Search PubMed⌕ Search

Biomedical subjects

P Miossec

Publications and source records attributed to P Miossec.

At least 19 recordsLinked to original sources
PubMed2006

Extensive multiallelic analysis of the relationship between HLA-DRB1 and rheumatoid arthritis using a Bayesian partition model.

To analyse the association between individual HLA-DRB1 locus genotypes and rheumatoid arthritis (RA) susceptibility, taking in account the multiallelic nature of the shared epitope (SE). In total, 538 patients and 536 controls were genotyped for 12 alleles of the HLA-DRB1 locus. A Bayesian partition model and multivariate logistic models were used to assess the role of the SE and of its individual components. The SE was associated with RA susceptibility (odds ratio (OR) 2 versus 0 SE copy=9.99 (95 CI 4.69-15.30) and OR 1 versus 0 SE copy=3.16 (95% CI 2.42-4.12)). The Bayesian partition model supplied a permutation of the HLA-DRBA locus alleles ordered by increasing disease risk. Alleles associated with highest risks are those that code for the SE. The individual OR estimations for the HLA-DRB1 locus genotypes went from OR=1.00 (95% CI 1.00-1.25) for the less associated genotype to OR=21.40 (95% CI 8.02-65.79) for the most associated one. In conclusion, the allele order risk and the OR estimations for individual genotypes of the HLA-DRB1 locus were consistent with the SE theory. Using an exploratory statistical method without a priori hypothesis, our study allowed a detailed analysis of the multiallelic nature of the SE.

Adult↗
PubMed2006

Etanercept treatment for three months is safe in patients with rheumatological manifestations associated with hepatitis C virus.

OBJECTIVE: The treatment of the rheumatological manifestations associated with hepatitis C virus (HCV) remains difficult. To examine the safety of anti-tumour necrosis factor-alpha treatment, nine patients having rheumatological manifestations associated with HCV were treated with etanercept 25 mg twice a week for 3 months. METHODS: Five patients had a positive viral load at study entry (Group I), four were negative (Group II). Clinical data recorded were: disease duration, painful and swollen joint count, patient global and physician global assessment, the number of 18 specified fibromyalgia tender points and the Health Assessment Questionnaire score. Laboratory studies included checking for the presence of cryoglobulinaemia and transaminase levels. Quantitative HCV viral RNA was performed by real-time polymerase chain reaction (PCR). RESULTS: At 3 months, no patient was found to have evidence of increased hepatic inflammation based on serial serum transaminase levels. In the five patients from Group I with detectable HCV RNA, no significant viral load increase was observed. No reactivation was observed in the four patients from Group II with undetectable HCV RNA. The effect on the clinical rheumatological manifestations was more heterogeneous but appears to be lower than that observed in rheumatoid arthritis. CONCLUSION: In this phase II open short-term study, etanercept appeared to be safe in patients with articular manifestations associated with HCV.

Antirheumatic Agents↗
PubMed2006

Novel aspects on the contribution of T cells and dendritic cells in the pathogenesis of myositis.

This review focuses on recent advances and new hypothesis in the understanding of the T and dendritic cells contribution to the pathogenesis of idiopathic inflammatory myopathies (IIMs), especially polymyositis (PM) and dermatomyositis (DM). The new data show that non-specific amplification of muscle inflammation by T lymphocyte and dendritic cells may result from the local production of cytokines and chemokines. Synergistic interactions between these factors explain some of the clinical features. The potent role of these molecules suggests their potential for therapeutic manipulation using specific inhibitors.

Animals↗
PubMed2005

The association between periodontal disease and joint destruction in rheumatoid arthritis extends the link between the HLA-DR shared epitope and severity of bone destruction.

