have a neutral or negative electric charge in their P4 pocket (DRB1*XP4n), such as DRB1*0103, *0402, *07, *08, *11 (except *1107), *12, and *13, protect against RA. Alleles that have a positive electric charge in their P4 pocket (DRB1*XP4p), such as DRB1*03, *0403, *0406, *0407, *0901, *1107, *14, *15, and *16, have no influence on the predisposition to RA.

Alleles↗
PubMed2001

Fibromyalgia developed after administration of gonadotrophin-releasing hormone analogue.

We report the case of a woman treated with a gonadotrophin-releasing hormone analogue for endometriosis who developed typical clinical features of fibromyalgia, with widespread musculoskeletal pain, sleep difficulties, neuropsychological complaints and tender points on clininal examination. The gonadotrophin-releasing hormone analogue treatment probably induced disturbances in the neuroendocrine system and the secretion of neurotransmitters, and may be suspected to be the cause of this case of fibromyalgia.

Adult↗
PubMed2001

Adult hypophosphatasia. Current aspects.

Hypophosphatasia is an inborn metabolic disorder in which abnormally low levels of the enzyme nonspecific alkaline phosphatase result in defective skeletal and dental mineralization (rickets, fractures, dental abnormalities) and in accumulation of the enzyme substrates (phosphoethanolamine, pyridoxal-5'phosphate and inorganic pyrophosphate). The build-up of inorganic pyrophosphate promotes the development of articular chondrocalcinosis. There are several forms of hypophosphatasia, with wide variations in severity. We report the case of a 53-year-old man with typical manifestations of moderate adulthood hypophosphatasia. Investigations in his family found the disease in a sister and two children. He had two autosomal mutations, which were transmitted recessively. Several mutations of the alkaline phosphatase gene have been identified. The genotype is correlated with the phenotype: some mutations are associated with milder forms and others with more severe forms of the disease.

Age of Onset↗
PubMed2001

Bone density, ultrasound measurements and body composition in early ankylosing spondylitis.

OBJECTIVES: In this cross-sectional study, we evaluated bone density using both dual-energy X-ray absorptiometry (DEXA) and quantitative ultrasound (QUS) techniques and examined the changes in body composition in patients with ankylosing spondylitis (AS). METHODS: Seventy-one patients were compared with seventy-one sex- and age-matched controls. Bone mineral density (BMD) was evaluated at the lumbar spine and femoral neck with a Lunar device. Total body measurements were also performed, giving BMD and bone mineral content (BMC) of the whole body, and fat and lean masses. Broadband ultrasound attenuation (BUA), speed of sound and stiffness were measured at the calcaneus using an Achilles ultrasound device. RESULTS: The patients had significantly lower lumbar spine, femoral neck and total body BMD as compared with controls (all P < 0.05). Total body BMC was also decreased in AS (P = 0.002). On the contrary, fat and lean masses did not differ between patients and controls as observed for QUS values. Mild to good correlations were found between BMD and QUS parameters (r ranging from 0.22 to 0.53; all P < or = 0.01). When applying the World Health Organization (WHO) definition for osteoporosis, we found that 46.5% of patients had lumbar spine osteopenia and/or osteoporosis, while 26.8% had femoral neck osteopenia and/or osteoporosis (controls: 23.9 and 10%; P = 0.001 and 0.08, respectively). No relationships between disease activity (as evaluated by erythrocyte sedimentation rate, serum C-reactive protein levels and BASDAI, a clinical index of disease activity) and BMD measurements were found and only femoral neck BMD correlated with disease duration (r = -0.25; P = 0.04). Finally, the presence of talalgia in AS did not influence the QUS values. CONCLUSION: These results confirm that AS patients have decreased BMD values at both the spine and femur, and also in total body measurements, reflecting a generalized bone loss. On the contrary, soft tissue composition does not seem to be influenced by the disease. QUS parameters were found to be similar between patients and controls, suggesting that the QUS method did not provide additive information to DEXA. As it is thought that QUS provides information about qualitative properties of bone, the normal results of QUS values in our patient series argue against modifications in AS bone micro-architecture.

