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Biomedical subjects

Olivier Meyer

Publications and source records attributed to Olivier Meyer.

At least 19 recordsLinked to original sources

Clinical practice format for choosing a second-line disease modifying anti-rheumatic drug in early rheumatoid arthritis after failure of 6 months' first-line DMARD therapy.

BACKGROUND: The objective was to develop a clinical practice format for choosing a second-line disease-modifying anti-rheumatic drug (DMARD) after a 6-month course of a first-line DMARD in patients with early RA. METHODS: A panel of 34 experts selected treatment option from various scenarios using the Thurstone pairwise method. The experts had to choose between two proposed DMARDs without proposing other options. The scenarios were obtained using the three items: DAS28, rheumatoid factor status and radiographic structural damage. A sample of 240 among 480 scenarios for each expert was taken at random. Responses given by at least 20% of the experts were considered pertinent. RESULTS: Recommendations for choosing a second DMARD for early RA after failure of a 6-month course of a first-line DMARD were established according to 4 parameters: type of first-line DMARD, activity, RF status and radiographic joint damage. The results of this study suggest that in patients with early RA who fail a 6-month course of first-line DMARD therapy, the best options may be addition of corticosteroid when disease activity is moderate to high and switching to a biologic agent when further radiographic joint damage occurs, particularly in patients with positive tests for RF. CONCLUSION: Although our scenarios did not include step-up (add instead of substitute) strategies, except for corticosteroids, we feel that the format presented here can optimise the management of patients with early RA seen in clinical practice.

Antirheumatic Agents↗

Neuropsychiatric manifestations of systemic lupus erythematosus.

Central nervous system (CNS) involvement in systemic lupus erythematosus (SLE) can produce a broad range of disease-specific neuropsychiatric manifestations that must be differentiated from infections, metabolic complications, and drug-induced toxicity. Despite the development of classification criteria by the American College of Rheumatology, the prevalence of neuropsychiatric systemic lupus erythematosus (NPSLE) varies widely across studies. Some of the neuropsychiatric manifestations are extremely rare, indicating a need for multicenter studies. Mechanisms that can lead to neuropsychiatric manifestations include intracranial vascular lesions (vasculitis and thrombosis); production of autoantibodies to neuronal antigens, ribosomes, and phospholipids; and inflammation related to local cytokine production. As a rule, no reference standard is available for establishing the diagnosis of NPSLE. Several investigations can be used to assist in the clinical diagnosis and to evaluate severity. Treatment remains largely empirical, given the absence of controlled studies. Variable combinations of corticosteroids, immunosuppressants, and symptomatic drugs are used according to the presumptive main pathogenic mechanism.

Humans↗

Health assessment questionnaire score is the best predictor of 5-year quality of life in early rheumatoid arthritis.

OBJECTIVE: To evaluate and determine prognostic factors of 5-year quality of life in patients with early rheumatoid arthritis (RA). METHODS: A cohort of 191 patients with RA and disease duration < 1 year was prospectively followed over 5 years. The outcome measure was quality of life as assessed by the Arthritis Impact Measurement Scales 2 (AIMS2). Univariate analysis, then stepwise multiple logistic regression, was used to find independent baseline prognostic variables. RESULTS: After accounting for death, loss of followup, and missing data, 158 patients (82.72%) were included in the analysis. The mean AIMS2 physical, symptom, psychological, social interaction, and work scores after 5 years were 1.6 (range 0-6.88), 4.0 (0-10), 3.48 (0-9.22), 4.06 (0-8.69), and 1.87 (0-8.13), respectively. The AIMS2 physical component was significantly correlated with Health Assessment Questionnaire (HAQ) score at 5 years. Logistic regression analysis revealed that the baseline values able to predict the 5-year physical, psychological, symptom, social interaction, and work status were, respectively: HAQ score and erythrocyte sedimentation rate (ESR), body mass index (BMI), HAQ; erosion score and sex, HAQ; ESR and anti-perinuclear antibody; matrix metalloproteinase-3 (MMP3) level, joint space narrowing, and tender joint scores; HAQ score and age. CONCLUSION: The multidimensional structure of the AIMS2 allowed us to assess the 5-year health-related quality of life in early RA. Using this instrument as an outcome variable, prognostic factors were selected and varied widely depending on the evaluated domain. The baseline HAQ score was the best predictive factor of 4 of the 5 domains of the AIMS2.

Adult↗

Predominant cervical involvement in patients with psoriatic arthritis: report of two cases.