OBJECTIVE: To evaluate a possible association between wrist and periodontal destruction in rheumatoid arthritis, and between periodontal destruction, dry mouth, and labial salivary gland biopsy and the contribution of genetic factors (the shared epitope (SE) and IL1B (+3954) or TNFA (-238 or -308) gene polymorphisms). METHODS: 147 patients with rheumatoid arthritis were enrolled. Periodontal damage was defined according to the Hugoson and Jordan criteria on panoramic dental x rays. Typing for the SE and cytokine polymorphisms was undertaken by enzyme linked oligosorbent assay. Odds ratios (OR), relative risk (RR), and chi2 values were calculated to quantify associations. RESULTS: An association was observed between wrist and periodontal bone destruction (chi2=11.82; p<0.001): 63 patients had both wrist and periodontal destruction, 31 had wrist destruction alone, 20 had periodontal destruction alone, and 33 had no destruction at either site. An association was seen between a positive labial salivary gland biopsy and periodontal bone destruction (RR=2.73 (95% CI, 1.35 to 5.51), p<0.01, n=41) or wrist bone destruction (RR=4.52 (1.96 to 10.45), p<0.001, n=41). The SE was associated with wrist bone destruction (OR=2.5 (1.16 to 5.42), p<0.05) and periodontal bone destruction (OR=2.2 (1.04 to 4.84), p<0.05). No association was found between the selected cytokine polymorphisms and bone destruction. CONCLUSIONS: A strong association was found between wrist and periodontal bone destruction. The destruction risk was further increased in patients with sicca syndrome. The SE appears to be a severity genetic marker for both wrist and periodontal bone destruction.

Aged↗
PubMed2005

The shared epitope is a marker of severity associated with selection for, but not with response to, infliximab in a large rheumatoid arthritis population.

OBJECTIVE: To determine whether joint destruction, indication for, and response to infliximab in rheumatoid arthritis are associated with the shared epitope (SE) or selected cytokine gene polymorphisms (interleukin (IL) 1B, IL1-RN, and tumour necrosis alpha). METHODS: In a large rheumatoid arthritis population of 930 patients from the same area (Rhône-Alpes, France), patients with (n = 198) or without infliximab treatment (n = 732) were compared according to their genetic status. Clinical, biological, and radiological data were collected. Typing for SE status and cytokine polymorphisms was carried out using enzyme linked oligosorbent assay. Statistical analysis was by chi(2) testing and calculation of odds ratios (OR). RESULTS: A dose relation was observed between the number of SE copies and joint damage in the whole rheumatoid population (OR, 1 v 0 SE copy = 2.38 (95% confidence interval, 1.77 to 3.19), p<0.001; OR 2 v 0 SE copy = 3.92 (2.65 to 5.80), p<0.001. The SE effect increased with disease duration but was not significant before two years. Selection for infliximab treatment (n = 198) was associated with increased disease activity, joint damage, and the presence of the SE with a dose effect. In all, 66.2% patients achieved an ACR20 improvement. No clinical or genetic factors were able to predict the clinical response to infliximab. CONCLUSIONS: This post-marketing study in a large cohort of rheumatoid arthritis patients indicates a linkage between rheumatoid arthritis severity, selection for treatment with infliximab, and the presence and dose of the SE.

Adult↗
PubMed2005

Rheumatological manifestations of hepatitis C: incidence in a rheumatology and non-rheumatology setting and the effect of methotrexate and interferon.

OBJECTIVES: To evaluate hepatitis C virus (HCV)-positive patients followed in a rheumatology department and to compare them with a similar population of HCV-positive patients who had never seen a rheumatologist, in order to describe the rheumatological symptoms present and the effects of methotrexate and interferon-alpha therapy. METHODS: We performed a retrospective study of clinical, radiological and biological data on 21 rheumatology patients (Group I) presenting symptoms consistent with a chronic inflammatory arthritis with a known HCV infection and compared them with 41 members of an HCV support association (Group II). RESULTS: Symptoms of myalgia, sicca syndrome, Raynaud's phenomenon or paraesthesias were similarly frequent in the two groups. However, inflammatory joint pain and joint swelling were more common in Group I. In this group rheumatoid factor was positive in 48%, antinuclear antibodies in 26%, cryoglobulin in 44% and a reduced complement level in 63%. The majority of patients from Group I treated with methotrexate demonstrated an amelioration of the rheumatological symptoms with few negative outcomes. Regarding interferon-alpha therapy and rheumatological symptoms-in Groups I and II respectively 50 and 66% demonstrated a deterioration, 33 and 30% showed no change and 17 and 4% showed an amelioration. CONCLUSION: Rheumatological symptoms are common in patients chronically infected with HCV. It is essential to individualize the role of treatment with interferon-alpha and to consider the use of methotrexate for difficult cases.

Adult↗
PubMed2005

Contribution of tumour necrosis factor alpha and interleukin (IL) 1beta to IL6 production, NF-kappaB nuclear translocation, and class I MHC expression in muscle cells: in vitro regulation with specific cytokine inhibitors.

