Emilio Martín-Mola

Hospital Universitario La Paz, Madrid, Madrid, Spain

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Publications (118)665.84 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective The ability to interpret scores from Patient Reported Outcome Measures at the individual patient level depends on the availability of valid, clinically meaningful benchmarks of response and state-attainment. The goal was to develop multinational estimates for Minimal Clinically Important Improvement (MCII) and Patient Acceptable Symptomatic State (PASS). Methods A multinational sample of patients with osteoarthritis (OA), were evaluated before and 4 weeks after treatment with nonsteroidal anti-inflammatory drugs. Patients completed either the Western Ontario and McMaster (WOMAC) NRS3.1 Index (hip and knee OA) or the Australian/Canadian (AUSCAN) NRS3.1 Index (hand OA) before and after treatment. Patients rated the clinical importance of their response to treatment and their satisfaction with the health state achieved from which multinational MCII and PASS estimates were calculated for both the WOMAC and AUSCAN Indices. A total of 609 patients from 7 countries participated in the study. MCII and PASS estimates varied slightly by instrument and subscale. Absolute (and percentage) change for MCII ranged between 6 to 9 (10% to 17%) for WOMAC and 4 to 9 (8% to 15%) for AUSCAN. PASS estimates ranged from 39 to 48 for WOMAC and 38 to 45 for AUSCAN. Some between-country variation was observed in MCII and PASS. Conclusion Preliminary multinational estimates for MCII and PASS have been developed for several countries. Further research is required to evaluate the robustness, temporal consistency and age- and gender-dependency of the preliminary estimates as well as their generalizability to other countries, languages, cultures, regions and other condition-specific outcome measures. This article is protected by copyright. All rights reserved. Copyright © 2014 American College of Rheumatology.
    Arthritis care & research. 01/2015;
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    ABSTRACT: The aim of this study was to establish guidelines for the optimization of biologic therapies for health professionals involved in the management of patients with RA, AS and PsA. Recommendations were established via consensus by a panel of experts in rheumatology and hospital pharmacy, based on analysis of available scientific evidence obtained from four systematic reviews and on the clinical experience of panellists. The Delphi method was used to evaluate these recommendations, both between panellists and among a wider group of rheumatologists. Previous concepts concerning better management of RA, AS and PsA were reviewed and, more specifically, guidelines for the optimization of biologic therapies used to treat these diseases were formulated. Recommendations were made with the aim of establishing a plan for when and how to taper biologic treatment in patients with these diseases. The recommendations established herein aim not only to provide advice on how to improve the risk:benefit ratio and efficiency of such treatments, but also to reduce variability in daily clinical practice in the use of biologic therapies for rheumatic diseases. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Rheumatology.
    Rheumatology (Oxford, England) 12/2014; · 4.44 Impact Factor
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    ABSTRACT: IntroductionCirculating CD4 T cells expressing CXCR5, ICOS and/or PD-1 are counterparts of follicular helper T cells (Tfh). There are three subpopulations of circulating Tfh (cTfh): CXCR5¿+¿CXCR3¿+¿CCR6- (Tfh-Th1), CXCR5¿+¿CXCR3-CCR6- (Tfh-Th2) and CXCR5¿+¿CXCR3-CCR6+ (Tfh-Th17). Our objective was to study the B cell helping capacity of cTfh subsets, and examine their frequency in Rheumatoid Arthritis (RA) patients, together with the frequency of circulating plasmablasts (CD19¿+¿CD20-CD38high).Methods Peripheral blood was drawn from RA patients with active disease (RA-a, DAS28¿>¿2.6) (n¿=¿17), RA in remission (RA-r, DAS28¿<¿2.6) (n¿=¿17) and healthy controls (HC) (n¿=¿34). cTfh and plasmablast frequencies were determined by flow cytometry. Cocultures of sorted CD4¿+¿CXCR5+ T cell subpopulations were established with autologous CD19¿+¿CD27- naïve B cells of HC, and concentrations of IgG, A and M were measured in supernatants.ResultsIsolated Tfh-Th2 and Tfh-Th17 but not Tfh-Th1 cells, induced naïve B cells to secrete IgG and IgA. The frequency of CXCR5+ cells gated for CD4+ T cells was not different among HC, RA-a and RA-r. In contrast, both RA-a and RA-r patients demonstrated an increased frequency of CD4¿+¿CXCR5¿+¿ICOS+ T cells and augmented (%Tfh-Th2¿+¿%Tfh-Th17)/%Tfh-Th1 ratio as compared with HC. In addition, RA-a but not RA-r patients, showed an increased frequency of circulating plasmablasts.Conclusion Both RA-a and RA-r patients demonstrate an increased frequency of cTfh and overrepresentation of cTfh subsets bearing a B cell helper phenotype, suggesting that altered germinal center dynamics play a role in RA pathogenesis. In contrast, only RA-a patients show an increased proportion of circulating plasmablasts.