Cervical spine involvement is common but usually delayed in patients with psoriatic arthritis. We report two cases with early and predominant involvement of the upper cervical spine. Synovitis of the atlanto-odontoid joint and fusion of multiple facet joints were noted in one patient. In the other patient, the main finding was atlanto-axial subluxation with erosions of the odontoid process and anterior arch of C1. No abnormalities were noted in the peripheral joints, sacroiliac joints, or thoracolumbar spine. Analgesics and conventional antiinflammatory agents were only minimally effective. TNFalpha antagonist therapy (infliximab followed by etanercept) in one patient and phenylbutazone therapy in the other improved the symptoms and led to shrinkage of the pannus.

Adult↗

Prognostic markers for systemic sclerosis.

The prognosis of systemic sclerosis depends chiefly on the extent of the skin lesions, which correlates with the severity of the cardiovascular, pulmonary, and renal manifestations. An erythrocyte sedimentation rate greater than 15-25 mm/h or a hemoglobin level lower than 12.5-11 g/dl is associated with a 2.5- to 3-fold increase in mortality. Anticentromere antibodies are associated with delayed pulmonary hypertension, anti-topoisomerase I antibodies (Scl 70) with interstitial lung disease, and anti-RNA polymerase III antibodies with renovascular hypertension. The risk of death is directly related to the autoantibody pattern. For instance, in a study of 1432 cases from the Pittsburgh Scleroderma Databank, 10-year survival among patients with limited cutaneous disease was 88% in the group with anti-U1-RNP, 75% in the group with anticentromere antibodies, 72% in the group with anti-PmScl, and 65% in the group with anti-Th/To. Ten-year survival in patients with diffuse cutaneous disease was 64% with anti-topoisomerase antibodies, 61% with anti-U3-RNP, and 75% with anti-RNA polymerase III. Several prognostic markers are also available for predicting the risk of organ involvement. For instance, serum levels of KL-6, surfactant proteins SP-A and SP-D, the collagen peptide PIIINP, and homocysteine are associated with the risk of fibrosing alveolitis. Serum levels of CD40L and NP-ProBNP, circulating endothelial cells, and serum anticardiolipin titers correlate with the risk of arterial hypertension. Serum VCAM1 and markers for oxidative stress such as carboxyl terminus residues predict the risk of vascular disease. Other serum markers for organ involvement are under study, although their predictive performance remains to be evaluated.

Autoantibodies↗

Anti-endothelial cell antibodies from patients with limited cutaneous systemic sclerosis bind to centromeric protein B (CENP-B).

By using a quantitative immunoblotting technique on protein extracts of human macrovascular and microvascular endothelial cells, we have analyzed the self-reactive repertoires of IgG from 20 patients with limited cutaneous SSc, 40 patients with diffuse SSc and 60 age- and sex-matched healthy controls. Serum IgG from 15/20 patients with limited cutaneous SSc and anti-centromere antibodies bound to at least one of the two 75- and 85-kDa protein bands in the different endothelial cell extracts, whereas IgG from healthy controls or patients with diffuse SSc did not. N-terminal sequencing of the 75- and 85-kDa bands identified CENP-B as the sole antigen in both bands. Moreover, IgG from all of the SSc patients who recognized the 75- and/or 85-kDa bands bound to a full-length recombinant CENP-B protein as assessed by ELISA, whereas IgG from other SSc patients did not. The main target of anti-endothelial cell antibodies in patients with limited cutaneous SSc is the nuclear and ubiquitous protein CENP-B.

Antibody Specificity↗

Serial determination of cyclic citrullinated peptide autoantibodies predicted five-year radiological outcomes in a prospective cohort of patients with early rheumatoid arthritis.