OBJECTIVE: To evaluate the effect of tumour necrosis factor alpha (TNFalpha), interleukin (IL) 1beta, and their respective inhibitors the p75 TNFalpha soluble receptor (sTNFR) and the type II sIL1betaR (sIL1RII) on whole muscle and isolated myoblast activation. METHODS: Normal muscle samples were stimulated for 7 days with TNFalpha alone or in combination with IL1beta, and myoblasts from these samples for 48 hours. IL6 production was measured by ELISA. Nuclear translocation of NF-kappaB was analysed by immunofluorescent staining and class I MHC expression by FACS. RESULTS: TNFalpha and IL1beta induced IL6 production by normal muscle samples and myoblasts, the action of TNFalpha being more potent on muscle samples. Their soluble receptors (1 microg/ml) decreased this production. Suboptimal concentrations of TNFalpha and IL1beta induced NF-kappaB translocation. sTNFR markedly down regulated TNFalpha-induced translocation while sIL1RII was less potent on IL1beta-induced activation. NF-kappaB translocation induced by the combination of optimal concentrations of TNFalpha and IL1beta was completely inhibited by their soluble receptors. TNFalpha and to a lesser extent IL1beta induced class I MHC expression by myoblasts and this effect was completely inhibited by their respective soluble receptors. CONCLUSION: These results suggest that TNFalpha and IL1beta should be targeted for myositis treatment.

Dose-Response Relationship, Drug↗
PubMed2005

Lupus erythematosus with leflunomide: induction or reactivation?

BACKGROUND: Leflunomide is a new oral disease modifying antirheumatic drug with a good safety profile. CASE REPORT: The first case of lupus erythematosus in a 58 year old white woman after administration of leflunomide for primary Sjögren's syndrome is reported. The relationship between induced lupus and leflunomide was confirmed by the resolution of the skin rash when the drug was stopped and its recurrence when it was reintroduced following a dose-response effect. DISCUSSION: Peripheral blood cells from this patient, from 15 patients with rheumatoid arthritis, and from healthy controls were used in a bioassay, which suggested that leflunomide affected the Th1/Th2 balance. Such a side effect might be related, in part, to the anti-tumour necrosis factor alpha activity of leflunomide.

Antirheumatic Agents↗
PubMed2004

Effect of treatment of rheumatoid arthritis with infliximab on IFN gamma, IL4, T-bet, and GATA-3 expression: link with improvement of systemic inflammation and disease activity.

OBJECTIVE: To study interferon gamma (IFN gamma) production and the expression of T-bet and GATA-3, the transcription factors associated with Th1 and Th2, in peripheral blood mononuclear cells (PBMC) from patients with rheumatoid arthritis before and during infliximab treatment, so as to distinguish between a disease specific and a disease activity dependent defect. METHODS: Rheumatoid PBMC were obtained at weeks 0 and 6 of infliximab treatment and cultured for seven days with or without interleukin (IL)12 or the combination of IL12 and IL18. IFN gamma concentrations in supernatants were determined by ELISA. mRNA expression of IFN gamma, IL4, T-bet, and GATA-3 was determined by real time RT-PCR in whole blood at weeks 0 and 22. RESULTS: A reduction in spontaneous IFN gamma production and in the response to Th1 inducing cytokines occurred in rheumatoid PBMC. Reduction of systemic inflammation with infliximab treatment increased IFN gamma production in response to IL12 or IL12+IL18. The IFN gamma/IL4 expression ratio of rheumatoid blood before treatment was lower than in healthy controls but was increased by infliximab treatment. T-bet expression or T-bet/GATA-3 ratio of rheumatoid blood was less than in controls. The T-bet/GATA-3 ratio was not influenced by infliximab treatment. CONCLUSIONS: Regulation of T-bet and GATA-3 or IFN gamma and IL4 expression appeared different. The IFN gamma/IL4 ratio might express the blood Th1/Th2 balance better than the T-bet/GATA-3 ratio. Reduced IFN gamma production by rheumatoid PBMC and levels of IFN gamma and IL4 mRNA expression in blood were linked to disease improvement, indicating an association between this systemic Th1 feature and disease activity.

