Rheumatoid Arthritis: Saraux A

Pham T, Fautrel B, Gottenberg JE, Goupille P, Hachulla E, Masson C, Morel J, Mouthon L, Saraux A, Schaeverbeke T, Wendling D, Mariette X, Sibilia, Anonymous00011. · No affiliation provided · Joint Bone Spine. · Pubmed #18708020 No free full text.

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Berthelot JM, Blanchais A, Marhadour T, le Goff B, Maugars Y, Saraux A. · No affiliation provided · Joint Bone Spine. · Pubmed #19211288 No free full text.

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Devauchelle-Pensec V, Pers JO, Youinou P, Saraux A. · No affiliation provided · Rev Med Interne. · Pubmed #18403066 No free full text.

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Binard A, Devauchelle-Pensec V, Fautrel B, Jousse S, Youinou P, Saraux A. · No affiliation provided · Clin Exp Rheumatol. · Pubmed #17417982 No free full text.

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Youinou P, Daridon C, Saraux A, Devauchelle V, Pers JO. · No affiliation provided · Clin Exp Rheumatol. · Pubmed #17181915 No free full text.

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Youinou P, Pers JO, Saraux A, Pennec YL. · No affiliation provided · Clin Exp Immunol. · Pubmed #15958065 links to  free full text

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Pers JO, Le Pottier L, Devauchelle V, Saraux A, Youinou P. · Laboratoire d'immunologie, centre hospitalier universitaire de Brest, B.P. 824, 29609 Brest, France. · Rev Med Interne. · Pubmed #18403061 No free full text.

Abstract: INTRODUCTION: Sjögren's syndrome (SS) is an autoimmune epithelitis hallmarked by a disruption of epithelial cells, the subsequent lymphocytic infiltration of lachrymal and salivary glands (SGs), and their ensuing dryness. One may posit that SS is triggered by viruses, and/or modulated by sex steroid hormones, and there is indeed a consensus that its aetiology is multifactorial, with genetic factors interacting with environmental agents. CURRENT KNOWLEDGE AND KEY POINTS: T-cells have long occupied central stage of the debate on the type of lymphocytes involved in the pathogenesis of SS. The relevance of B cells has, however, been emphasized over the past five years and new insights into their functions revealed. Furthermore, increased levels of the B-cell activating factor (BAFF) may be responsible for quantitative and qualitative anomalies of B-cells found in SS such as emergence of self reactive B-cells. This review reports compelling evidence that B-cells are involved in the pathophysiology of SS. PROSPECTS: Since SS may thus be conceived as a model for B-cell-induced autoimmunity, it is no surprise that B-cell ablative-treatment has proven to be relatively effective in SS.

Youinou P, Devauchelle V, Hutin P, Le Berre R, Saraux A, Pers JO. · Department of Immunopathology, Brest University Medical School, Brest, France. · Clin Rev Allergy Immunol. · Pubmed #17992590 No free full text.

Abstract: Although the relative contributions of T cells and B cells in Sjögren's syndrome (SS) are far from being settled, recent studies have suggested a crucial role for B cells in its pathophysiology. Early investigations have focused on the ability of B cells to produce autoantibodies, and new studies have enlarged the range of their functions. For example, beyond the paradigm that T lymphocytes maintain strict control over B cells, the latter cells are now acknowledged to solicit their own help from the former cells and release a flurry of cytokines. Further, some of these B cells act as antigen-presenting cells. Increased levels of the B cell activating factor (BAFF) found in SS may be responsible for high numbers of circulating Bm2/Bm2' cells and associated functional abnormalities of B cells, such as a BAFF-induced increased expression of CD19, which decreases the required strength generated by antigen binding for transmitting its signal. This review reports compelling evidence that B cells are involved in the pathophysiology of SS. As this brings novel prospects for the treatment of the disease, it is no surprise that B cell ablative treatment has proven to be relatively efficacious in SS.

Daridon C, Guerrier T, Devauchelle V, Saraux A, Pers JO, Youinou P. · Laboratory of Immunology, Brest University Medical School Hospital, Brest, France. · Autoimmun Rev. · Pubmed #17643928 No free full text.