Absorptiometry, Photon↗
PubMed2001

Therapeutic advances in ankylosing spondylitis.

Ankylosing spondylitis (AS) is a systemic inflammatory rheumatic disease involving spinal and sacroiliac joints. This condition is responsible for back pain, stiffness, but also loss of functional capacity with socio-economic consequences. The management of AS includes patient education, rest, a programme of regular physical exercise, together with the use of NSAIDs. Second-line treatments are required in cases of severe or refractory AS, however only sulfasalazine has proven to benefit AS patients with peripheral arthritis. In spite of this management, the disease may not be adequately controlled, mainly for patients with refractory axial disease, enthesopathy or extra-articular features. Thus, new innovative treatments are needed for AS. It is likely that the new NSAIDs or COX-2 specific inhibitors will certainly take the place of the conventional NSAIDs, with regard to their superior tolerability. Methotrexate is a therapeutic option for AS treatment, but its usefulness in this disease remains to be established in adequate controlled studies. Finally, the TNF-alpha targeting drugs, namely thalidomide and the anti-TNF-alpha mAb, infliximab, have given promising results in the treatment of severe and/or refractory AS patients, however further controlled studies are required. In addition, the long-term use (efficacy and tolerability) of these two agents deserves attention.

Cyclooxygenase Inhibitors↗
PubMed2000

The association of HLA-DM genes with rheumatoid arthritis in Eastern France.

In this study, the polymorphisms of the HLA DMA and DMB genes in patients with rheumatoid arthritis (RA) were examined.DMA and DMB typing was performed in 120 white RA patients from eastern France and 100 healthy controls, using PCR-SSO (sequence specific oligonucleotide probes) method for DMA determination and PCR-RFLP (restriction fragment length polymorphism) method for DMB typing. All patients and controls had been HLA DRB1* genotyped.DMA*0103 was found significantly increased in RA patients (RA vs. controls: 18.3% vs. 4%) (p(corr) = 0.004; OR: 5.39; CI: 1.67-19.23). A decreased frequency of DMA*0102 was also observed in the RA group (RA vs. controls: 18.3% vs. 31%), but not significantly. There were no differences in the prevalence of DMB alleles between RA and controls. The patients and the controls were then stratified according to the expression of the HLA DRB1* RA-linked alleles (DRB1*01 and *04) and this allowed us to find no linkage disequilibrium between DMA*0103 and DRB1*01 or *04 alleles. Finally, most DMA*0103 patients were positive for rheumatoid factors and had extraarticular involvement such as subcutaneous nodules. Thus, our results suggest that DMA*0103 could be an additional genetic factor for RA susceptibility in French whites.

Adolescent↗
PubMed2000

[Infectious osteoarthritis due to Propionibacterium acnes. Two new cases].

INTRODUCTION: Propionibacterium acnes is an anaerobic germ, usually found as a saprophyte of the skin and the mucosa. It may be responsible for iatrogenic or spontaneous osteoarhritis. EXEGESIS: We report two new cases of septic arthritis induced by P. acnes: a case of iatrogenic spondylodiscitis and a case of spontaneous septic arthritis of the lumbar facet joints. The two patients were immunocompetent, without acne. CONCLUSION: Except for patients with criteria of the SAPHO syndrome (synovitis-acne-pustulosis-hyperostosis-osteomyelitis), osteoarthritis caused by P. acnes is increasingly described. The number of these infections is probably underestimated because of the technical problems involved in isolating P. acnes in the laboratory.

Acquired Hyperostosis Syndrome↗
PubMed2000

Decreased T cell precursor frequencies to Epstein-Barr virus glycoprotein Gp110 in peripheral blood correlate with disease activity and severity in patients with rheumatoid arthritis.