Adult↗
PubMed2004

Serum levels of type IIA procollagen amino terminal propeptide (PIIANP) are decreased in patients with knee osteoarthritis and rheumatoid arthritis.

OBJECTIVE: The aim of this study was to develop a specific immunoassay for PIIANP and measure its serum concentration in healthy controls and in patients with osteoarthritis (OA) and rheumatoid arthritis (RA). In addition, we investigated circulating forms recognized by antiserum IIA in pools of serum from healthy adults, patients with OA and patients with RA. DESIGN: Using as immunogen and standard the recombinant human Glutathione S-Transferase (GST)-exon 2 fusion protein of type II collagen, we developed a competitive polyclonal antibody-based ELISA. We compare serum PIIANP levels in 43 patients with knee OA (23 women and 20 men; mean age: 62.6+/-9.6 yr), 63 women with RA (mean age: 54+/-16 yr) and 88 healthy controls (67 women, mean age: 53+/-13 yr and 21 men, mean age: 63+/-7 yr). We randomly selected serum in each group for analyze circulating forms. RESULTS: The immunoassay we developed demonstrated adequate intra and inter-assay precision (CV<10%) and dilution recovery (mean: 96%), allowing accurate measurements of serum PIIANP from 1.13 to 40 ng/ml. No significant cross-reactivity of the ELISA was observed with purified intact human procollagen type I N-propeptide, circulating thrombospondin and von Willebrand factor, proteins which exhibit significant sequence homology with PIIANP. Western blot analysis showed that antiserum IIA recognized two circulating immunoreactive forms of approximately 80 and 100 KDa respectively in serum from healthy adults, patients with OA and RA but also in a pool of synovial fluids from patients with OA. Serum PIIANP levels were markedly decreased in patients with knee OA (12.0+/-3.2 vs 25.8+/-7.5 ng/ml for OA and controls respectively, P<0.0001) and RA (14.1+/-2.5 ng/ml vs 21.7+/-7.6 ng/ml for RA and controls respectively, P<0.0001). In patients with RA, serum PIIANP levels were higher in those taking low-dose prednisone compared to non-users (15.0+/-2.4 vs 13.5+/-2.4 ng/ml, P<0.05). CONCLUSIONS: We have developed the first specific immunoassay for serum PIIANP which exhibits adequate technical performances. This assay detects specifically two immunoreactive forms both in healthy adults and patients with arthritis and does not cross react with other proteins with sequence homology with PIIANP. Levels of PIIANP were significantly decreased in patients with knee OA and RA suggesting that type IIA collagen synthesis may be altered in these arthritic diseases. The measurement of type IIA collagen synthesis with this new molecular marker may be useful for the clinical investigation of patients with joint diseases.

Adult↗
PubMed2004

Better efficacy of methotrexate given by intramuscular injection than orally in patients with rheumatoid arthritis.

OBJECTIVE: To compare the clinical efficacy of methotrexate and tolerance to the drug in patients with rheumatoid arthritis who were switched from intramuscular to oral administration because of a shortage of the intramuscular preparation. METHODS: 143 patients were switched from intramuscular to oral methotrexate. Of these, 47 were switched back to the intramuscular form. A multiple choice questionnaire was sent by mail to evaluate clinical and biological criteria of efficacy and tolerance. RESULTS: When methotrexate was first switched from intramuscular to oral administration, increased disease activity, exacerbation of morning pain and hand stiffness, duration of morning stiffness, increased joint pain, and increased joint swelling were observed. There was a greater frequency of gastrointestinal symptoms, but without a significant increase in liver abnormalities. When intramuscular methotrexate became available again, 47 of the 143 patients were switched back and were followed for at least three months. On average, disease manifestations were improved and side effects reduced by the switch. CONCLUSIONS: Methotrexate given intramuscularly had improved clinical efficacy with fewer side effects than given orally. Intramuscular methotrexate administration should be considered when rheumatoid arthritis remains active in spite of high dose oral methotrexate.

Administration, Oral↗
PubMed2003

Interleukin-17 increases the effects of IL-1 beta on muscle cells: arguments for the role of T cells in the pathogenesis of myositis.