Abstract: Analysis of salivary glands of patients with primary Sjögren's syndrome has yielded conflicting results with respect to T helper (Th)1/Th2 polarization. This balance might parallel the progress of the local lesions. B-cells are now taking center stage in this disease. They can also be primed to differentiate into two cytokine-production pathways, dubbed B effector (Be) 1 and Be2 cells. This is discussed in the light of our recent finding that Be1 accompany Th1, while Be2 accompany in the tissue lesions.

Youinou P, Jamin C, Saraux A. · Laboratory of Immunology, Brest University Medical School Hospital, Brest, France. · Clin Exp Rheumatol. · Pubmed #17543163 No free full text.

Abstract: The interest for B-cells in rheumatoid arthritis (RA) is currently being revived. They are involved in the development and activation of lymphoid architecture by regulating dentritic cell and T-cell function through cytokine production. Receptor editing an revising are also essential in B-cells and aid in preventing autoimmunity. Abnormalities in the subset distribution and a default in any task assigned to the B-cells may favor autoimmunity. Beneficied responses to B-cell depletion in RA by anti-CD20 monoclonal antibody rituximab illustrate the importance of B-lymphocytes in the pathogenesis of this disease. A new avenue has thus been opened, whereby B-lymphocytes return as a significant contributor to autoimmune disorders.

Bosello S, Pers JO, Rochas C, Devauchelle V, De Santis M, Daridon C, Saraux A, Ferraccioli GF, Youinou P. · Laboratory of Immunology, Medical School, Brest, France. · Int J Immunopathol Pharmacol. · Pubmed #17346422 No free full text.

Abstract: Interest in B-cells has been revived due to the description of new functions. Supporting a role for B-cells in the genesis of autoimmune diseases is the fact that the B-cell activating factor of the TNF ligand family (BAFF) is essential in their physiology. However, in each disease, this is restricted to a subgroup of patients. Based on experiments in mice, and validated in humans, this new cytokine has been highlighted. Excessive production of BAFF alters immune tolerance by rescuing self-binding B-cells. Overexpression in mice leads to autoimmune manifestation, and BAFF levels are elevated in the serum of autoimmune patients. Similar abnormalities occur in chronic lymphocytic leukemia. Recent works suggest that antagonizing the protein (or competing for its receptors) is relevant to the treatment. Advances in our understanding of the BAFF system offers the opportunity to improve our therapeutic approach.

Renaudineau Y, Jamin C, Saraux A, Youinou P. · Brest University Medical School, Brest, France. · Autoimmunity. · Pubmed #15804700 No free full text.

Abstract: Rheumatoid factors (RF), which are antibodies (Ab) with specificity directed against gamma (?) globulins, are the commonest auto-Ab ever described in man. Some of them are referred to as agglutinating RF, others designated non-agglutinating RF. Not only do these characterize rheumatoid arthritis (RA), but they are also encountered in a variety of disease conditions, as well as a proportion of healthy controls. Although non-specific for RA, the measurement of agglutinating IgM-RF remains the most useful serological test for the diagnosis of this disease. Demonstration of abnormal amount of serum RF by any method for which the result has been positive in less than 5% of normal subjects has indeed become one of the seven revised criteria, listed by the American College of Rheumatology (Arnett, FC, Edworthy, SM, Bloch, DA, McShane, DJ, Fries, JF, Cooper, NS, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum, 1988: 31: 315-24), for the classification of RA. Over the course of years, the relative importance of genetic (Carson, DA, Chen, PP, Kipps, TJ, Radoux, V, Jirik, FR, Goldfien, RD, et al. Idiotypic and genetic studies of human rheumatoid factors. Arthritis Rheum, 1987: 30: 1321-1325) and environmental (Nemazee, DA, Sato, VL. Enhancing antibody, a novel component of the immune response. Proc Natl Acad Sci USA, 1982: 79: 3828-3832) factors in the production of such intriguing auto-Ab has been delineated.

Botton E, Saraux A, Laselve H, Jousse S, Le Goff P. · Service de rhumatologie, Hôpital de la cavale blanche, CHU Brest, 29609 Brest cedex, France. · Joint Bone Spine. · Pubmed #14563459 No free full text.

