70 results on '"Maria José Cuadrado"'
Search Results
2. Patient-reported outcome measures for systemic lupus erythematosus: an expert Delphi consensus to guide implementation in routine care
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Isabel Castrejón, Laura Cano, María José Cuadrado, Joaquín Borrás, Maria Galindo, Tarek C. Salman-Monte, Carlos Amorós, Carmen San Román, Isabel Cabezas, Marta Comellas, and Alejandro Muñoz
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Delphi ,Patient-reported outcome measures ,Quality of life ,Systemic lupus erythematosus ,Diseases of the musculoskeletal system ,RC925-935 - Abstract
Abstract Background Systemic lupus erythematosus (SLE) may result in great impact on patients’ quality of life, social relationships, and work productivity. The use of patient-reported outcome measures (PROMs) in routine care could help capture disease burden to guide SLE management and optimize disease control. We aimed to explore the current situation, appropriateness, and feasibility of PROMs to monitor patients with SLE in routine care, from healthcare professionals’ and patients’ perspectives. Methods A scientific committee developed a Delphi questionnaire, based on a focus group with patients and a literature review, including 22 statements concerning: 1) Use of PROMs in routine care (n = 2); 2) PROMs in SLE management (n = 13); 3) Multidisciplinary management of patients with SLE (n = 4), and 4) Aspects on patient empowerment (n = 3). Statements included in Sects. 2–4 were assessed from three perspectives: current use, appropriateness, and feasibility (with currently available resources). For each statement, panellists specified their level of agreement using a 7-point Likert scale. A consensus was reached when ≥ 70% of the panellists agreed (6,7) or disagreed (1,2) on each statement. Results Fifty-nine healthcare professionals and 16 patients with SLE participated in the Delphi-rounds. A consensus was reached on the value of PROMs to improve SLE management (83%) and the key role of healthcare professionals (77%) and the need for a digital tool connected to the electronic medical record (85%) to promote and facilitate PROMs collection. PROMs most frequently used in clinical practice are pain (56%), patient’s global assessment (44%) and fatigue (39%), all on visual analogue scales. Panellists agreed on the need to implement multidisciplinary consultation (79%), unify complementary tests (88%), incorporate pharmacists into the healthcare team (70%), and develop home medication dispensing and informed telepharmacy programmes (72%) to improve quality of care in patients with SLE. According to panellists, patient associations (82%) and nurses (80%) are critical to educate and train patients on PROMs to enhance patient empowerment. Conclusions Although pain, fatigue, and global assessment were identified as the most feasible, PROMs are not widely used in routine care in Spain. The present Delphi consensus can provide a road map for their implementation being key for SLE management.
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- 2024
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3. 16th International Congress on Antiphospholipid Antibodies Task Force Report on Antiphospholipid Syndrome Treatment Trends
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Thomas L. Ortel, Hannah Cohen, Maria G Tektonidou, Doruk Erkan, Anisur Rahman, David J. Williams, Jason S. Knight, David A. Isenberg, Rohan Willis, Alí Duarte-García, Maria José Cuadrado, Jane E. Salmon, Scott C. Woller, and Danieli Andrade
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medicine.medical_specialty ,030204 cardiovascular system & hematology ,Thrombophilia ,direct oral anticoagulants ,03 medical and health sciences ,0302 clinical medicine ,Rheumatology ,Antiphospholipid syndrome ,complement inhibition ,Vitamin D and neurology ,Medicine ,Humans ,biologics ,Intensive care medicine ,030203 arthritis & rheumatology ,anti-β2-glycoprotein I peptides ,business.industry ,potential new players ,Anticoagulants ,Hydroxychloroquine ,Thrombosis ,Congresses as Topic ,medicine.disease ,Antiphospholipid Syndrome ,Belimumab ,Clinical research ,Papers ,Factor Xa ,Antibodies, Antiphospholipid ,Rituximab ,business ,medicine.drug - Abstract
Antiphospholipid syndrome (APS), an acquired autoimmune thrombophilia, is characterised by thrombosis and/or pregnancy morbidity in association with persistent antiphospholipid antibodies. The 16th International Congress on Antiphospholipid Antibodies Task Force on APS Treatment Trends reviewed the current status with regard to existing and novel treatment trends for APS, which is the focus of this Task Force report. The report addresses current treatments and developments since the last report, on the use of direct oral anticoagulants in patients with APS, antiplatelet agents, adjunctive therapies (hydroxychloroquine, statins and vitamin D), targeted treatment including rituximab, belimumab, and anti-TNF agents, complement inhibition and drugs based on peptides of beta-2-glycoprotein I. In addition, the report summarises potential new players, including coenzyme Q10, adenosine receptor agonists and adenosine potentiation. In each case, the report provides recommendations for clinicians, based on the current state of the art, and suggests a clinical research agenda. The initiation and development of appropriate clinical studies requires a focus on devising suitable outcome measures, including a disease activity index, an optimal damage index, and a specific quality of life index.
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- 2020
4. Pregnancy success rate and response to heparins and/or aspirin differ in women with antiphospholipid antibodies according to their Global AntiphosPholipid Syndrome Score
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Dario Roccatello, Karen Schreiber, Maria José Cuadrado, Elena Rubini, Massimo Radin, Irene Cecchi, and Savino Sciascia
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Adult ,medicine.medical_specialty ,Standard of care ,medicine.drug_class ,Low molecular weight heparin ,03 medical and health sciences ,0302 clinical medicine ,Risk groups ,Fibrinolytic Agents ,Rheumatology ,Pregnancy ,Antiphospholipid syndrome ,medicine ,Humans ,030212 general & internal medicine ,Retrospective Studies ,030203 arthritis & rheumatology ,Aspirin ,biology ,business.industry ,Obstetrics ,Heparin, Low-Molecular-Weight ,Antiphospholipid Syndrome ,medicine.disease ,Pregnancy Complications ,Anesthesiology and Pain Medicine ,Antibodies, Antiphospholipid ,biology.protein ,Female ,Antibody ,business ,Live birth ,Live Birth ,medicine.drug - Abstract
The current treatment to prevent pregnancy morbidity (PM) associated with antiphospholipid antibodies (aPL) is based on the use of low dose aspirin and low molecular weight heparin (henceforth defined as standard of care (SoC) treatment). Despite the SoC, up to 30% of women with aPL continue to have pregnancy complications. The global antiphospholipid syndrome (APS) score (GAPSS) is a tool to quantify the risk for the aPL-related clinical manifestations. In this study, we investigated the individual clinical response to SoC in women with aPL after stratifying them according to their GAPSS.One-hundred-fourty-three women (352 pregnancies) with aPL ever pregnant treated with SoC therapy were included. The patients GAPSS was then grouped according to the patients' GAPSS into low risk (6), medium risk (6-11), and high risk (≥12).The live birth rate was 70.5% (248 out of the 352 pregnancies), 45 patients (31%) experienced at least one event of PM, defined as early or late. Patients were stratified according to GAPSS values, in order to identify a low risk group (GAPSS6, n = 72), a medium risk group (GAPSS 6-11, n = 66) and a high risk group (GAPSS ≥12, n = 5). When considering patients who ever experienced any PM while treated with SoC, all patients in the high risk group experienced PM, while patients in the medium group had a significant higher rate of PM when compared to the low risk group [29 (43.9%) patients V.s. 11 (15.3%), respectively; p0.001]. When analysing the number of pregnancies in the three groups, patients in the high risk group had significantly lower live birth rates, when compared to the other groups [11 (40.7%) live births vs. 100 (62.1%) and 137 (82.5%), respectively; p0.05]. Furthermore, patients with medium risk group also had significantly lower live birth rates, when compared to the lower risk group (p0.001).GAPSS might be a valuable tool for to identify patients with a higher likelihood of response to SoC.