OBJECTIVES: Rheumatoid arthritis (RA) is a chronic joint disease associated with certain HLA-DR alleles expressing the QK/RRAA motif or shared epitope. The Epstein-Barr virus (EBV) has been suspected to be a causative factor for RA. The EBV gp110, a glycoprotein of the replicative cycle that contains a copy of the shared epitope, constitutes an important target in the immune control of EBV replication. This study evaluated the specific T cell response to EBV gp110 in patients with RA expressing or not the shared epitope and examined whether this immune cellular response might be related to disease activity and severity. METHODS: 25 patients with RA were studied and compared with 25 healthy controls. Disease activity was assessed by biochemical markers of inflammation (erythrocyte sedimentation rate (ESR) and C reactive protein (CRP) levels). Disease severity was defined by extra-articular disease (vasculitis, subcutaneous nodules, or other organ disease). The frequencies of peripheral blood T cells specific for EBV gp110 and a control protein (total protein extract from Escherichia coli) were determined by direct limiting dilution analysis without preliminary bulk culture. RESULTS: The gp110 precursor frequencies ranged from 0 to 20 x 10(-6) in patients with RA and controls. The mean gp110 T cell precursor frequency was lower in patients with RA (SD 3.2 (4.4) x 10(-6)) than in healthy controls (4.1 (3.8) x 10(-6)) (p = 0.02). No difference was found for the control protein (p = 0.09). Both shared epitope positive and negative patients with RA responded to gp110, without significant difference. A negative correlation between both ESR and CRP levels and the gp110 T cell response was found (r = -0.71, p<0.0001 and r = -0.42, p = 0.038, respectively). Finally, patients with extra-articular disease displayed the lowest immune cellular response to EBV gp110. CONCLUSION: These results suggest that patients with RA have a decreased T cell response to EBV gp110. Since gp110 is an important protein in the control of EBV replication, this might lead to a poor control of EBV infection, chronic exposure to other EBV antigens, and thus to a chronic inflammatory response in patients with RA.

Adult↗
PubMed2000

Thalidomide: a comeback?

Thalidomide, a synthetic glutamic acid derivative first marketed in 1954 as a sedative, rapidly gained worldwide notoriety as a cause of phocomelia. To prevent further cases of this severe birth defect, thalidomide was removed from the market. Over the last few years, however, thalidomide has been found to exhibit properties of potential usefulness in a range of conditions. Trials are under way in rheumatic diseases, and safer analogs have been developed.

Contraindications↗
PubMed2000

Amyloid arthropathy revealed by RS3PE syndrome.

Amyloid arthropathy is a form of primary AL amyloidosis with a monoclonal component in the blood and/or urine, and RS3PE syndrome is acute edematous polysynovitis in subjects older than 60 years. A 74-year-old man was diagnosed with both disorders. He was admitted for benign acute polyarthritis of the hands and feet and reported carpal tunnel symptoms predominating on the right. A synovial biopsy at the right wrist disclosed deposits that stained with Congo red even after potassium permanganate treatment (positive Wright's test). Articular AL amyloidosis was diagnosed. The symptoms resolved under glucocorticoid therapy alone, casting some doubt on their relationship with the amyloidosis. Roentgenograms showed geodes, a feature not present in RS3PE. Whether RS3PE may be among the possible presentations of articular amyloidosis is discussed.

Aged↗
PubMed1999

HLA-DR polymorphism influences T-cell precursor frequencies to Epstein-Barr virus (EBV) gp110: implications for the association of HLA-DR antigens with rheumatoid arthritis.

To study whether HLA-DR haplotypes associated with susceptibility to develop rheumatoid arthritis (RA) may influence T-cell responses to the Epstein-Barr virus (EBV) gp110 (a protein of the late replicative cycle of EBV), we evaluated the frequency in peripheral blood of T cells capable to proliferate to EBV gp110 by direct limiting dilution analysis in 50 HLA-DR-typed healthy subjects. NVe found that HLA-DRB1*07, an allele associated with reduced risk to develop RA, is associated with the highest frequencies of T cells specific for gp110 in peripheral blood. In contrast, HLA-DRB1*0404, one of the susceptibility alleles is associated with the lowest frequencies of gp110 specific T cells. Finally, people expressing both HLA-DRB1*07 and HLA-DRB1*0404 display low precursor frequencies to EBV gp110.