Abstract: Although bone and joint manifestations are common in children with cystic fibrosis (CF), they have received little attention in adults. As compared to healthy individuals, bone mineral density is low, even with calcium intakes greater than 1500 mg/d. Nevertheless, calcium and phosphate levels in blood and urine are often normal, and vitamin D levels vary. Short stature with a low body mass index and central hypogonadism are the rule in these patients. Fractures and kyphosis are often reported. CF arthropathy occurs in 2-8.5% of patients. Arthritis develops, and there may be skin eruptions. Non-steroidal antiinflammatory drug therapy is effective. Hypertrophic osteoarthropathy associated with respiratory failure is present in 2-7% of patients. Rheumatoid arthritis, spondyloarthropathies, sarcoidosis, and amyloidosis have been reported in association with CF. Knee pain due to patellofemoral syndrome, quinolone-induced arthropathy, and mechanical back pain have been described. Rheumatoid factor titers are higher than in healthy controls, particularly in patients with episodic arthritis. No data are available on antiperinuclear factor or antikeratin antibody titers. Tests for antinuclear antibody are usually negative. Circulating immune complex levels and antibodies to heat shock proteins may be elevated. Antineutrophil cytoplasmic antibody of the bactericidal/permeability-increasing protein (BPI) or azurocidin (AZ) type has been reported, often in high titers (up to 40%).

Devauchelle-Pensec V, Saraux A, Alapetite S, Colin D, Le Goff P. · Rheumatology Department (DC), Hĵpital de la Cavale Blanche, CHU Brest, BP 814, F 29609 Brest Cedex, France. · Joint Bone Spine. · Pubmed #12477226 No free full text.

Abstract: The extent to which radiographs of the hands and feet can contribute to the diagnosis of early rheumatoid arthritis (RA) has received little research attention. Yet, the workup for recent-onset inflammatory joint disease usually includes radiographs of the hands and feet. We reviewed the literature for data on the value of these radiographs for diagnosing early RA. We sought to determine whether radiographic changes in the hands and feet constitute a valid diagnostic criterion, i.e., show good discrimination, good reproducibility, and an ability to detect early disease. Furthermore, we evaluated whether the sensitivity, specificity, and positive and negative predictive values of these changes could be calculated from published data. Few cohort studies of early inflammatory joint disease have been published, and the data come mainly from studies in early RA. Among radiographic alterations described to date, erosions seem associated with the best reliability and discriminating power. Radiographic alterations are of limited sensitivity for early rheumatoid arthritis because they occur only after some time. Radiographs of the hands and feet are far easier to obtain than magnetic resonance imaging and ultrasonography, which seem promising but are still undergoing validation.

Berthelot JM, Saraux A, Maugars Y, Prost A, Le Goff P. · Rheumatology Department, Brest Teaching Hospital, France. · Rev Rhum Engl Ed. · Pubmed #10339779 No free full text.

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Saraux A, Le Goff P. · Rheumatology Department, La Cavale Blanche Teaching Hospital, Brest, France. · Rev Rhum Engl Ed. · Pubmed #10084164 No free full text.

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Devauchelle-Pensec V, Pennec Y, Morvan J, Pers JO, Daridon C, Jousse-Joulin S, Roudaut A, Jamin C, Renaudineau Y, Roué IQ, Cochener B, Youinou P, Saraux A. · Hôpital de la Cavale Blanche, CHU Brest, France. · Arthritis Rheum. · Pubmed #17330280 links to  free full text

Abstract: OBJECTIVE: There is evidence to support a dominant role for B cells in the pathophysiology of primary Sjögren's syndrome (SS). Therefore, we evaluated the safety and efficacy of anti-CD20 monoclonal antibody. METHODS: Sixteen patients who met the new American-European Consensus Group criteria for primary SS and scored >50 on at least 2 of 4 visual analog scales (VAS; 100 mm) evaluating global disease, pain, fatigue, and global dryness received infusions of low-dose rituximab (375 mg/m(2)) at weeks 0 and 1 without steroid premedication. RESULTS: Slow rituximab infusions (100 mg/hour) were well tolerated, with only 1 patient experiencing serum sickness-like disease. There was a dramatic reduction in B cells of the blood and salivary gland (SG). At week 12, VAS scores with respect to fatigue and dryness (P < 0.05), tender point count (P < 0.035), and quality of life as evaluated by the Short Form 36 questionnaire (SF-36; P < 0.001) were significantly improved. At week 36, significant improvements were noted in the 4 VAS scores (P < 0.05), tender joint count (P = 0.017), tender point count (P = 0.027), and SF-36 (P < 0.03). Pulmonary manifestations were ameliorated in 1 patient. Patients with improvements on at least 3 of the 4 VAS scores at any visit (n = 11) had a shorter disease duration than the other patients (n = 5; mean +/- SD duration 3.8 +/- 5.4 versus 30.1 +/- 29.5 years; P = 0.02). CONCLUSION: Low-dose rituximab infusions were well tolerated without the benefit of steroids. Infusions induced a rapid depletion of B cells in the blood and SG and could improve primary SS. Controlled studies are needed.