    Arthritis Research & Therapy 12/2014; 16(6):500. · 4.12 Impact Factor
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    ABSTRACT: We assessed the effects of reduction and withdrawal of treatment in patients with rheumatoid arthritis who had a remission while receiving etanercept-plus-methotrexate therapy.
    New England Journal of Medicine 11/2014; 371(19):1781-92. · 54.42 Impact Factor
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    ABSTRACT: Follicular helper T cells (Tfh), localized in lymphoid organs, promote B cell differentiation and function. Circulating CD4 T cells expressing CXCR5, ICOS and/or PD-1 are counterparts of Tfh. Three subpopulations of circulating CD4+CXCR5+ cells have been described: CXCR3+CCR6- (Tfh-Th1), CXCR3-CCR6+ (Tfh-Th17), and CXCR3-CCR6- (Tfh-Th2). Only Tfh-Th17 and Tfh-Th2 function as B cell helpers. Our objective was to study the frequencies of circulating Tfh (cTfh), cTfh subsets and plasmablasts (CD19+CD20-CD27+CD38high cells), and the function of cTfh cells, in patients with Ankylosing Spondylitis (AS). To this end, peripheral blood was drawn from healthy controls (HC) (n = 50), AS patients naïve for TNF blockers (AS/nb) (n = 25) and AS patients treated with TNF blockers (AS/b) (n = 25). The frequencies of cTfh and plasmablasts were determined by flow cytometry. Cocultures of magnetically sorted CD4+CXCR5+ T cells with autologous CD19+CD27- naïve B cells were established from 3 AS/nb patients and 3 HC, and concentrations of IgG, A and M were measured in supernatants. We obseved that AS/nb but not AS/b patients, demonstrated decreased frequencies of circulating CD4+CXCR5+ICOS+PD-1+ cells and plasmablasts, together with a decreased (Tfh-Th17+Tfh-Th2)/Tfh-Th1 ratio. The amounts of IgG and IgA produced in cocultures of CD4+CXCR5+ T cells with CD19+CD27- B cells of AS/nb patients were significantly lower than observed in cocultures established from HC. In summary, AS/nb but not AS/b patients, demonstrate a decreased frequency of cTfh and plasmablasts, and an underrepresentation of cTfh subsets bearing a B helper phenotype. In addition, peripheral blood CD4+CXCR5+ T cells of AS/nb patients showed a decreased capacity to help B cells ex vivo.