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- 2020
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5. Correction: Patient-reported outcome measures for systemic lupus erythematosus: an expert Delphi consensus to guide implementation in routine care
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Isabel Castrejón, Laura Cano, María José Cuadrado, Joaquín Borrás, Maria Galindo, Tarek C. Salman-Monte, Carlos Amorós, Carmen San Román, Isabel Cabezas, Marta Comellas, and Alejandro Muñoz
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Diseases of the musculoskeletal system ,RC925-935 - Published
- 2024
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6. Thrombotic microangiopathy in untreated myeloma patients receiving carfilzomib, cyclophosphamide and dexamethasone on the CARDAMON study
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Richard G. Jenner, Roger G. Owen, Lydia Eccersley, Laura Clifton-Hadley, Rakesh Popat, William R. Wilson, Elizabeth H Phillips, Selina J Chavda, Kwee Yong, Marie Scully, Michael Sheaff, Matthew Streetly, Gavin Pang, Karthik Ramasamy, Ceri Bygrave, Andres Virchis, James D. Cavenagh, Jonathan Sive, Gordon Cook, Sumaiya Kamora, Marquita Camilleri, Maria José Cuadrado, Michael A Chapman, and Reuben Benjamin
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Male ,medicine.medical_specialty ,Thrombotic microangiopathy ,Cyclophosphamide ,thrombocytopenia ,Gastroenterology ,Dexamethasone ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Refractory ,Internal medicine ,hemic and lymphatic diseases ,Antineoplastic Combined Chemotherapy Protocols ,Medicine ,Humans ,Dosing ,thrombotic haemolytic anaemias ,Aged ,clinical trials ,carfilzomib ,Manchester Cancer Research Centre ,business.industry ,Thrombotic Microangiopathies ,ResearchInstitutes_Networks_Beacons/mcrc ,Acute kidney injury ,Hematology ,Acute Kidney Injury ,Middle Aged ,medicine.disease ,Carfilzomib ,myeloma ,chemistry ,030220 oncology & carcinogenesis ,Premedication ,Female ,business ,Multiple Myeloma ,Oligopeptides ,030215 immunology ,medicine.drug - Abstract
Proteasome inhibitors have been associated with thrombotic microangiopathy (TMA) - a group of disorders characterised by occlusive microvascular thrombosis causing microangiopathic haemolytic anaemia, thrombocytopenia and end-organ damage. To date, carfilzomib-associated TMA has predominantly been described in relapsed/refractory myeloma patients. We report eight patients with newly diagnosed myeloma who experienced TMA events while receiving carfilzomib on the phase II CARDAMON trial. The first three occurred during maintenance single-agent carfilzomib, two occurred at induction with carfilzomib given with cyclophosphamide and dexamethasone (KCd) and three occurred during KCd consolidation. At TMA presentation 6/8 were hypertensive; 7/8 had acute kidney injury and in three, renal impairment persisted after resolution of TMA in other respects. The mechanism of carfilzomib-associated TMA remains unclear, though patients with known hypertension seem particularly susceptible. Given the first three cases occurred during maintenance after a longer than five-week treatment break, a protocol amendment was instituted with: aggressive hypertension management, carfilzomib step-up dosing (20 mg/m2 on day 1) at start of maintenance before dose escalation to 56 mg/m2 maximum, and adding 10 mg dexamethasone as premedication to maintenance carfilzomib infusions. No further TMA events occurred during maintenance following this amendment and the TMA incidence reduced from 4·2 to 1·6 per 1 000 patient cycles.
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- 2020
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7. Hydroxychloroquine in patients with rheumatic diseases during the COVID-19 pandemic: a letter to clinicians
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Evelyne Vinet, Savino Sciascia, Karen Schreiber, Caroline Gordon, Anne Voss, Jane E. Salmon, Dario Roccatello, Hannah Cohen, Marta Mosca, Sue Pavord, David A. Isenberg, Saskia Middeldorp, Linda Watkins, Massimo Radin, Ian Giles, Søren Jacobsen, Ian N. Bruce, Maria José Cuadrado, Beverley J. Hunt, Vascular Medicine, ACS - Pulmonary hypertension & thrombosis, and Amsterdam Reproduction & Development (AR&D)
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2019-20 coronavirus outbreak ,medicine.medical_specialty ,Coronavirus disease 2019 (COVID-19) ,business.industry ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Immunology ,MEDLINE ,Hydroxychloroquine ,Rheumatology ,Correspondence ,Pandemic ,Immunology and Allergy ,Medicine ,In patient ,business ,Intensive care medicine ,medicine.drug - Published
- 2020
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8. Anticoagulation in patients with concomitant lupus nephritis and thrombotic microangiopathy: a multicentre cohort study
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Ishita Aggarwal, Maria José Cuadrado, Massimo Radin, Maria Dall'Era, Mauro Papotti, Dario Roccatello, Jinoos Yazdany, Karen Schreiber, Antonella Barreca, Savino Sciascia, and Roberta Fenoglio
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Genetics and Molecular Biology (all) ,0301 basic medicine ,medicine.medical_specialty ,Thrombotic microangiopathy ,Immunology ,Population ,SLE ,Lupus nephritis ,anticardiolipin antibodies ,Biochemistry ,Article ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,0302 clinical medicine ,systemic lupus erythematosus ,Rheumatology ,Antiphospholipid syndrome ,Internal medicine ,Immunology and Allergy ,Medicine ,TMA ,education ,lupus nephritis ,030203 arthritis & rheumatology ,education.field_of_study ,business.industry ,antiphospholipid antibodies ,Retrospective cohort study ,medicine.disease ,thrombotic microangiopathy ,030104 developmental biology ,antiphospholipid syndrome ,Biochemistry, Genetics and Molecular Biology (all) ,Concomitant ,business ,Kidney disease ,Cohort study - Abstract
The management of lupus nephritis (LN) and concomitant thrombotic microangiopathy (TMA), with or without antiphospholipid antibodies (aPL), remains controversial, and few studies are available to inform clinical management.1–4 The purpose of this multicentre retrospective study was to analyse the impact of anticoagulation (vitamin K antagonists (VKAs) and/or heparins) in addition to conventional immunosuppression on kidney outcomes (assessed at 12 months, according to the Kidney Disease: Improving Global Outcomes-KDIGOguidelines5) in patients with biopsy-proven LN and concomitant TMA. Data source, population and statistical analysis are detailed in the online supplementary material 1. Anticoagulation was considered if given for at least three consecutive months after TMA diagnosis.### Supplementary data [annrheumdis-2018-214559supp002.docx] We retrospectively identified 97 patients with biopsy-proven LN and TMA (2007–2017). See online supplementary table 1 for clinical and demographic characteristics. Laboratory parameters were collected at the time of the biopsy. The mean age of patients was 38.9±15.2 years (13–69) and 85 females (87.6%). Most had proliferative LN (class …
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- 2018
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9. Can we treat systemic lupus erythematosus and other autoimmune diseases without oral steroids?