Martinot M, Sordet C, Soubrier M, Puéchal X, Saraux A, Lioté F, Guggenbuhl P, Lègre V, Jaulhac B, Maillefert JF, Zeisel M, Coumaros G, Sibilia J. · Service de Pathologies Infectieuses et Tropicales, Médicale A - Hôpitaux Universitaires de Strasbourg and Service de Médecine Interne et de Rhumatologie, Hopital Pasteur, Colmar, France. · Clin Exp Rheumatol. · Pubmed #15971417 No free full text.

Abstract: OBJECTIVE: To determine the diagnostic value of serum and synovial procalcitonin (PCT) for bacterial arthritis and to determine the cellular origin of synovial PCT. METHODS: A prospective study enrolled 42 patients with acute arthritis including 11 bacterial arthritis, 18 rheumatoid arthritis and 13 crystal induced arthritis. Diagnostic values of serum and synovial PCT levels were determined by a immunoluminometric assay (Lumitest PCT) and compared to those of classical inflammatory markers (C-reactive protein, erythrocyte sedimentation rate, synovial fluid cellularity and both serum and synovial IL-6 and TNF alpha). Using fibroblast-like synoviocyte (FLS) cultures derived from rheumatoid arthritis (n = 4) and osteo-arthritis (n = 3) synovium, with or without stimulation by lipopolysaccharid or recombinant streptococcal protein 1/II, we attempted to determine whether synovial cells could be a source of PCT. RESULTS: Serum PCT was the best parameter to distinguish patients with acute bacterial arthritis from patients with crystal induced arthritis or rheumatoid arthritis. In setting of an acute arthritis serum PCT (> 0.5 ng/mL) achieved 55% sensitivity and 94% specificity for the diagnosis of bacterial arthritis, while CRP (> 50 mg/L) had 100% sensitivity but poor specificity (40%). Serum PCT appeared to be higher in patients with septic arthritis resulting from "systemic infection" than in cases resulting from direct inoculation. Synovial PCT was not useful to discriminate between infectious and non infectious arthritis in clinical practice. PCT could not be detected at significant levels in the conditioned medium from fibroblast-like synoviocyte cultures. CONCLUSION: Serum PCT is a poorly sensitive but specific marker of bacterial arthritis. Use of serum PCT in association with CRP could nevertheless be useful in an emergency situation for the diagnosis of bacterial arthritis.

Devauchelle Pensec V, Saraux A, Berthelot JM, Alapetite S, Jousse S, Chales G, Thorel JB, Hoang S, Nouy-Trolle I, Martin A, Chiocchia G, Youinou P, Le Goff P. · Unit of Rheumatology and the Laboratory of Immunology, Hôpital de la Cavale Blanche, CHU Brest, Brest, France. · J Rheumatol. · Pubmed #14705220 No free full text.

Abstract: OBJECTIVE: In a cohort of patients with early arthritis, to evaluate how well foot radiographs at study inclusion predicted a diagnosis of rheumatoid arthritis (RA) 2 years later. METHODS: A cohort of patients with arthritis of less than one year duration was evaluated in a multicenter study and followed for 30 +/- 11 months. An observer blinded to patient data read all 149 hand and foot radiographs done at study inclusion, using item 7 of the 1987 American College of Rheumatology (ACR) criteria for RA and Sharp's method to score erosions and joint space narrowing. RESULTS: The kappa coefficient for the 1987 ACR item 7 was 0.52 for bony decalcification and 0.87 for erosions. Intra and interobserver correlation coefficients for Sharp's scores ranged from 0.90 to 0.98. Erosions at the feet were significantly associated with RA. The item 7 erosion component at the feet was more specific than the full item 7 (97.5% vs 94%; p = 0.01). Sharp's erosion score at the feet was not better than the erosion component of item 7 (sensitivity 18%; specificity 97.5%). Combined use of radiographs of the hands and feet improved the diagnostic performance of the item 7 erosion component; (sensitivity and specificity of item 7 erosions at the hands combined with the feet were 32.5% and 94.5%, respectively). CONCLUSION: The "erosion" criterion at the feet had the best diagnostic performance and was significantly associated with a diagnosis of RA. Combining hand and foot radiographs improved diagnostic performance.