    PLoS ONE 09/2014; 9(9):e107086. · 3.53 Impact Factor
  • C. Plasencia, D. Pascual-Salcedo, P. Alcozer, S. Garcia-Carazo, K. N. Franco, D. Cajigas, G. Bonilla, L. Lojo, L. Nuno, A. Villalba, D. Peiteado, F. Arribas, M. T. Lopez-Casla, E. Martin-Mola, A. Balsa
    Annals of the Rheumatic Diseases 01/2014; 72(Suppl 3):A428-A428. · 9.27 Impact Factor
  • Annals of the Rheumatic Diseases 01/2014; 71(Suppl 3):662-662. · 9.27 Impact Factor
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    ABSTRACT: Chinese translation Many patients with rheumatoid arthritis (RA) do not achieve adequate and safe responses with disease-modifying antirheumatic drugs (DMARDs). Tofacitinib is a novel, oral, Janus kinase inhibitor that treats RA. To evaluate the efficacy and safety of tofacitinib in combination with nonbiologic DMARDs. 1-year, double-blind, randomized trial (ClinicalTrials.gov: NCT00856544). 114 centers in 19 countries. 792 patients with active RA despite nonbiologic DMARD therapy. Patients were randomly assigned 4:4:1:1 to oral tofacitinib, 5 mg or 10 mg twice daily, or placebo advanced to tofacitinib, 5 mg or 10 mg twice daily. Primary end points were 20% improvement in American College of Rheumatology (ACR20) criteria; Disease Activity Score for 28-joint counts based on the erythrocyte sedimentation rate (DAS28-4[ESR]) of less than 2.6; DAS28-4(ESR)-defined remission, change in Health Assessment Questionnaire Disability Index (HAQ-DI) score, and safety assessments. Mean treatment differences for ACR20 response rates (month 6) for the 5-mg and 10-mg tofacitinib groups compared with the combined placebo groups were 21.2% (95% CI, 12.2% to 30.3%; P < 0.001) and 25.8% (CI, 16.8% to 34.8%; P < 0.001), respectively. The HAQ-DI scores (month 3) and DAS28-4(ESR) less than 2.6 response rates (month 6) were also superior in the tofacitinib groups versus placebo. The incidence rates of serious adverse events for patients receiving 5-mg tofacitinib, 10-mg tofacitinib, or placebo were 6.9, 7.3, or 10.9 events per 100 patient-years of exposure, respectively. In the tofacitinib groups, 2 cases of tuberculosis, 2 cases of other opportunistic infections, 3 cardiovascular events, and 4 deaths occurred. Neutrophil counts decreased, hemoglobin and low- and high-density lipoprotein cholesterol levels increased, and serum creatinine levels had small increases in the tofacitinib groups. Placebo groups were smaller and of shorter duration. Patients received primarily methotrexate. The ability to assess drug combinations other than tofacitinib plus methotrexate was limited. Tofacitinib improved disease control in patients with active RA despite treatment with nonbiologic DMARDs, primarily methotrexate. Pfizer.
    Annals of internal medicine 08/2013; 159(4):253-61. · 16.10 Impact Factor
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    ABSTRACT: Anti-TNF drugs have proven to be effective against Spondyloarthritis (SpA), although 30% of patients fail to respond or experience adverse events leading to treatment discontinuation. In rheumatoid arthritis, the presence of anti-drug antibodies (ADA) against the first TNF inhibitor influences the outcome after switching. Our aim was to assess whether the response to a second anti-TNF is related to the previous development of ADA to the first anti-TNF drug in SpA patients. Forty two SpA patients began a second anti-TNF drug after failing to respond to the first anti-TNF. Clinical activity was assessed by Ankylosing Spondylitis Disease Activity Score (ASDAS) at baseline (at the beginning of the 1st and 2nd anti-TNF) and at 6 months after switching. The drug and ADA levels were measured by ELISA before each administration. All patients were treated with anti-TNF drugs and mainly due to inefficacy were switched to a second anti-TNF. Out of 42 patients, 11 (26.2%) developed ADA during the first biologic treatment. At baseline, no differences in ASDAS were found in patients with or without ADA to the first (3.52 +/- 1.03 without ADA vs 3.14 +/- 0.95 with ADA, P=0.399) and to the second (3.36 +/- 0.94 without ADA vs 3.09 +/- 0.91 with ADA, P=0.466) anti-TNF. At 6 months after switching, patients with previous ADA had lower disease activity (1.62 +/- 0.93 with ADA vs 2.79 +/- 1.01 without ADA, P=0.002) and most patients without ADA had high disease activity state by the ASDAS (25 out of 31 (80.6%) without ADA vs 3 out of 11 (27.3%) with ADA, P=0.002). In SpA, the failure to respond to the first anti-TNF drug due to the presence of ADA predicts a better clinical response to a second anti-TNF drug.