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Maria José Cuadrado, Eugenia Enríquez Merayo, Savino Sciascia, and Dario Roccatello
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musculoskeletal diseases ,0301 basic medicine ,medicine.medical_specialty ,medicine.medical_treatment ,Immunology ,Osteoporosis ,macromolecular substances ,biologic ,chronic damage ,Glucocorticoid ,immunosuppression ,infection ,osteoporosis ,side effects ,sparing agents ,systemic lupus erythematosus ,Immunology and Allergy ,Autoimmune Diseases ,03 medical and health sciences ,0302 clinical medicine ,immune system diseases ,Humans ,Lupus Erythematosus, Systemic ,Medicine ,skin and connective tissue diseases ,Glucocorticoids ,Randomized Controlled Trials as Topic ,030203 arthritis & rheumatology ,Biological Products ,business.industry ,Immunosuppression ,medicine.disease ,Dermatology ,030104 developmental biology ,Rituximab ,business ,Immunosuppressive Agents ,hormones, hormone substitutes, and hormone antagonists ,medicine.drug - Abstract
Glucocorticoids (GCs) have traditionally been the center of systemic lupus erythematosus (SLE) treatment and they continue to be recommended by the EULAR and ACR as the first-line therapy for sever...
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- 2018
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10. Is air pollution affecting the disease activity in patients with systemic lupus erythematosus? State of the art and a systematic literature review
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Dario Padovan, Maria José Cuadrado, Savino Sciascia, Dario Roccatello, Stefano Massaglia, Massimo Radin, Enrico Heffler, Cristiana Peano, and Gregory Winston Gilcrease
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lcsh:Immunologic diseases. Allergy ,medicine.medical_specialty ,Air pollution ,MEDLINE ,Autoimmunity ,Environment ,medicine.disease_cause ,Subspecialty ,Disease activity ,Systemic lupus erythematosus ,systemic lupus erythematosus ,Internal medicine ,Environmental health ,medicine ,Literature Review ,autoimmunity ,environment ,business.industry ,medicine.disease ,Rheumatology ,Systematic review ,Observational study ,business ,lcsh:RC581-607 ,Rheumatism - Abstract
Objective: It has been documented that several major components of air pollution, including trace elements and polycyclic aromatic hydrocarbons, are associated with the prevalence of systemic lupus erythematosus (SLE). However, the impact of air pollution on the SLE disease activity is still elusive. In this paper, we review the current evidence investigating the link between air pollution, especially when measured as PM2.5, and SLE severity and activity. Methods: A detailed literature search was applied a priori to the Ovid MEDLINE In-Process and Other Non-Indexed Citation 1986 to present. Presented abstracts from the European League Against Rheumatism and American College of Rheumatology (ACR)/Association for Rheumatology Health Professionals (ARHP) Annual Meetings (2011-2018) were also screened. Results: Out of a total of 1354 papers retrieved from search and references list for detailed evaluation, data from 652 patients with SLE from three studies were analyzed. Two studies had an observational longitudinal design, counting for 348 patients with a follow-up of 24 months and 79 months. Retrieved studies differed for disease activity assessment and air pollution quantifications. Conclusion: Current evidence suggests that variations in air pollution may influence the disease activity in patients with SLE. However, the sample size, methodological biases, and differences across the studies make further research mandatory. Understanding the increased burden of SLE and its complications, not only from a medical, but also from a socio-demographic perspective, including an exposure to pollutants, should have implications for resource allocation and access to subspecialty care.
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- 2019
11. Prevalence of Antiphospholipid Antibodies Negativisation in Patients with Antiphospholipid Syndrome: A Long-Term Follow-Up Multicentre Study
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Massimo Radin, Irene Cecchi, Maria Angeles Aguirre Zamorano, Karen Schreiber, Dario Roccatello, Maria José Cuadrado, and Savino Sciascia
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Adult ,Male ,0301 basic medicine ,Pediatrics ,medicine.medical_specialty ,Long term follow up ,Observation period ,030204 cardiovascular system & hematology ,Severity of Illness Index ,03 medical and health sciences ,0302 clinical medicine ,Pregnancy ,immune system diseases ,Antiphospholipid syndrome ,Humans ,Medicine ,In patient ,Aps diagnosis ,neoplasms ,Aged ,Retrospective Studies ,biology ,business.industry ,Anticoagulants ,Thrombosis ,Hematology ,Middle Aged ,Antiphospholipid Syndrome ,medicine.disease ,030104 developmental biology ,Lupus Coagulation Inhibitor ,Cohort ,Antibodies, Antiphospholipid ,biology.protein ,Female ,Antibody ,business ,Follow-Up Studies - Abstract
Objective This article aims to analyse the rate of antiphospholipid antibodies (aPL) negativisation in patients with antiphospholipid syndrome (APS), and to evaluate potential new clinical manifestations after negativisation and/or aPL fluctuations in a long-term follow-up. Methods Inclusion criteria are (1) any patients with an APS diagnosis according to the current Sydney criteria and (2) patients in whom aPL negativisation occurred. aPL negativisation was defined as repeated aPL measurements on at least two consecutive occasions at least 12 weeks apart, with a follow-up of at least 1 year since aPL first turned negative. Results Out of 259 APS patients, a total of 23 patients (8.9%) met the inclusion criteria for persistent aPL negativisation. Patients were followed-up for 14.4 ± 8.1 years, experienced aPL negativisation after a mean of 5.3 ± 3.5 years and were followed-up after experiencing the aPL negativisation for a mean of 7.6 ± 5.8 years. Seventeen patients (73.9%) presented with thrombotic APS, 2 with pregnancy morbidity (8.7%) and 4 (17.4%) with both. Most of the patients (18; 78.3%) had a single aPL positivity, 5 (21.7%) double, while no triple aPL positivity was observed. At the time of data collection, after aPL negativisation, anticoagulation was stopped in 8 patients with previous thrombotic venous event (8/21, 38%) according to the treating physicians' judgements. None of the patients experienced any recurrent thrombotic event during the follow-up period after their aPL negativisation. Conclusion In our patient cohort consisting of 259 patients with definitive APS, we observed over a mean observation period of > 5 years, that aPL negativisation occurred in approximately 9% of patients. Negativisation occurred most often in patients who were previously found to be positive for only one aPL.