Pham T, Claudepierre P, Constantin A, Fautrel B, Gossec L, Gottenberg JE, Goupille P, Hachulla E, Masson C, Morel J, Saraux A, Schaeverbeke T, Wendling D, Mariette X, Sibilia J. · Service de Rhumatologie, CHU Conception, Marseille, France. · Joint Bone Spine. · Pubmed #19560051 No free full text.

Abstract: OBJECTIVES: To elaborate a how-to-use abatacept material intended to help physicians in the management of patients with inflammatory diseases treated with this drug in routine practice. METHODS: 1) Selection of the relevant domains by a rheumatologists' panel; 2) Search for published evidence in each domain; 3) Elaboration of the clinical tool guide with a 3-level gradation of evidence (evidence-based medicine EBM, official recommendations and expert's opinion). The experts were 11 academic rheumatologists with a large experience in prescribing abatacept and in managing rheumatoid arthritis. They were all members of the CRI (Club Rhumatismes et Inflammation), a section of the French Rheumatology Society dedicated to the inflammatory rheumatic diseases. Each fact sheet was reviewed by two other experts; 4) Regular updating based on medical literature and postmarketing surveillance data. RESULTS: Four domains were considered relevant: abatacept contraindications, management of side effects or associated diseases appearing during abatacept treatment, management of "practical situations" such as surgery or pregnancy, physician and patient information. After the literature analysis and discussion during an experts' meeting, a consensus was reached on: a pre-treatment checklist aimed at searching abatacept contraindications; a what-to-do document when facing side effects or associated diseases (autoimmune pathology, bacterial or viral infections, cardiovascular diseases, intolerance to abatacept, solid or haematological malignancy) or "practical situations" (surgery, pregnancy, vaccination, travel, drug-drug interactions); an example of standard information letter to be addressed to the attending physician (rheumatologist and general practitioner); an example of standard information letter to be addressed to the patient. CONCLUSION: Based on both an EBM approach and an expert's opinion approach, this abatacept clinical tool guide should provide assistance to all physicians attending patients treated with abatacept. For a better implementation in clinical practice, this tool guide will be available online at www.cri-net.com and regularly updated.

Guennoc X, Narbonne V, Jousse-Joulin S, Devauchelle-Pensec V, Dougados M, Daurès JP, Saraux A. · Rheumatology Unit and Immunology Department, Brest Teaching Hospital, F 29609 Brest Cedex, France. · J Rheumatol. · Pubmed #19531755 No free full text.

Abstract: OBJECTIVE: To evaluate the seroprevalence of hepatitis B (HBV) and C (HCV) in patients living in France with recent-onset polyarthritis suggesting rheumatoid arthritis. METHODS: The 813 patients in the ESPOIR cohort were screened for anti-HCV antibodies and HBs antigen. RESULTS: Seroprevalence was 0.86% for HCV (n = 7) and 0.12% for HBV (n = 1). HCV-related arthritis was diagnosed in 4 (0.5%) patients; no patient had HBV-related arthritis. HCV-seropositive patients had significantly higher transaminase levels (ALAT, 41.5 IU vs 23.2 IU, p = 0.02; and ASAT, 39.2 IU vs 21.8 IU, p = 0.001) but only 2 patients had ASAT or ALAT levels > 40 IU. No significant differences were found for anti-CCP antibodies, C-reactive protein, erythrocyte sedimentation rate, or other test. HCV seroprevalence was significantly higher in the subgroup with history of blood transfusion than in other patients (3.7% vs 0.42%, p = 0.02). Two of the 7 HCV positive patients and the single patient with confirmed hepatitis B infection were born in areas with higher prevalence of viral hepatitis (Togo, Senegal, Vietnam). Positive hepatitis status was known before study inclusion in 4 of the 7 HCV-positive patients and in the HBV-positive patient. CONCLUSION: The prevalence of HBV and HCV in a population of patients with recent-onset polyarthritis suggestive of RA was not greater than expected based on data from the general population in the same geographic area. Routine HBV and HCV serological testing did not contribute substantially to the diagnosis of recent-onset polyarthritis. Although advisable before initiating immunosuppressive or hepatotoxic drugs, serological testing for HCV and HBV is unnecessary in routine diagnostic evaluation of recent-onset polyarthritis.