We studied the production of interleukin (IL)-6 and CCL20/macrophage inflammatory protein-3 alpha (MIP-3 alpha) by human myoblasts and muscle samples in response to IL-17 alone or in combination with IL-1 beta. Both IL-17 and IL-1 beta induced IL-6 production by normal myoblasts and muscle samples. IL-17 had no effect on CCL20 production by myoblasts. Combination of IL-17 and IL-1 beta further increased IL-6 and CCL20 production by muscle samples but not that of CK. IL-17 induced also HLA class I, C-Fos, nuclear factor kappa B (NF-kappa B) and C-Jun expression by myoblasts but not that of HLA class II, CD40, vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1). Finally, immunostaining of dermatomyositis (DM) and polymyositis (PM) muscle biopsies showed IL-17 and CCL20 expression. Our study shows that low levels of cytokines produced by T cells (IL-17) and monocytes (IL-1 beta) can act in combination on skeletal myoblasts and muscle tissue.

Adjuvants, Immunologic↗
PubMed2003

Lack of evidence for a direct involvement of muscle infection by parvovirus B19 in the pathogenesis of inflammatory myopathies: a follow-up study.

OBJECTIVE: To clarify the association between parvovirus B19 and myositis. METHODS: Biopsy samples of muscle from eight patients with inflammatory myopathies were studied for the presence of B19 DNA by polymerase chain reaction. Expression of VP1 and VP2 capsid proteins was evaluated by immunohistochemistry. Interleukin 6 (IL-6) production was measured in the supernatant of myoblasts following incubation with parvovirus B19. RESULTS: In seven samples, detection of B19 DNA was negative. The expression of VP1 and VP2 capsid proteins was not observed by immunohistochemistry. In one patient, detection was transiently positive but became negative despite a flare-up of muscle disease. In vitro, parvovirus B19 was not able to induce IL-6 production by myoblasts. CONCLUSION: Our results do not support the direct implication of parvovirus B19 in the pathogenesis of myositis.

Adolescent↗
PubMed2002

Addition of interleukin 1 (IL1) and IL17 soluble receptors to a tumour necrosis factor alpha soluble receptor more effectively reduces the production of IL6 and macrophage inhibitory protein-3alpha and increases that of collagen in an in vitro model of rheumatoid synoviocyte activation.

OBJECTIVES: To evaluate the usefulness of combination treatment with cytokine inhibitors. METHODS: A simplified model was set up to evaluate the effect of tumour necrosis factor alpha (TNFalpha) soluble receptors (sTNFR) used alone and in combination with soluble interleukin 1 receptor (sIL1R) and sIL17R on the production of markers of inflammation (IL6), of migration of dendritic cells (macrophage inhibitory protein-3alpha (MIP-3alpha)), and of matrix synthesis (C-propeptide of type 1 collagen (P1CP)). Synoviocytes were stimulated with supernatants of activated peripheral blood mononuclear cells (PBMC) from patients with rheumatoid arthritis (RA). Soluble receptors (sR) were preincubated at 1 gammag/ml alone or in combination with the supernatants before addition to RA synoviocytes. IL6, MIP-3alpha, and P1CP production was measured by enzyme linked immunosorbent assay (ELISA) in 48 hour synoviocyte supernatants. RESULTS: IL6 production decreased by 16% with sTNFR alone compared with no sTNFR (p<0.001) and by 41% with the combination of the three sR (p<0.001). MIP-3alpha production decreased by 77% with sTNFR alone compared with no sTNFR (p<0.001) and by 98% with the combination of the three sR (p<0.001). In the presence of sTNFR alone, P1CP production increased by 25% compared with no sR (p<0.01). The combination of the three sR increased P1CP production by 48% (p<0.01). CONCLUSION: The effect of sTNFR on IL6, MIP-3alpha, and P1CP production by RA synoviocytes stimulated by activated PBMC supernatants was further enhanced when combined with sIL1R and sIL17R.

Adult↗
PubMed2001

Infliximab-induced aseptic meningitis.

We report an episode of aseptic meningitis in a 53-year-old man, who was treated with infliximab for active rheumatoid arthritis. He had acute, severe muscle pain after initial infusion of the drug, and similar symptoms with a transient lymphocytic meningitis after a subsequent infusion. We measured no change in antibodies to nuclei, DNA, or to neurones. Functional antibodies to infliximab were not induced and concentrations of tumour necrosis factor a in spinal fluid were not raised. This adverse reaction to infliximab might have been caused by inability of the drug to enter the central nervous system.

Antibodies, Monoclonal↗