The objective of this study was to evaluate the potential of serially determined anti-cyclic citrullinated peptide (CCP) antibodies for predicting structural joint damage in patients with early rheumatoid arthritis (RA), compared to a single baseline determination. Ninety-nine RA patients with disease durations of less than one year and no history of disease-modifying antirheumatic drug therapy were followed prospectively for at least five years. Anti-CCP2 concentrations were measured using a second-generation ELISA. Sharp scores as modified by van der Heijde were determined on hand and foot radiographs. Anti-CCP2 antibodies were detected in 55.5% of patients at baseline and 63.6% at any time during the first three years. Presence of anti-CCP2 at any time during the first three years was associated with radiographic damage at baseline (odds ratio (OR), 3.66; 95% confidence interval (95% CI) 0.99-13.54) and with five year progression of the total Sharp score (OR, 3.17; 95% CI, 1.3-7.7), erosion score (OR, 5.3; 95% CI, 1.4-19.2) and joint space narrowing score (OR, 2.8; 95% CI, 1.15-6.8). The presence of anti-CCP2 or IgM RF at baseline did not predict these outcomes. Patients with negative anti-CCP2 tests throughout follow-up had less radiographic progression than patients with increasing anti-CCP2 concentrations; they did not differ from patients with decreasing anti-CCP2 antibody levels. HLADRB1* typing showed that progression of the mean modified Sharp score was not correlated with the presence of the shared epitope alleles. In conclusion, serially determined anti-CCP2 antibodies during the first three years of follow-up performs better than baseline determination for predicting radiographic progression in patients with early RA.

Arthritis, Rheumatoid↗

52-kDa Ro/SSA epitopes preferentially recognized by antibodies from mothers of children with neonatal lupus and congenital heart block.

Neonatal lupus erythematosus is a rare disorder caused by the transplacental passage of maternal autoantibodies. The 52-kDa Ro/SSA antigen (Ro52) ribonucleoprotein represents an antigenic target strongly associated with the autoimmune response in mothers whose children have neonatal lupus and cardiac conduction disturbances, mainly congenital heart block. The objective of this study was to identify putative Ro52/60-kDa Ro/SSA antigen (Ro60) epitopes associated with neonatal lupus and congenital heart block. The reactivity of IgG antibodies present in the sera from mothers with systemic lupus erythematosus and Sjögren's syndrome and in the sera from asymptomatic mothers (a longitudinal study of 192 samples from 66 subjects) was investigated by ELISA using Ro52, Ro60 and 48-kDa La/SSB antigen proteins, as well as 45 synthetic peptides, 13-24 residues long, of Ro52/Ro60 proteins. One to 19 samples collected before, during and after pregnancy were available for each mother. Forty-three disease controls selected randomly and normal sera were tested in parallel. Although no differences were found between Sjögren's syndrome and asymptomatic mothers of group I, who had at least one infant with neonatal lupus, and of group II, who had healthy babies only, significant differences were observed between lupus mothers from both groups. In the former group of lupus mothers, a significantly higher frequency of antibodies to Ro52 peptides 107-122 and 277-292 was observed. Between 18 and 30 weeks of gestation, the period of risk, there was clearly an elevated level of antibodies reacting with Ro52 peptides 1-13, 277-292 and 365-382. Antibodies to Ro52 peptide 365-382 have been shown previously to cross-react with residues 165-185 of the heart 5-HT4 serotoninergic receptor, and might be pathologically important. The level of these Ro52 antibody subsets decreased at the end of pregnancy and after delivery. IgG antibodies to Ro52 peptides 1-13, 107-122, 277-292 and 365-382 may therefore represent important biomarkers to predict a complication in pregnant lupus women with Ro52 antibodies.

Adult↗

Rheumatoid nodulosis. Two cases with destructive polyarthritis after 20 years.

The term "rheumatoid nodulosis" was coined by Ginsberg in 1975 to designate a rare and distinctive form of rheumatoid disease. Anecdotal case reports suggest a benign nondestructive course, although prolonged follow-up data are usually unavailable. We describe two cases of typical rheumatoid nodulosis with follow-ups exceeding 25 years. Onset occurred at 14 and 22 years of age, respectively. Both patients presented with palindromic rheumatism, positive tests for rheumatoid factors, negative tests for other biological markers, and normal radiographs. Multiple subcutaneous nodules developed after 4 and 6 years with palindromic flares, respectively. Functional impairments and disfigurement required several surgical procedures to remove nodules. Histology was typical for rheumatoid nodules. Neither patient responded to disease-modifying anti-rheumatic drugs (gold, antimalarials, and D-penicillamine). Treatment consisted of nonsteroidal anti-inflammatory drugs combined with prednisone as needed. After 20 and 22 years of follow-up, respectively, both patients had typical rheumatoid arthritis with deformities and radiological joint destruction. In conclusion, these two cases establish that rheumatoid nodulosis can occur as a presentation of rheumatoid arthritis with a potential for severe joint damage after many years.

Anti-Inflammatory Agents, Non-Steroidal↗

Controlled plasmid gene transfer to murine renal carcinoma by hexadecylphosphocholine.