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- 2019
12. EULAR recommendations for the management of antiphospholipid syndrome in adults
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Angela Tincani, Elisabet Svenungsson, Raquel Ferrer-Oliveras, Luigi Raio, Nathalie Costedoat-Chalumeau, Marta Mosca, Judith King, Pier Luigi Meroni, Laura Andreoli, Francesca Marchiori, Karen Hambly, Vittorio Pengo, Maria G Tektonidou, Marteen Limper, Ljudmila Stojanovich, Zahir Amoura, Michael M. Ward, Ricard Cervera, Munther A. Khamashta, Denis Wahl, Guillermo Ruiz-Irastorza, Yehuda Shoenfeld, Maria José Cuadrado, and Thomas Dörner
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Adult ,Male ,medicine.medical_specialty ,medicine.drug_class ,Immunology ,Low molecular weight heparin ,antiphospholipid antibodies ,antiphospholipid syndrome ,management ,pregnancy morbidity ,recommendations ,systemic lupus erythematosus ,thrombosis ,Antibodies, Antiphospholipid ,Anticoagulants ,Female ,Humans ,Pregnancy ,Pregnancy Complications ,Rheumatology ,Risk Factors ,Venous Thrombosis ,Antiphospholipid Syndrome ,Practice Guidelines as Topic ,Antiphospholipid ,030204 cardiovascular system & hematology ,General Biochemistry, Genetics and Molecular Biology ,Antibodies ,03 medical and health sciences ,0302 clinical medicine ,RZ ,Antiphospholipid syndrome ,Internal medicine ,medicine ,Immunology and Allergy ,RM695 ,610 Medicine & health ,030203 arthritis & rheumatology ,Aspirin ,Rivaroxaban ,business.industry ,Hydroxychloroquine ,medicine.disease ,Thrombosis ,Venous thrombosis ,business ,medicine.drug - Abstract
The objective was to develop evidence-based recommendations for the management of antiphospholipid syndrome (APS) in adults. Based on evidence from a systematic literature review and expert opinion, overarching principles and recommendations were formulated and voted. High-risk antiphospholipid antibody (aPL) profile is associated with greater risk for thrombotic and obstetric APS. Risk modification includes screening for and management of cardiovascular and venous thrombosis risk factors, patient education about treatment adherence, and lifestyle counselling. Low-dose aspirin (LDA) is recommended for asymptomatic aPL carriers, patients with systemic lupus erythematosus without prior thrombotic or obstetric APS, and non-pregnant women with a history of obstetric APS only, all with high-risk aPL profiles. Patients with APS and first unprovoked venous thrombosis should receive long-term treatment with vitamin K antagonists (VKA) with a target international normalised ratio (INR) of 2–3. In patients with APS with first arterial thrombosis, treatment with VKA with INR 2–3 or INR 3–4 is recommended, considering the individual’s bleeding/thrombosis risk. Rivaroxaban should not be used in patients with APS with triple aPL positivity. For patients with recurrent arterial or venous thrombosis despite adequate treatment, addition of LDA, increase of INR target to 3–4 or switch to low molecular weight heparin may be considered. In women with prior obstetric APS, combination treatment with LDA and prophylactic dosage heparin during pregnancy is recommended. In patients with recurrent pregnancy complications, increase of heparin to therapeutic dose, addition of hydroxychloroquine or addition of low-dose prednisolone in the first trimester may be considered. These recommendations aim to guide treatment in adults with APS. High-quality evidence is limited, indicating a need for more research.
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- 2019
13. Pregnancy outcomes in mixed connective tissue disease: a multicentre study
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Laura Andreoli, Chiara Benedetto, Jill P. Buyon, Dario Roccatello, Munther A. Khamashta, Luca Marozio, Teresa Caleiro, Danieli Andrade, Franco Franceschini, Maria Angeles Aguirre, Massimo Radin, Irene Cecchi, Karen Schreiber, Savino Sciascia, Elena Gibbone, Maria José Cuadrado, and Peter M. Izmirly
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Gestational hypertension ,Adult ,medicine.medical_specialty ,Intrauterine growth restriction ,autoimmune disease ,030204 cardiovascular system & hematology ,anti-U1RNP ,Ribonucleoprotein, U1 Small Nuclear ,03 medical and health sciences ,0302 clinical medicine ,Rheumatology ,Pregnancy ,medicine ,antibodies ,Humans ,Lupus Erythematosus, Systemic ,Pharmacology (medical) ,Autoantibodies ,Mixed Connective Tissue Disease ,Retrospective Studies ,030203 arthritis & rheumatology ,Eclampsia ,Fetal Growth Retardation ,congenital heart block ,Obstetrics ,business.industry ,pregnancy complications ,mixed connective tissue disease ,neonatal lupus ,pregnancy ,Infant, Newborn ,Pregnancy Outcome ,Retrospective cohort study ,Hypertension, Pregnancy-Induced ,Stillbirth ,medicine.disease ,Gestational diabetes ,Pregnancy Complications ,Abortion, Spontaneous ,Diabetes, Gestational ,Heart Block ,Cohort ,Female ,Live birth ,business ,Live Birth - Abstract
Objectives In this study we aimed to investigate foetal and maternal pregnancy outcomes from a large multicentre cohort of women diagnosed with MCTD and anti-U1RNP antibodies. Methods This multicentre retrospective cohort study describes the outcomes of 203 pregnancies in 94 consecutive women ever pregnant who fulfilled the established criteria for MCTD with confirmed U1RNP positivity. Results The foetal outcomes in 203 pregnancies were as follows: 146 (71.9%) live births, 38 (18.7%) miscarriages (first trimester pregnancy loss of Conclusion In our multicentre cohort, women with MCTD had a live birth rate of 72%. While the true frequency of heart block associated with anti-U1RNP remains to be determined, this study might raise the consideration of echocardiographic surveillance in this setting. Pregnancy counselling should be considered in women with MCTD.
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- 2019
14. Infliximab Biosimilars in the Treatment of Inflammatory Bowel Diseases: A Systematic Review
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Maria José Cuadrado, Dario Roccatello, Massimo Radin, and Savino Sciascia
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medicine.medical_specialty ,Animals ,Antibodies, Monoclonal ,Biosimilar Pharmaceuticals ,Humans ,Inflammatory Bowel Diseases ,Infliximab ,Retrospective Studies ,Treatment Outcome ,Biotechnology ,Pharmacology ,Pharmacology (medical) ,Medical care ,Antibodies ,03 medical and health sciences ,0302 clinical medicine ,Pharmacotherapy ,Monoclonal ,medicine ,Intensive care medicine ,Biological therapies ,business.industry ,Retrospective cohort study ,Biosimilar ,General Medicine ,030220 oncology & carcinogenesis ,Immunology ,030211 gastroenterology & hepatology ,business ,medicine.drug - Abstract
Biological therapies represent a fundamental innovation for the management of inflammatory bowel diseases (IBD). However, many biological originators have reached, or are about to reach, patent expiry and long-term therapy costs have become progressively unsustainable. CT-P13, a biosimilar of the anti-tumor necrosis factor (anti-TNF) monoclonal antibody infliximab, might represent a significant alternative to its originator, with the potential to decrease medical care costs and, therefore, become available to a large number of patients.In this systematic review, we analyzed the data from available clinical trials that recently investigated the validity of indication extrapolation of CT-P13 for the treatment of IBD in naïve patients and in patients who switched from its originator infliximab, focusing on clinical efficacy, safety and immunogenicity.A detailed literature search was developed a priori to identify articles that investigated the validity of indication extrapolation of CT-P13 for the treatment of IBD in TNF inhibitor treatment-naïve patients and in patients who switched from the originator infliximab. This was applied to Ovid MEDLINE, In-Process and Other Non-Indexed Citations, EMBASE, Cochrane Central Register of Controlled Trials, and Scopus for content from 2012 to September 2016.We based our review on the available data from 11 studies that included a total of 1007 IBD patients: 570 patients suffering from Crohn's disease (294 switched and 276 naïve), 435 patients suffering from ulcerative colitis (127 switched and 308 naïve), and two IBD unclassified patients (switched). Overall, no significant difference in efficacy and safety between the originator infliximab and its biosimilar CT-P13 was observed. When assessing the safety of CT-P13, we found that 9.2% of patients experienced adverse effects (4.1% infusion-related reactions and 4.3% infections).The analyzed studies did not report a significant difference in terms of efficacy, safety and immunogenicity when comparing the clinical experience with CT-P13 with the available literature data on the originator treatment in IBD. However, some debate is ongoing regarding interchangeability and immunogenicity.