Animals↗
PubMed1999

Relationship between urinary pyridinium cross-links, disease activity and disease subsets of ankylosing spondylitis.

OBJECTIVE: In this study, we aimed to determine the urinary levels of pyridinium cross-links and urinary beta-isomerized fragments derived from the C-telopeptide of the alpha1 chain of type I collagen (beta-CTX) as markers of bone resorption in patients with ankylosing spondylitis (AS), and to study their relationship to markers of disease activity [erythrocyte sedimentation rate (ESR)] and to disease subsets of this condition. METHODS: The serum calcium, osteocalcin (OC), parathormone (PTH), 25 OHD3 levels, beta-CTX and the urinary combined free pyridinolines (f-Pyr + f-Dpyr), urinary free deoxypyridinoline (f-Dpyr) and urinary free pyridinoline (f-Pyr) were evaluated and compared in 32 AS patients and 25 controls. Bone mineral density (BMD) was evaluated at the lumbar spine and the femoral neck. RESULTS: The serum markers of bone metabolism (serum calcium, PTH, 25 OHD3 and OC) were in the normal range in the AS group. AS patients had a lowered lumbar spine BMD (P = 0.01) (corresponding T score: P = 0.03), but femoral neck BMD did not differ significantly between AS and controls (P = 0.08) (corresponding T score: P = 0.11). There was no difference in the urinary levels of pyridinium cross-links and beta-CTX between AS patients and controls. A positive correlation between ESR, (f-Pyr + f-Dpyr) (r = 0.42; P = 0.018) and f-Dpyr (r = 0.49; P = 0.005) was observed. In the different disease subsets of AS, we found that patients with peripheral involvement had higher (f-Pyr + f-Dpyr) (P = 0.04) and f-Dpyr levels (P = 0.04), patients with early disease had elevated (f-Pyr + f-Dpyr) (P = 0.01), f-Dpyr (P = 0.02) and f-Pyr (P = 0.01) levels, and that those with raised ESR had enhanced f-Dpyr (P = 0.009) excretion. Patients were then stratified according to disease duration, peripheral involvement and sex, and this allowed us to observe that only urinary f-Dpyr remained elevated in patients independently from these variables and that raised ESR is the more relevant parameter for explaining this high level of excretion. CONCLUSION: We conclude that there was no difference in the levels of urinary pyridinium cross-links and beta-CTX between AS and controls. However, urinary excretion of some of these collagen compounds was enhanced in subgroups of AS, mainly in patients with raised ESR. Thus, AS patients with laboratory evidence of active disease could have a higher risk of bone loss.

Absorptiometry, Photon↗
PubMed1999

Rheumatic disorders developed after hepatitis B vaccination.

OBJECTIVE: To obtain an overview of rheumatic disorders occurring after hepatitis B vaccination. METHODS: A questionnaire was sent to rheumatology departments in nine French hospitals. Criteria for entry were rheumatic complaints of 1 week's duration or more, occurrence during the 2 months following hepatitis B vaccination, no previously diagnosed rheumatic disease and no other explanation for the complaints. RESULTS: Twenty-two patients were included. The observed disorders were as follows: rheumatoid arthritis for six patients; exacerbation of a previously non-diagnosed systemic lupus erythematosus for two; post-vaccinal arthritis for five; polyarthralgia-myalgia for four; suspected or biopsy-proved vasculitis for three; miscellaneous for two. CONCLUSIONS: Hepatitis B vaccine might be followed by various rheumatic conditions and might trigger the onset of underlying inflammatory or autoimmune rheumatic diseases. However, a causal relationship between hepatitis B vaccination and the observed rheumatic manifestations cannot be easily established. Further epidemiological studies are needed to establish whether hepatitis B vaccination is associated or not with an incidence of rheumatic disorders higher than normal.

Adolescent↗