We report here that the anticancer drug hexadecylphosphocholine (HPC) can control plasmid DNA-mediated gene transfer to renal carcinoma following intratumoral administration. Significant improvement of gene expression levels could be achieved depending on HPC dose administered. Optimal concentration of HPC co-injected with plasmid DNA was found to be 0.2% (w/v) showing up to a 10-fold increase in reporter gene expression levels when compared to DNA administered alone. In vivo gene transfer activity of HPC was not affected by the nature of the diluent used, i.e. glucose-based or saline-based isotonic solutions. Although in vitro transfection activity of HPC formulations could not be evidenced, a liposome leakage assay revealed that HPC could significantly destabilize stable lipid membranes suggesting that a possible membrane permeation enhancer activity of HPC combined to the physical stress induced by the intratumor injection may facilitate plasmid DNA entry inside the cells resulting in increased gene expression. HPC/plasmid formulations represent new and attractive non-viral gene delivery systems with potential in cancer gene therapy and vaccination.

Animals↗

IgG reactivity with a 100-kDa tissue and endothelial cell antigen identified as topoisomerase 1 distinguishes between limited and diffuse systemic sclerosis patients.

We have analyzed antibody (Ab) reactivities of patients with limited systemic sclerosis (SSc) and anti-centromere Ab, patients with diffuse SSc and anti-topoisomerase 1 (anti-topo 1) Ab, patients with diffuse SSc without anti-topo 1 or anti-centromere Ab and age- and gender-matched healthy controls with normal human tissue and endothelial cell (EC) antigens. IgG reactivities with tissue antigens differed significantly between patients with anti-topo 1 Ab and patients with anti-centromere Ab. One 100-kDa band identified as topoisomerase 1 in macrovascular and microvascular EC extracts was recognized by IgG from patients with anti-topo 1 Ab and 50% of patients without specific Ab. IgG from patients with limited SSc and anti-centromere Ab, but not those of other patients or controls specifically recognized a 80-kDa band only in microvascular EC. Our results indicate that Ab from patients with limited or diffuse SSc with or without anti-topo 1 Ab exhibit specific and mutually exclusive reactivity patterns.

Autoantibodies↗

Making pregnancy safer for patients with lupus.

Systemic lupus erythematosus is a hormone-dependent disorder predominantly affecting young women in whom changes in hormonal activity affect the course of the disease. More specifically, pregnancy is associated in 50 to 60% of cases with a clinical flare manifesting as renal or hematological symptoms, usually during the second or third trimester but occasionally in the postpartal period. Patients should be strongly advised to start a pregnancy only if their disease has been stable for at least 6 months, and they should be informed of the few contraindications. Severe flares are uncommon (10%) and the risk of maternal death is now 2 to 3%. The risk of the fetus remains high, however. Thus, fetal loss is common, particularly in patients with a lupus anticoagulant, renal failure, or arterial hypertension. Preterm birth occurs in 25% to 50% of cases and intrauterine growth retardation in 30%. Neonatal lupus with or without congenital heart block is exceedingly rare, being seen in the 1% of SLE women who have anti-SSA (Ro) and/or SSB (La) antibodies. To ensure a favorable outcome for both the mother and the child, the pregnancy should be planned, started during a period of disease stability, monitored closely (physical examination, laboratory tests, and Doppler ultrasound), and treated as needed (with antimalarial therapy throughout the pregnancy). Even with these precautions, however, preterm birth remains common.

Birth Weight↗

Evaluating inflammatory joint disease: how and when can autoantibodies help?