Rochas C, Hillion S, Saraux A, Mageed RA, Youinou P, Jamin C, Devauchelle V. · Université Européenne de Bretagne, Université de Brest, IFR 148 ScInBioS, and Laboratory of Immunology, Centre Hospitalier Universitaire, Brest Hôpital Morvan and Cavale Blanche, Brest, France. · Arthritis Rheum. · Pubmed #19404965 No free full text.

Abstract: OBJECTIVE: B cells that accumulate in the synovial tissue of rheumatoid arthritis (RA) patients revise their receptors due to coordinate expression of recombination-activating gene 1 (RAG-1) and RAG-2 genes. The aim of this study was to determine the mechanisms that control this re-expression. METHODS: B cells from healthy control subjects were cocultured with fibroblast-like synoviocytes (FLS) from patients with RA and osteoarthritis (OA). Re-expression of RAG messenger RNA (mRNA) and proteins was analyzed by reverse transcription-polymerase chain reaction (RT-PCR) and indirect immunofluorescence. Activity of RAG enzymes was evaluated by flow cytometry to measure variations in immunoglobulin kappa and lambda light chain expression and by ligation-mediated-PCR to assess specific DNA breaks. Blocking antibodies, short hairpin RNA, and recombinant cytokine were used to identify the molecules involved in RAG re-expression. RESULTS: RA FLS, but not OA FLS, induced B cells to re-express RAG mRNA and proteins. Enzymes were functional, since the kappa-to-lambda ratios decreased and specific DNA breaks were detectable after coculture with RA FLS. Transmembrane BAFF provided the first signal of RAG re-expression, since its down-regulation in RA FLS prevented RAG gene transcription in B cells. The failure of transmembrane BAFF from OA FLS to induce RAG suggests that a second signal was provided by RA FLS. Interleukin-6 (IL-6) is a candidate, since blockade of its receptors precluded transcription of RAG genes by RA FLS. Unless supplemented with IL-6, OA FLS were unable to induce RAG gene expression in normal B cells. CONCLUSION: Two independent signals are required for the induction of RAG gene expression in B cells that infiltrate the synovium of patients with RA.

Fautrel B, Guillemin F, Meyer O, de Bandt M, Berthelot JM, Flipo RM, Lioté F, Maillefert JF, Wendling D, Saraux A, Combe B, Le Loët X, Anonymous00044, Anonymous00045, Anonymous00046. · Department of Rheumatology, Groupe Hospitalier Pitié-Salpêtrière, Paris, France. · Arthritis Rheum. · Pubmed #19333993 No free full text.

Abstract: OBJECTIVE: To survey rheumatologists' preferences for the choice of a second-line disease-modifying antirheumatic drug (DMARD) after inadequate response with methotrexate (MTX) therapy in rheumatoid arthritis (RA). METHODS: Thirty-six rheumatologists stated their preferences for RA treatment after inadequate response with MTX therapy (optimal dose at least 6 months). From the initial scenario, we derived 54 vignettes varying by rheumatoid factor or anti-cyclic citrullinated peptide antibody presence, swollen joint count, Disease Activity Score in 28 joints, and structural damage. Respondents stated their preference among 5 therapeutic options: MTX continuation, switch to another conventional DMARD, addition of another conventional DMARD, addition of anakinra, or addition of a tumor necrosis factor (TNF) blocker. Presentation by pairs yielded 10 combinations of strategies for each variant, totaling 540 vignettes; participants evaluated a random sample of 180 vignettes. Determinants of each top-ranked option were analyzed by logistic regression. The compilation of these data served to define a therapeutic algorithm. RESULTS: The responses of 33 rheumatologists were analyzable. Therapeutic preferences corresponded to the top-ranked options. For patients with mild or moderately active RA, either a switch or step-up strategy to another conventional DMARD was top ranked. TNF blockers were preferred for RA patients with high disease activity or progressive structural damage. On the basis of these preferences, we developed a simple decision tree for use in daily clinical practice. CONCLUSION: Our simple, easy-to-use decision tree developed from rheumatologists' preferences for therapy after failure of MTX therapy in RA treatment may guide rheumatologists in daily practice to choose a second-line DMARD.