    Arthritis research & therapy 07/2013; 15(4):R79. · 4.12 Impact Factor
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    ABSTRACT: Changes of the bone formation marker PINP correlated positively with improvements in vertebral strength in men with glucocorticoid-induced osteoporosis (GIO) who received 18-month treatment with teriparatide, but not with risedronate. These results support the use of PINP as a surrogate marker of bone strength in GIO patients treated with teriparatide. INTRODUCTION: To investigate the correlations between biochemical markers of bone turnover and vertebral strength estimated by finite element analysis (FEA) in men with GIO. METHODS: A total of 92 men with GIO were included in an 18-month, randomized, open-label trial of teriparatide (20 μg/day, n = 45) and risedronate (35 mg/week, n = 47). High-resolution quantitative computed tomography images of the 12th thoracic vertebra obtained at baseline, 6 and 18 months were converted into digital nonlinear FE models and subjected to anterior bending, axial compression and torsion. Stiffness and strength were computed for each model and loading mode. Serum biochemical markers of bone formation (amino-terminal-propeptide of type I collagen [PINP]) and bone resorption (type I collagen cross-linked C-telopeptide degradation fragments [CTx]) were measured at baseline, 3 months, 6 months and 18 months. A mixed-model of repeated measures analysed changes from baseline and between-group differences. Spearman correlations assessed the relationship between changes from baseline of bone markers with FEA variables. RESULTS: PINP and CTx levels increased in the teriparatide group and decreased in the risedronate group. FEA-derived parameters increased in both groups, but were significantly higher at 18 months in the teriparatide group. Significant positive correlations were found between changes from baseline of PINP at 3, 6 and 18 months with changes in FE strength in the teriparatide-treated group, but not in the risedronate group. CONCLUSIONS: Positive correlations between changes in a biochemical marker of bone formation and improvement of biomechanical properties support the use of PINP as a surrogate marker of bone strength in teriparatide-treated GIO patients.
    Osteoporosis International 06/2013; · 4.04 Impact Factor
  • Annals of the rheumatic diseases 06/2013; · 9.27 Impact Factor
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    ABSTRACT: BACKGROUND: Calprotectin is potentially a more sensitive biomarker of disease activity in rheumatoid arthritis (RA) than conventional acute-phase proteins such as the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) because it directly reflects inflammation in the synovium and synovial fluid rather than systemic inflammatory activity. OBJECTIVE: The aim of this study was to evaluate relationships between serum calprotectin levels, disease activity, and response to treatment. Calprotectin was also investigated as a predictive marker of clinical response. METHODS: This observational study included selected cohorts of patients with RA treated at La Paz University Hospital, Madrid, Spain. Associations between serum calprotectin levels and clinical and laboratory parameters were analyzed in a cross-sectional cohort of 60 patients with varying disease activity, and changes in calprotectin levels in response to treatment with infliximab were analyzed at baseline and after 3 and 6 months of treatment in a longitudinal cohort of 20 patients with very active disease. RESULTS: In the cross-sectional cohort, calprotectin levels correlated with rheumatoid factor levels (r = 0.25; p < 0.05) but not with titers of antibodies to cyclic citrullinated peptide. Significant correlations were also observed between calprotectin levels and the 28 swollen joint count (28-SJC), Disease Activity Score based on a 28-joint count (DAS28), Simplified Disease Activity Index (SDAI), ESR, and CRP levels. In the longitudinal cohort, calprotectin levels at baseline were not predictive of response to treatment but significantly decreased during treatment in responders (p < 0.0001). CONCLUSION: Calprotectin levels strongly correlate with clinical and laboratory assessments of joint inflammation and also decrease in response to treatment, indicating that calprotectin is a promising marker for assessment and monitoring of disease activity in patients with RA. Investigations are required to further evaluate its diagnostic, prognostic, and therapeutic potential.
    Molecular Diagnosis & Therapy 01/2013; · 2.59 Impact Factor
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    ABSTRACT: Data on treatment of glucocorticoid-induced osteoporosis (GIO) in men are scarce. We performed a randomized, open-label trial in men who have taken glucocorticoids (GC) for ≥3 months, and had an areal bone mineral density (aBMD) T-score ≤-1.5 standard deviations. Subjects received 20 µg/day teriparatide (n=45) or 35 mg/week risedronate (n=47) for 18 months. Primary objective was to compare lumbar spine (L1-L3) BMD measured by quantitative computed tomography (QCT). Secondary outcomes included BMD and microstructure measured by high resolution QCT (HRQCT) at the 12(th) thoracic vertebra, biomechanical effects for axial compression, anterior bending, and axial torsion evaluated by finite element (FE) analysis from HRQCT data, aBMD by dual X-ray absorptiometry, biochemical markers, and safety. Computed tomography scans were performed at 0, 6, and 18 months. A mixed model repeated measures analysis was performed to compare changes from baseline between groups. Mean age was 56.3 years. Median GC dose and duration were 8.8 mg/day and 6.4 years, respectively. 39.1% of subjects had a prevalent fracture, and 32.6% received prior bisphosphonate treatment. At 18 months, trabecular BMD had significantly increased for both treatments, with significantly greater increases with teriparatide (16.3% vs 3.8%; p=0.004). HRQCT trabecular and cortical variables significantly increased for both treatments with significantly larger improvements for teriparatide for integral and trabecular BMD and bone surface to volume ratio (BS/TV) as a microstructural measure. Vertebral strength increases at 18 months were significant in both groups (teriparatide: 26.0%-34.0%; risedronate: 4.2%-6.7%), with significantly higher increases in the teriparatide group for all loading modes (0.005 <p <0.015). Adverse events were similar between groups. None of the patients on teriparatide but 5 (10.6%) on risedronate developed new clinical fractures (p=0.056). In conclusion, in this 18-month trial in men with GIO, teriparatide showed larger improvements in spinal BMD, microstructure, and FE-derived strength than risedronate. © 2013 American Society for Bone and Mineral Research.
    Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 01/2013; · 6.04 Impact Factor
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    ABSTRACT: The first biological therapeutics in rheumatology are approaching patent expiration, encouraging development of 'follow-on' versions, known as 'biosimilars'. Biological agents range from simple replacement hormones to complex monoclonal antibodies and soluble receptors: large, intricate proteins with unique tertiary and quaternary structures that are inherently difficult to replicate. Post-translational modifications, such as glycosylation, may occur from changes in cell lines and/or manufacturing processes, resulting in products that are highly similar, but not identical, to approved 'reference' agents, hence, the term 'biosimilar', rather than 'bioidentical'. Even minor modifications in manufacturing processes, which iteratively occur with reference products due to improvements in efficiency, scale up to meet commercial demands or changes in manufacturing sites, may alter biological function and/or immunogenicity, potentially changing their safety and efficacy profile. As biosimilars are now in randomised controlled trials for treatment of rheumatic diseases, rheumatologists face decisions regarding equipoise and will need to consider their clinical use versus reference products. A clear understanding of the inherent differences between reference antibodies and biosimilars, their clinical implications and the processes governing regulation, approval and clinical use of biosimilars, is paramount. A panel of international experts in the field of rheumatology recently convened to evaluate and discuss these issues.
    Annals of the rheumatic diseases 12/2012; · 9.27 Impact Factor
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    ABSTRACT: BACKGROUND: Since approval of tocilizumab (TCZ) for treatment of rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA), interleukin 6 (IL-6) pathway inhibition was evaluated in trials of TCZ and other agents targeting the IL-6 receptor and ligand in various RA populations and other inflammatory diseases. This consensus document informs on interference with the IL-6 pathway based on evidence and expert opinion. METHODS: Preparation of this document involved international experts in RA treatment and RA patients. A systematic literature search was performed that focused on TCZ and other IL6-pathway inhibitors in RA and other diseases. Subsequently, incorporating available published evidence and expert opinion, the steering committee and a broader expert committee (both including RA patients) formulated the current consensus statement. RESULTS: The consensus statement covers use of TCZ as combination- or monotherapy in various RA populations and includes clinical, functional and structural aspects. The statement also addresses the second approved indication in Europe JIA and non-approved indications. Also early phase trials involving additional agents that target the IL-6 receptor or IL-6 were evaluated. Safety concerns, including haematological, hepatic and metabolic issues as well as infections, are addressed likewise. CONCLUSIONS: The consensus statement identifies points to consider when using TCZ, regarding indications, contraindications, screening, dose, comedication, response evaluation and safety. The document is aimed at supporting clinicians and informing patients, administrators and payers on opportunities and limitations of IL-6 pathway inhibition.