The diagnosis of inflammatory joint disease rests on a constellation of symptoms, signs, laboratory test results and, occasionally, histological findings. Classification criteria have been developed by national learned societies, international panels of experts or, more rarely, an expert working alone. These criteria are intended to provide a common language for therapeutic trials and international publications. Yet, they are often inappropriately used as diagnostic tools for the individual patient. Identification of an early seroimmunologic marker with high sensitivity and specificity for classifying patients with recent-onset joint disease is a daunting challenge. Test performance characteristics such as sensitivity, specificity, positive and negative predictive values, and the positive or negative likelihood ratio help to assess the diagnostic usefulness of a laboratory test in a specific situation. The difference between the pretest and posttest likelihoods of obtaining a positive or negative result measures the usefulness, or performance, of a laboratory test in a specific situation according to the prevalence of the disease. A higher positive likelihood ratio indicates a more useful test. In a patient with inflammatory joint disease, the diagnosis can be sought by assaying a limited number of autoantibodies according to a decision tree. Thus, IgM rheumatoid factors (latex test or ELISA) and antibodies to filaggrin or other citrullinated proteins (antikeratin antibodies by indirect immunofluorescent assay or anticyclic citrullinated peptides by ELISA) identify more than 70% of cases of early rheumatoid arthritis with greater than 98% specificity. If these markers are negative, testing for antinuclear antibodies by indirect immunofluorescent assay on HEp-2 cells identifies 99% of cases of lupus and progressive systemic sclerosis. Confirmation of the diagnosis can be obtained by characterizing the autoantibodies: thus, presence of antidouble-stranded DNA (dsDNA, by the Farr radioimmunoassay, indirect immunofluorescent assay on Crithidia luciliae, or ELISA (IgG)) or of antinucleosome antibodies (ELISA) indicates lupus, whereas anticentromere, antitopoisomerase I (Scl 70), and antinucleolar antibodies point to progressive systemic sclerosis. A positive test for antibodies to soluble nuclear antigens of the U1 RNP type suggests mixed connective tissue disease or lupus but may indicate scleroderma. Anti-Sm antibodies are found in fewer than 10% of lupus patients but are highly specific. Anti-SSA (Ro) and anti-SSB (La) suggest lupus or primary Sjögren's syndrome. When tests are negative for ANA, several antibodies to cytoplasmic organelles are valuable diagnostic tools, such as anti-J01 for polymyositis syndromes and antiribosome antibodies for lupus, although their sensitivity is modest (20-25%). Finally antineutrophil cytoplasmic antibodies (ANCAs) ensure the diagnosis of small-vessel vasculitides, which often involve the lungs and kidneys. Thus, in diffuse Wegener's granulomatosis, ANCAs exhibiting the classic cytoplasmic pattern and corresponding by ELISA to anti-PR3 are found. In microscopic polyangiitis the ANCAs are peripheral and correspond by ELISA to antimyeloperoxidase antibodies. Tests for other antibodies are less often needed to evaluate inflammatory joint disease.

Antibodies, Antinuclear↗

Parvovirus B19 and autoimmune diseases.

Parvovirus B19 (B19) causes many clinical disorders, of which the most common are erythema infectiosum, aplastic crisis complicating chronic hemolytic anemia, and hydrops fetalis. In young adults, the skin eruption caused by B19 is accompanied with polyarthritis and polyarthralgia in 60% of the cases. The joint abnormalities predominate in the hands and feet and usually resolve within a week (range 2-21 d). Serological tests show IgM antibodies against B19, confirming the diagnosis of recent infection. Protracted polyarthritis occurs in some patients and seems associated with the DR4 histocompatibility alleles. Rheumatoid factors can be produced transiently in these patients. Other autoantibodies produced in the wake of B19 infection include anti-nuclear antibodies, anti-DNA, anti-SSA/SSB, and anti-phospholipids. Acute B19 infection can simulate early rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE) (lupus-like eruption over the cheeks, cytopenia, etc.). In addition, there have been a few reports of erosive RA or SLE developing shortly after a B19 infection, with positive PCR tests for B19 DNA in synovial tissue or blood cells. Studies in large series indicate that B19 is probably an extremely rare cause of RA or SLE. Vasculitides affecting the small vessels (Henoch-Schonlein purpura, Wegener's granulomatosis), medium-sized vessels (periarteritis nodosa), and large vessels (giant cell arteritis) can occur after B19 infection. Here again, the number of clinical cases is small.

Adolescent↗

JC virus leukoencephalopathy complicating Wegener's granulomatosis.

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the brain caused by the JC virus. It occurs in association with immunodepression due, for instance, to a hematological malignancy, HIV infection, or immunosuppressive therapy for an organ transplant or systemic disease. We describe the fourth reported case of PML in a patient receiving immunosuppressants for Wegener's granulomatosis. A 71-year-old woman receiving azathioprine and glucocorticoid therapy experienced onset of right-sided hemiplegia within a few days, became comatose, and died within a few days. MRI of the brain showed a subcortical lesion in the left parietal lobe generating low signal on T1 images and high signal on T2 images. The initial diagnosis was cerebral vasculitis. However, the postmortem examination showed PML. The diagnosis of PML rests on JC virus detection in the cerebrospinal fluid by PCR assay and on demonstration in a brain biopsy of the typical histological pattern with presence of the JC virus within the demyelinated lesions. No specific or effective treatments are available. Immunosuppressant drugs should be discontinued if possible.

Aged↗