Le Pottier L, Devauchelle V, Fautrel A, Daridon C, Saraux A, Youinou P, Pers JO. · Equipe d'Accueil 2216 and Institut Fédératif de Recherche 418, Science et Ingénierie en Biologie-Santé, Université de Brest, Brest, and Université Européenne de Bretagne, Brest, France. · J Immunol. · Pubmed #19265132 No free full text.

Abstract: This study reports on the characterization of B cells of germinal center (GC)-like structures infiltrating the salivary glands (SGs) of patients with Sjögren's syndrome. Eight two-color combinations were devised to characterize the phenotype of these B cells in 11 SG specimens selected from biopsies obtained from 40 Sjögren's syndrome patients and three normal tonsils. The 9G4 mAb, which recognizes V4.34-encoded autoAbs, enabled us to identify autoreactive B cells. Quantitative RT-PCR was used to determine the level of mRNAs for activation-induced cytidine deaminase (AICDA), repressors and transcription factors. CD20(+)IgD(-)CD38(+)CD21(+)CD24(-) B cells, similar to those identified in tonsil GCs, were seen in the SGs of four patients and, and since they expressed AICDA, they were termed "real GCs". CD20(+)IgD(+)CD38(-)CD21(+)CD24(+) B cells, seen in aggregates from the remaining seven samples, were characteristically type 2 transitional B cells and marginal zone-type B cells. They lacked AICDA mRNAs and were termed "aggregates". Real GCs from SGs contained mRNAs for Pax-5 and Bcl-6, like tonsil GC cells, whereas aggregates contained mRNAs for Notch-2, Blimp-1, IRF-4, and BR3, similar to marginal zone B cells. Further experimental data in support of this dichotomy included the restriction of CXCR5 expression to real GC cells, while sphingosine 1-phosphate receptor 1 was expressed only in aggregates. In contrast, both types of B cell clusters expressed the idiotype recognized by the 9G4 mAb. Our data indicate that, in SGs, a minority of B cell clusters represent genuine GC cells, while the majority manifest features of being type 2 transitional B cells and marginal zone cells. Interestingly, both types of B cell aggregates include autoreactive B cells.

Anonymous00075, Devauchelle-Pensec V, Josseaume T, Samjee I, Dougados M, Combe B, Saraux A. · Brest Teaching Hospitals, Brest, France. · Arthritis Rheum. · Pubmed #19035426 No free full text.

Abstract: OBJECTIVE: To assess the usefulness of using oblique foot radiographs in addition to posteroanterior radiographs of the hands and feet for detecting erosions in patients with recent-onset arthritis. METHODS: We included 813 patients from the prospective French ESPOIR cohort with arthritis of <6 months' duration and >or=2 swollen joints. Baseline standardized posteroanterior radiographs of the hands and feet and oblique radiographs of the feet were assessed by 2 blinded readers for erosions typical for rheumatoid arthritis (ETRA) and the Sharp score as modified by van der Heijde. RESULTS: A total of 715 complete sets were available. Mean +/- SD total Sharp scores were 3.6 +/- 6.6, 2.5 +/- 6.3, and 1.8 +/- 5 for the hand and wrist, foot, and oblique foot, respectively. ETRA were visible in 160 (22.4%) of 715 patients (95% confidence interval [95% CI] 19.4-25.6). They were seen on hand radiographs in 86 (53.7%) of 160 patients (95% CI 45.7-61.6), on posteroanterior foot radiographs in 91 (56.9%) of 160 patients (95% CI 48.8-64.6), and on oblique foot radiographs in 84 (52.5%) of 160 patients (95% CI 44.5-60.4). ETRA were visible at the feet, but not at the hands, in 74 (46%) of 160 patients (95% CI 38.4-54.3), among whom 22 (30%) had erosions only on the posteroanterior view, 16 (21%) only on the oblique view, and 36 (48.6%) on both. CONCLUSION: ETRA were found in 22.4% of patients. Adding an oblique foot radiograph identified 16 (10%) of 160 additional patients (95% CI 6-16), compared with 27.5% and 13.8% identified by adding posteroanterior radiographs of the hands and feet, respectively.