    Annals of the rheumatic diseases 11/2012; · 9.27 Impact Factor
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    ABSTRACT: Objective. To examine the frequency and phenotype of Th17 cells in the peripheral blood of patients with early non-radiographic axial SpA (early nrSpA).Methods. CD4(+) T cells were isolated from the peripheral blood of 30 early nrSpA patients, 11 AS patients and 41 age- and sex-matched healthy controls by Ficoll-Hypaque gradient and magnetic negative selection. After polyclonal stimulation, the frequency of Th17 and Th1 cells and of cells producing TNF-α or IL-10 was determined by cytometry and concentrations of IL-17, IL-22, IFN-γ, TNF-α, IL-10 and IL-4 were measured by ELISA.Results. Early nrSpA but not AS patients demonstrated a significantly lower percentage of circulating Th17, Th1 and Th17/Th1 cells, together with lower CD4-derived IL-17 and IFN-γ secretion, as compared with controls. In contrast, the percentage of circulating cells producing IL-10 or TNF-α, and the secretion of CD4-derived IL-10, TNF-α, IL-22 and IL-4 in early nrSpA were not different from controls. All Th17 cells were CD45RO(+)CD45RA(-) and CCR6(+). The frequency of circulating Th17, Th1 and Th17/Th1 was negatively correlated with BASDAI, BASFI, ASDAS-CRP, ASDAS-ESR, AS quality of life (ASQOL) and patient's global assessment in HLA-B27(+) but not in HLA-B27(-) early nrSpA patients. A positive correlation between circulating Th17 cells and BASDAI was observed in AS.Conclusion. A decreased percentage of Th17, Th1 and Th17/Th1 cells is apparent in peripheral blood CD4(+) T cells from early nrSpA. Th17, Th1 and Th17/Th1 cell numbers are related to disease activity indices in HLA-B27(+), but not in HLA-B27(-), early nrSpA patients.
    Rheumatology (Oxford, England) 10/2012; · 4.44 Impact Factor
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    ABSTRACT: OBJECTIVES: The goal of this study was to investigate the usefulness of a short ultrasound (US) assessment in gout. METHODS: Patients with gout, confirmed by urate crystal identification, and having at least one symptomatic flare in the last three months were included. Standardised US examinations of sixteen joints and eight tendons in the lower limbs were carried out. Six lesions were studied: hyperechoic spots in the synovial fluid, hyperechoic cloudy areas (HCA), bright stippled aggregates (BSA), the double contour sign (DCS), erosions and the Doppler signal. For reliability, inter-reader analyses were performed by five rheumatologists. With the results, a short US assessment was created. RESULTS: Twenty-nine consecutive patients were included (93% men). The Doppler signal, HCAs and BSAs appeared in 100%, 97% and 93% of the patients, respectively. The DCS was found in 69% of patients. The locations that were most affected were the first metatarsophalangeal joint (MTP) and the knee joints, both of which are in 93% of patients. Reliability analyses showed consistent results for erosions, the Doppler signal, HCAs and the DCS in the 1st MTP (k=0.818, k=0.958, k=0.739 and k= 0.697, respectively) and for the DCS in the knees (k=0.779). A six-minute US examination of four joints (knees and the 1st MTPs) detected HCAs or DCS in 97% of cases. CONCLUSIONS: A US examination of four joints for two elemental lesions (the DCS and HCAs) is feasible, reliable and has face and content validity as a diagnostic test in patients with crystal-proven gout.
    Clinical and experimental rheumatology 09/2012; · 2.97 Impact Factor
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    ABSTRACT: To examine the frequency and phenotype of Th17 cells in the peripheral blood of early RA (eRA) patients. CD4+ T cells were isolated from the peripheral blood of 33 eRA patients, 20 established RA patients and 53 healthy controls (HC), and from the synovial fluid of 20 established RA patients (RASF), by ficoll-hypaque gradient and magnetical negative selection. After polyclonal stimulation, the frequency of Th17 and Th1 cells was determined by flow cytometry and concentrations of IL-17, IFN-γ, TNF-α and IL-10 were measured by ELISA in cell-free supernatants. When all of our eRA patients were analyzed together, a significantly lower percentage of circulating Th17 cells and a lower CD4-derived IL-17 secretion were observed in comparison with HC. However, after stratifying by anti-CCP antibody status, circulating Th17 cells were decreased in anti-CCP(+) but not in anti-CCP(-)-eRA. All Th17 cells were CD45RO+CD45RA- and CCR6+. Dual Th17/Th1 cells were also exclusively decreased in anti-CCP(+)-eRA. Circulating Th17 and Th17/Th1 cells were negatively correlated with anti-CCP titres. When anti-CCP(+)-eRA patients were retested one year after initiating treatment with oral methotrexate, their circulating Th17 frequency was no longer different from HC. Of note, the percentage of circulating Th1 cells and the secretion of CD4-derived IFN-γ, TNF-α and IL-10 were not different between eRA patients and HC. In established RA patients, circulating Th17 and T17/Th1 cell frequencies were comparable to HC. In RASF, both Th17 and Th1 cells were increased when compared with blood of eRA patients, established RA patients and HC. Decreased circulating Th17 levels in eRA seem to be a marker of anti-CCP seropositivity, and return to levels observed in healthy controls after treatment with methotrexate.