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- 2016
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15. Non-vitamin K antagonist oral anticoagulants and antiphospholipid syndrome
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Dario Roccatello, Savino Sciascia, Chary López-Pedrera, Irene Cecchi, Maria José Cuadrado, and Clara Pecoraro
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medicine.medical_specialty ,Vitamin K ,medicine.drug_class ,anti-phospholipid antibodies ,apixaban ,Administration, Oral ,Hemorrhage ,030204 cardiovascular system & hematology ,Pharmacology ,Antithrombins ,Dabigatran ,Food-Drug Interactions ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Rheumatology ,Pregnancy ,Edoxaban ,anti-phospholipid syndrome ,dabigatran ,rivaroxaban ,thrombosis ,medicine ,Humans ,Pharmacology (medical) ,030212 general & internal medicine ,Intensive care medicine ,Rivaroxaban ,business.industry ,Liver Diseases ,Anticoagulant ,Warfarin ,Anticoagulants ,Thrombosis ,Vitamin K antagonist ,Antiphospholipid Syndrome ,Pregnancy Complications ,Breast Feeding ,chemistry ,Direct thrombin inhibitor ,Lupus Coagulation Inhibitor ,Female ,Kidney Diseases ,Apixaban ,business ,Factor Xa Inhibitors ,medicine.drug - Abstract
The current treatment of thrombotic APS patients includes long-term anticoagulation with oral vitamin K antagonists (VKAs), with warfarin being the one most commonly used. However, the use of VKAs can be challenging, especially in patients with APS. VKAs monitoring in patients with aPL is complicated by the heterogeneous responsiveness to LAs of reagents used in the International Normalized Ratio test, potentially resulting in instability of anticoagulation. For decades, VKAs were the only available oral anticoagulants. However, non-VKA oral anticoagulants, including a direct thrombin inhibitor (dabigatran etexilate) and direct anti-Xa inhibitors (rivaroxaban, apixaban and edoxaban), are currently available. The use of these agents may represent a major step forward since, unlike VKAs, they have few reported drug interactions and they do not interact with food or alcohol intake, thereby resulting in more stable anticoagulant intensity. Most importantly, monitoring their anticoagulant intensity is not routinely required due to their predictable anticoagulant effects. In this review, we discuss the clinical and laboratory aspects of non-VKA oral anticoagulants, focusing on the available evidence regarding their use in patients with APS.
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- 2016
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16. Catastrophic antiphospholipid syndrome on switching from warfarin to rivaroxaban
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Maria José Cuadrado, Maeve P. Crowley, and Beverley J. Hunt
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030203 arthritis & rheumatology ,Rivaroxaban ,medicine.medical_specialty ,business.industry ,Warfarin ,Hematology ,030204 cardiovascular system & hematology ,Catastrophic antiphospholipid syndrome ,03 medical and health sciences ,0302 clinical medicine ,Medicine ,business ,Intensive care medicine ,medicine.drug - Published
- 2017
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17. Circulating microRNAs as biomarkers of disease and typification of the atherothrombotic status in antiphospholipid syndrome
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Chary López-Pedrera, María Teresa Herranz, Francisco Velasco, Rocío González-Conejero, Yolanda Jimenez-Gomez, Massimo Radin, Patricia Ruiz-Limon, Irene Cecchi, Maria José Cuadrado, Maria del Carmen Abalos-Aguilera, Carlos Perez-Sanchez, Constantino Martínez, Jesús Lozano-Herrero, P. Segui, Savino Sciascia, María Julia Hernandez-Vidal, Nuria Barbarroja, Eduardo Collantes-Estevez, María Luque-Tévar, Maria Angeles Aguirre, and Iván Arias de la Rosa
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0301 basic medicine ,Adult ,Male ,Disease ,medicine.disease_cause ,Article ,Autoimmunity ,Cohort Studies ,03 medical and health sciences ,Young Adult ,Antiphospholipid syndrome ,medicine ,Humans ,Circulating MicroRNA ,Aged ,Autoimmune disease ,Neoplastic ,biology ,business.industry ,Case-control study ,Coagulation & its Disorders ,Thrombosis ,Hematology ,Middle Aged ,medicine.disease ,Antiphospholipid Syndrome ,Atherosclerosis ,Prognosis ,Gene Expression Regulation, Neoplastic ,030104 developmental biology ,Gene Expression Regulation ,Case-Control Studies ,Immunology ,biology.protein ,Female ,Sample collection ,Antibody ,business ,Biomarkers ,Follow-Up Studies - Abstract
We aimed to identify the plasma miRNA profile of antiphospholipid syndrome (APS) patients and to investigate the potential role of specific circulating miRNAs as non-invasive disease biomarkers. Ninety APS patients and 42 healthy donors were recruited. Profiling of miRNAs by PCR-array in plasma of APS patients identified a set of miRNAs differentially expressed and collectively involved in clinical features. Logistic regression and ROC analysis identified a signature of 10 miRNA ratios as biomarkers of disease. In addition, miRNA signature was related to fetal loss, atherosclerosis, and type of thrombosis, and correlated with parameters linked to inflammation, thrombosis, and autoimmunity. Hard clustering analysis differentiated 3 clusters representing different thrombotic risk profile groups. Significant differences between groups for several miRNA ratios were found. Moreover, miRNA signature remained stable over time, demonstrated by their analysis three months after the first sample collection. Parallel analysis in two additional cohorts of patients, including thrombosis without autoimmune disease, and systemic lupus erythematosus without antiphospholipid antibodies, each displayed specific miRNA profiles that were distinct from those of APS patients. In vitro, antiphospholipid antibodies of IgG isotype promoted deregulation in selected miRNAs and their potential atherothrombotic protein targets in monocytes and endothelial cells. Taken together, differentially expressed circulating miRNAs in APS patients, modulated at least partially by antiphospholipid antibodies of IgG isotype, might have the potential to serve as novel biomarkers of disease features and to typify patients' atherothrombotic status, thus constituting a useful tool in the management of the disease.
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- 2018
18. Effect of Additional Treatments Combined with Conventional Therapies in Pregnant Patients with High-Risk Antiphospholipid Syndrome: A Multicentre Study
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Maria Gerosa, Jaume Alijotas-Reig, Marta Tonello, Véronique Ramoni, Pier L. Meroni, Maria Tiziana Bertero, Michal J. Simchen, Ewa Haladyj, Karoline Mayer-Pickel, Savino Sciascia, Luca Marozio, José Omar Latino, Elvira Grandone, Angela Tincani, Sara Tenti, Arsène Mekinian, Ariela Hoxha, N. Costedoat-Chalumeau, Maria José Cuadrado, Sebastián Udry, Amelia Ruffatti, Sara De Carolis, Munther A. Khamashta, Nathalie Morel, Vittorio Pengo, Tatiana Reshetnyak, Laura Andreoli, Fátima Serrano, and Aldo Maina
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Administration, Oral ,Anticardiolipin ,Antiphospholipid ,030204 cardiovascular system & hematology ,0302 clinical medicine ,Pregnancy ,Prednisone ,plasma exchange ,Birth Rate ,Lupus anticoagulant ,Plasma Exchange ,Pregnancy Outcome ,Immunoglobulins, Intravenous ,Hematology ,Antiphospholipid Syndrome ,Combined Modality Therapy ,Thrombosis ,Lupus Coagulation Inhibitor ,Administration ,Antibodies, Antiphospholipid ,Female ,Steroids ,Intravenous ,Live birth ,Live Birth ,Hydroxychloroquine ,medicine.drug ,Oral ,Adult ,Risk ,medicine.medical_specialty ,hydroxychloroquine ,Immunoglobulins ,intravenous immunoglobulins ,Antibodies ,03 medical and health sciences ,Antiphospholipid syndrome ,Internal medicine ,medicine ,Humans ,antiphospholipid syndrome ,low-dose steroids ,Retrospective Studies ,030203 arthritis & rheumatology ,business.industry ,Retrospective cohort study ,medicine.disease ,MAC GIN ,Antibodies, Anticardiolipin ,Pregnancy Complications ,Settore MED/40 - GINECOLOGIA E OSTETRICIA ,business - Abstract
The effect of additional treatments combined with conventional therapy on pregnancy outcomes was examined in high-risk primary antiphospholipid syndrome (PAPS) patients to identify the most effective treatment strategy. The study's inclusion criteria were (1) positivity to lupus anticoagulant alone or associated with anticardiolipin and/or anti-β2 glycoprotein I antibodies; (2) a history of severe maternal–foetal complications (Group I) or a history of one or more pregnancies refractory to conventional therapy leading to unexplained foetal deaths not associated with severe maternal–foetal complications (Group II). Two different additional treatments were considered: oral—low-dose steroids (10–20 mg prednisone daily) and/or 200 to 400 mg daily doses of hydroxychloroquine and parenteral—intravenous immunoglobulins at 2 g/kg per month and/or plasma exchange. The study's primary outcomes were live birth rates and pregnancy complications. A total of 194 pregnant PAPS patients attending 20 tertiary centres were retrospectively enrolled. Hydroxychloroquine was found to be linked to a significantly higher live birth rate with respect to the other oral treatments in the Group II patients. The high (400 mg) versus low (200 mg) doses of hydroxychloroquine (p = 0.036) and its administration before versus during pregnancy (p = 0.021) were associated with a significantly higher live birth rate. Hydroxychloroquine therapy appeared particularly efficacious in the PAPS patients without previous thrombosis. Parenteral treatments were associated with a significantly higher live birth rate with respect to the oral ones (p = 0.037), particularly in the Group I patients. In conclusion, some additional treatments were found to be safe and efficacious in high-risk PAPS pregnant women.
- Published
- 2018
19. Upcoming biological therapies in systemic lupus erythematosus
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Savino Sciascia, Dario Roccatello, Simone Baldovino, Maria José Cuadrado, Eva Talavera-Garcia, and Elisa Mengatti
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medicine.medical_specialty ,Immunology ,Disease ,Pathogenesis ,Biological agents ,Therapeutic approach ,Systemic lupus erythematosus ,immune system diseases ,medicine ,Animals ,Humans ,Lupus Erythematosus, Systemic ,Immunology and Allergy ,skin and connective tissue diseases ,Intensive care medicine ,Pharmacology ,Autoimmune disease ,Biological Products ,Biological therapies ,business.industry ,medicine.disease ,Belimumab ,Biological Therapy ,Clinical trial ,Rituximab ,business ,medicine.drug - Abstract
Systemic lupus erythematosus (SLE) is a chronic autoimmune condition with unpredictable course, intermingled with flares and periods of remission. Although the prognosis of the disease has improved in the past decades, current therapies are still associated with treatment-related complications. Recently, there has been major progress in the understanding of the pathogenesis of SLE, paving the way for the development of new biological agents, potentially revolutionizing the treatment of SLE. This review summarizes available data on novel biological therapies for SLE, focusing on recent results from clinical trials. As a result of treatment strategies based upon an individualized therapeutic approach, it is hoped that the clinical view of SLE will change from a severe autoimmune disease to a condition in which significant damage, mortality and treatment related complications can be prevented in the majority of SLE patients.
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- 2015
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20. The risk of ischaemic stroke in primary antiphospholipid syndrome patients: a prospective study
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Massimo Radin, Irene Cecchi, Karen Schreiber, Maria José Cuadrado, Dario Roccatello, and Savino Sciascia
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Adult ,Male ,medicine.medical_specialty ,medicine.drug_class ,Hypercholesterolemia ,030204 cardiovascular system & hematology ,Risk Assessment ,Brain Ischemia ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Ischaemic stroke ,medicine ,Humans ,Prospective Studies ,Prospective cohort study ,Stroke ,030203 arthritis & rheumatology ,business.industry ,Anticoagulants ,Thrombosis ,Vitamin K antagonist ,Middle Aged ,medicine.disease ,Antiphospholipid Syndrome ,Primary antiphospholipid syndrome ,Surgery ,Venous thrombosis ,Neurology ,Cohort ,Female ,Neurology (clinical) ,Risk assessment ,business - Abstract
The most common neurological manifestation of antiphospholipid syndrome (APS) is ischaemic stroke. Identifying patients with APS at high risk for developing any thrombotic event remains a major challenge. In this study, the aim was to identify predictive factors of ischaemic stroke in a cohort of primary APS (PAPS) patients who presented with new onset symptoms suggestive of acute stroke.This prospective multicentre study included 36 consecutive PAPS patients who presented with new onset symptoms suggestive of an acute stroke. Patients were prospectively followed up for 12 months.In 10 (28%) out of 36 PAPS patients [mean age 41 years (SD 13.4), 70% female], the suspicion of an acute stroke was confirmed by brain magnetic resonance imaging. Sixty per cent of these patients were50 years old. Eight of the 10 patients had a history of previous venous thrombosis and were receiving vitamin K antagonist (VKA), with international normalized ratio target 2-3; one patient had a history of a previous arterial event receiving treatment with VKA target international normalized ratio 2-3 plus low dose aspirin; and one patient had a history of previous pregnancy morbidity receiving only low dose aspirin. Time in the therapeutic range for patients receiving VKA was 77.7% (SD 6.6%). Hypercholesterolaemia was significantly higher in patients with confirmed stroke compared to those without (P0.05). Similarly, a significantly higher rate of anti-β2 glycoprotein-I (β2GPI) antibodies (immunoglobulin G/immunoglobulin M; P0.05) and higher adjusted global APS score (aGAPSS) values were found in patients with a confirmed stroke [mean aGAPSS 8.9 (SD 4.7) vs. mean aGAPSS 6.4 (SD 2.5); P0.05].Patients with PAPS, including young patients, have a high risk of recurrent thrombosis despite anticoagulation treatment. A careful risk assessment is mandatory to identify patients at risk for recurrence.
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- 2017
21. Rate of Adverse Effects of Medium- to High-Dose Glucocorticoid Therapy in Systemic Lupus Erythematosus: A Systematic Review of Randomized Control Trials
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Savino Sciascia, Massimo Radin, Elisa Mompean, Dario Roccatello, and Maria José Cuadrado
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0301 basic medicine ,medicine.medical_specialty ,Pharmacology ,Gastroenterology ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Pharmacotherapy ,Randomized controlled trial ,Quality of life ,law ,Prednisone ,Internal medicine ,medicine ,Humans ,Lupus Erythematosus, Systemic ,Pharmacology (medical) ,Adverse effect ,Glucocorticoids ,Randomized Controlled Trials as Topic ,030203 arthritis & rheumatology ,Lupus erythematosus ,business.industry ,General Medicine ,medicine.disease ,030104 developmental biology ,Glucocorticoid therapy ,Meta-analysis ,Hyperglycemia ,Quality of Life ,business ,medicine.drug - Abstract
The efficacy of glucocorticoids (GCs) in treating systemic lupus erythematosus (SLE) is beyond doubt. However, GCs-related adverse effects (AEs) are multiple and serious. Despite the current available evidence suggesting to reduce daily doses of prednisone7.5 mg/day, or even to withdraw it, in the real-life practice, it is not uncommon to see patients receiving medium doses (up to 30 mg/day prednisone or equivalent) or high doses (≥30 mg/day).We systematically reviewed the literature with a priori strategy, to assess the rate of AEs related to medium or high doses of GCs in patients with SLE, analyzing randomized control trials with at least one of the treatment groups including GCs alone at medium or high doses.We found a rate of 9/100 patients/year for hyperglycemias/diabetes, 25/100 patients/year for infections, and 12/100 patients/year for avascular necrosis of the hip. Interestingly, when adjusting for GC dose and treatment duration, we observed no difference in terms of AEs comparing patients receiving medium versus high doses.In the era when treat-to-target strategies have been proposed in order to control SLE disease activity, improved health-related quality of life, and reduced morbidity and mortality, using GCs in a more restrictive way should be a goal to prevent major complications in patients with SLE.