    PLoS ONE 08/2012; 7(8):e42189. · 3.53 Impact Factor
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    ABSTRACT: The purpose of this study was to examine the role of RA Synovial Fibroblast (RASFib) IL-15 expression on B cell survival. Magnetically sorted peripheral blood memory B cells from 15 healthy subjects were cocultured with RASFib. RASFib constitutively expressed membrane IL-15. Survival of isolated B cells cultured for 6 days, below 5%, was extended in coculture with RASFib to 52+/-8% (p<0.001). IL-15 neutralizing agents but not isotype controls, reduced this rate to 31+/-6% (p<0.05). Interestingly, rhIL-15 had no effect on isolated B cells but significantly increased their survival in coculture with RASFib. In parallel, B cell IL-15R chains were upregulated in cocultures. BAFF and VCAM-1, that are expressed on RASFib, were tested as potential candidates involved in upregulating B cell IL-15R. Culture of B cells in the presence of rhBAFF or rhVCAM-1 resulted in significantly increased survival, together with upregulation of all three IL-15R chains; in parallel, rhIL-15 potentiated the anti-apoptotic effect of BAFF and VCAM-1. Both BAFF and VCAM-1 neutralizing agents downmodulated the effect of RASFib on B cell survival and IL-15R expression. In parallel, rhIL-15 had a lower effect on the survival of B cells cocultured with RASFib in the presence of BAFF or VCAM-1 neutralizing agents. Peripheral blood B cells from 15 early RA patients demonstrated an upregulated IL-15R and increased survival in cocultures. IL-15 expression on RASFib significantly contributes to the anti-apoptotic effect of RASFib on B cells. IL-15 action is facilitated by BAFF and VCAM-1 expressed on RASFib, through an upregulation of IL-15R chains.
    PLoS ONE 07/2012; 7(7):e40620. · 3.53 Impact Factor
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    ABSTRACT: Enthesitis is the hallmark of spondyloarthritis and is observed in all subtypes. Namely, a wide information on spondyloarthritis abnormalities, including synovitis, bursitis, tendinitis, enthesitis and cortical bone abnor malities (erosions and enthesophytes), can be effi - ciently perceived by ultrasound power Doppler. Furthermore, several studies on imaging of enthesis showed that imaging techniques are better than clinical examination to detect pathology at asymptomatic enthesis. Vascularized enthesitis detected by ultrasound power Doppler appears to be a valuable diagnostic tool to confirm spondyloarthritis diagnosis. This article focuses on the validity and reliability of ultrasound enthesitis assessment in the management of spondyloarthritis patients.
    Acta reumatologica portuguesa 07/2012; 37(3):217. · 0.83 Impact Factor

Publication Stats

5k Citations
665.84 Total Impact Points

Institutions

  • 1990–2014
    • Hospital Universitario La Paz
      • Servicio de Reumatología
      Madrid, Madrid, Spain
  • 2012
    • Paris Diderot University
      Lutetia Parisorum, Île-de-France, France
    • New University of Lisbon
      • Faculty of Medical Sciences
      Lisbon, Lisbon, Portugal
    • Hospital General Universitario Gregorio Marañón
      Madrid, Madrid, Spain
    • Medical University of Vienna
      Wien, Vienna, Austria
  • 2011
    • Government of Quebec
      Québec, Quebec, Canada
  • 2008–2011
    • Hospital Universitario Infanta Sofía
      Madrid, Madrid, Spain
  • 2009
    • Université René Descartes - Paris 5
      Lutetia Parisorum, Île-de-France, France
  • 1999–2009
    • Universidad Autónoma de Madrid
      Madrid, Madrid, Spain
  • 2005
    • University of Nottingham
      • Division of Academic Rheumatology
      Nottingham, ENG, United Kingdom
  • 2004
    • Royal Cornwall Hospitals NHS Trust
      Truro, England, United Kingdom
  • 2003
    • Sociedad Española de Reumatología
      Madrid, Madrid, Spain