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- 2017
22. Primary Prophylaxis in Patients With Positive Antiphospholipid Antibodies
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Maria José Cuadrado
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Lupus anticoagulant ,medicine.medical_specialty ,Pregnancy ,biology ,business.industry ,Obstetrics ,medicine.disease ,Thrombosis ,Antiphospholipid syndrome ,embryonic structures ,Foetal death ,biology.protein ,Medicine ,Gestation ,In patient ,Antibody ,business ,reproductive and urinary physiology - Abstract
Antiphospholipid syndrome (APS) is characterized clinically by the occurrence of either venous or arterial thrombosis and/or pregnancy morbidity (recurrent miscarriages in the first trimester, or foetal death in the second or third trimesters, or severe preeclampsia necessitating delivery of a premature infant before 34 weeks of gestation).
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- 2017
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23. Ubiquinol effects on antiphospholipid syndrome prothrombotic profile: A randomized, placebo-controlled trial
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Iván Arias de la Rosa, Lucía Fernández del Río, Maria del Carmen Abalos-Aguilera, Maria José Cuadrado, José A. González-Reyes, Irene Cecchi, Patricia Ruiz-Limon, José M. Villalba, Antonio Rodríguez-Ariza, Chary López-Pedrera, Eduardo Collantes-Estevez, Carlos Perez-Sanchez, P. Segui, Nuria Barbarroja, Maria Angeles Aguirre, Yolanda Jimenez-Gomez, Francisco Velasco, and Savino Sciascia
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0301 basic medicine ,Male ,Ubiquinone ,Placebo-controlled study ,030204 cardiovascular system & hematology ,medicine.disease_cause ,Monocytes ,chemistry.chemical_compound ,0302 clinical medicine ,oxidative stress ,Prospective Studies ,Cross-Over Studies ,ubiquinol ,Extracellular traps ,Vitamins ,Middle Aged ,Antiphospholipid Syndrome ,Thrombosis ,Mitochondria ,Female ,Antiphospholipid syndrome ,Inflammation ,Oxidative stress ,Ubiquinol ,Endothelium, Vascular ,Humans ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,Oxidation-Reduction ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,extracellular traps ,medicine.medical_specialty ,Oxidative phosphorylation ,Biology ,03 medical and health sciences ,Internal medicine ,Vascular ,medicine ,Endothelium ,thrombosis ,medicine.disease ,030104 developmental biology ,Endocrinology ,chemistry ,Immunology - Abstract
Objective— Antiphospholipid syndrome (APS) leukocytes exhibit an oxidative perturbation, directly linked to alterations in mitochondrial dynamics and metabolism. This disturbance is related to the patients’ prothrombotic status and can be prevented by in vitro treatment with coenzyme Q10. Our aim was to investigate short-term effects of in vivo ubiquinol (reduced coenzyme Q 10 [Q red ]) supplementation on markers related to inflammation and thrombosis in APS through a prospective, randomized, crossover, placebo-controlled trial. Approach and Results— Thirty-six patients with APS were randomized to receive Q red (200 mg/d) or placebo for 1 month. Thirty-three patients with APS completed the intervention, which increased plasma coenzyme Q 10 . Q red improved endothelial function and decreased monocyte expression of prothrombotic and proinflammatory mediators, inhibited phosphorylation of thrombosis-related protein kinases, and decreased peroxides and percentage of monocytes with depolarized mitochondria; mitochondrial size was increased, and mitochondrial biogenesis–related genes were upregulated. Q red ameliorated extruded neutrophil extracellular traps in neutrophils and downregulated peroxides, intracellular elastase, and myeloperoxidase. Nanostring microRNA profiling revealed 20 microRNAs reduced in APS monocytes, and 16 of them, with a preponderance of cardiovascular disease–related target mRNAs, were upregulated. Monocytes gene profiling showed differential expression of 29 atherosclerosis-related genes, 23 of them changed by Q red . Interaction networks of genes and microRNAs were identified. Correlation studies demonstrated co-ordinated effects of Q red on thrombosis and endothelial function–associated molecules. Conclusions— Our results highlight the potential of Q red to modulate the overexpression of inflammatory and thrombotic risk markers in APS. Because of the absence of clinically significant side effects and its potential therapeutic benefits, Q red might act as safe adjunct to standard therapies in APS. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT02218476
- Published
- 2017
24. 15th International Congress on Antiphospholipid Antibodies Task Force on Antiphospholipid Syndrome Treatment Trends Report
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Maria G Tektonidou, Mark Crowther, Maria José Cuadrado, Scott C. Woller, Rohan Willis, Doruk Erkan, Maria Gerosa, Michael D. Lockshin, David A. Garcia, Jane E. Salmon, Hannah Cohen, Ricard Cervera, Thomas L. Ortel, Anisur Rahman, Vittorio Pengo, Guillaume Canaud, and Danieli Andrade
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0301 basic medicine ,medicine.medical_specialty ,education ,Defibrotide ,03 medical and health sciences ,0302 clinical medicine ,immune system diseases ,Antiphospholipid syndrome ,Internal medicine ,International congress ,Medicine ,neoplasms ,health care economics and organizations ,030203 arthritis & rheumatology ,biology ,business.industry ,Task force ,medicine.disease ,Clopidogrel ,Cilostazol ,Clinical trial ,030104 developmental biology ,biology.protein ,Antibody ,business ,medicine.drug - Abstract
A challenge in antiphospholipid syndrome (APS) is to translate targeted therapies from animal and in vitro models to clinical trials. The 15th International Congress on Antiphospholipid Antibodies (aPL) Task Force on Treatment Trends summarized new developments in APS targeted treatment since the 14th International Congress on aPL (September 2013). The task force also discussed additional treatments and/or pathways that can be considered in the management of aPL-positive patients.
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- 2017
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25. Thrombotic Risk Assessment in Systemic Lupus Erythematosus: Validation of the Global Antiphospholipid Syndrome Score in a Prospective Cohort
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Giovanni Sanna, Savino Sciascia, Munther A. Khamashta, Dario Roccatello, Maria Laura Bertolaccini, Veronica Murru, and Maria José Cuadrado
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medicine.medical_specialty ,Lupus erythematosus ,business.industry ,Hazard ratio ,medicine.disease ,Thrombosis ,Confidence interval ,Surgery ,Rheumatology ,Antiphospholipid syndrome ,Internal medicine ,Relative risk ,medicine ,Risk assessment ,Prospective cohort study ,business - Abstract
Objective This study was performed to prospectively and independently validate the Global Antiphospholipid Syndrome Score (GAPSS), a system derived from the combination of independent risk factors for thrombosis, including antiphospholipid antibodies (aPL) and conventional cardiovascular risk factors. Methods The GAPSS was applied to 51 consecutive systemic lupus erythematosus patients, all positive for aPL and prospectively followed up for mean ± SD 32.94 ± 12.06 months. Of them, 48 were women with a mean ± SD age of 37.35 ± 12.15 years at entry. The GAPSS was calculated yearly for each patient by adding together the points corresponding to the risk factors. Results An increase in the GAPSS (entry versus last visit) was seen in patients who experienced vascular events (n = 4, mean ± SD 7.5 ± 4.36 versus 10.0 ± 5.4; P = 0.032). No changes were observed in those without thrombosis (n = 47, mean ± SD 8.28 ± 4.88 versus 7.13 ± 5.75; P = 0.24). An increase in the GAPSS during the followup was associated with a higher risk of vascular events (relative risk 12.30 [95% confidence interval (95% CI) 1.43–106.13], P = 0.004), and an increase of more than 3 points showed the best risk accuracy for vascular events (hazard ratio 48 [95% CI 6.90–333.85], P = 0.0001). The cumulative proportion of thrombosis-free individuals was lower in patients whose GAPSS was increased by 3 or more points (P = 0.0027). Conclusion We have prospectively demonstrated that GAPSS is a valid tool for accurate prediction of vascular events in SLE patients with aPL.
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- 2014
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26. Use of Intravenous Immunoglobulin in Patients With Active Vasculitis Associated With Concomitant Infection
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Ines Camara, Savino Sciascia, Yousuf Karim, Simone Baldovino, Joana Simoes, Dario Roccatello, and Maria José Cuadrado
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Adult ,Male ,Vasculitis ,MICROSCOPIC POLYANGIITIS ,medicine.medical_specialty ,CHURG-STRAUSS-SYNDROME, MICROSCOPIC POLYANGIITIS, SYSTEMIC VASCULITIDES, POLYARTERITIS-NODOSA, DISEASES, PROPHYLAXIS, THERAPY ,Churg-strauss syndrome ,Comorbidity ,Opportunistic Infections ,THERAPY ,PROPHYLAXIS ,Rheumatology ,medicine ,Humans ,In patient ,Aged ,Retrospective Studies ,Dose-Response Relationship, Drug ,biology ,Polyarteritis nodosa ,business.industry ,POLYARTERITIS-NODOSA ,Immunoglobulins, Intravenous ,Bacterial Infections ,Middle Aged ,medicine.disease ,Dermatology ,Treatment Outcome ,CHURG-STRAUSS-SYNDROME ,DISEASES ,Concomitant ,biology.protein ,SYSTEMIC VASCULITIDES ,Female ,Antibody ,Microscopic polyangiitis ,business - Published
- 2015
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27. Low-dose aspirin vs low-dose aspirin plus low-intensity warfarin in thromboprophylaxis: a prospective, multicentre, randomized, open, controlled trial in patients positive for antiphospholipid antibodies (ALIWAPAS)
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Frédéric Houssiau, Guillermo Ruiz-Irastorza, Munther A. Khamashta, Veronica Murru, María Victoria Egurbide, Caroline Gordon, Helena Martín, Paul T. Seed, Maria G Tektonidou, Anisur Rahman, Luisa Mico, Angeles Aguirre, María José Galindo, Neil McHugh, Mohammed Akil, Gerard Espinosa, Maria José Cuadrado, Maria Laura Bertolaccini, Antonio Gil, and Mary Carmen Amigo
- Subjects
Adult ,Male ,medicine.medical_specialty ,Randomization ,Kaplan-Meier Estimate ,Gastroenterology ,Autoimmune Diseases ,law.invention ,Rheumatology ,Randomized controlled trial ,Pregnancy ,law ,Internal medicine ,Outcome Assessment, Health Care ,medicine ,Humans ,Lupus Erythematosus, Systemic ,Pharmacology (medical) ,Longitudinal Studies ,Prospective Studies ,Aspirin ,Dose-Response Relationship, Drug ,business.industry ,Incidence (epidemiology) ,Hazard ratio ,Warfarin ,Anticoagulants ,Thrombosis ,Middle Aged ,Antiphospholipid Syndrome ,medicine.disease ,Surgery ,Pregnancy Complications ,Treatment Outcome ,Antibodies, Antiphospholipid ,Drug Therapy, Combination ,Female ,Observational study ,business ,Follow-Up Studies ,medicine.drug - Abstract
OBJECTIVES: The objectives of this study are to examine the efficacy and safety of low-dose aspirin (LDA) vs LDA plus low-intensity warfarin (LDA + W) in the primary thrombosis prevention of aPL-positive patients with SLE and/or obstetric morbidity and the role of clinical and serological markers in the development of thrombosis. METHODS: In this 5-year prospective, randomized, open, controlled trial, 166 patients with aPL were randomly assigned using a minimization protocol to receive treatment with LDA (n = 82) or LDA + W [international normalized ratio (INR) = 1.5] (n = 84). Sixty-six patients who declined randomization were followed up in an observational arm. Clinical and laboratory characteristics and medication side effects were recorded. RESULTS: There were no differences in the number of thromboses between patients treated with LDA (4/82) or LDA + W (4/84) [hazard ratio (HR) 1.07, 95% CI 0.27, 4.3]. The incidence of thrombosis in the randomized patients was 8/166 (1.8 events/100 person-years) (HR 1.07, 95% CI 0.27, 4.3) and in the observational arm was 7/66 (4.9 events/100 person-years) (HR 2.43, 95% CI 0.87, 6.79). Sixty-five of 66 patients included in the observational arm received LDA. None of the examined clinical or serological factors appeared to predict thrombosis. Medication side effects included mild gastrointestinal symptoms in the LDA group (n = 2) and bleeding in the LDA + W group (n = 11; 1 nasal and 10 menorrhagia). The risk difference for bleeding was 13% (CI 6, 20). CONCLUSION: No differences in the number of thromboses were observed between patients treated with LDA vs those treated with LDA + W. More episodes of bleeding were detected in the LDA + W group. The LDA + W regime was significantly less safe and not as acceptable as LDA alone. TRIAL REGISTRATION: ISRCTN81818945; http://isrctn.org/.
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- 2013
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28. Systemic Lupus Erythematosus: Clinical Aspects
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Maria José Cuadrado and Savino Sciascia
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business.industry ,Disease progression ,Lupus nephritis ,Disease ,medicine.disease ,Disease activity ,Organ damage ,Quality of life (healthcare) ,immune system diseases ,Immunology ,medicine ,skin and connective tissue diseases ,business ,Drug toxicity ,Anti-SSA/Ro autoantibodies - Abstract
Systemic lupus erythematosus (SLE) is a multisystem autoimmune disorder that results from a combination of genetic, environmental, and hormonal factors. The disease is characterized by a heterogeneous clinical presentation, a different course in different individuals, and a variability in the disease progression/fluctuations within the same patient. The clinical picture of SLE is extremely variable and may be related to disease activity, organ damage, drug toxicity, and quality of life.
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- 2016
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29. Emerging therapies in systemic lupus erythematous: From clinical trial to the real life
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William Chambers, Savino Sciascia, Huza Zhang, and Maria José Cuadrado
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0301 basic medicine ,medicine.medical_specialty ,Toxicology and Pharmaceutics (all) ,Disease ,Antibodies, Monoclonal, Humanized ,Pathogenesis ,03 medical and health sciences ,Biological agents ,0302 clinical medicine ,systemic lupus erythematosus ,immune system diseases ,medicine ,Immunologic Factors ,Lupus Erythematosus, Systemic ,Pharmacology (medical) ,Belimumab ,Rituximab ,Pharmacology, Toxicology and Pharmaceutics (all) ,General Pharmacology, Toxicology and Pharmaceutics ,skin and connective tissue diseases ,030203 arthritis & rheumatology ,Autoimmune disease ,Pharmacology ,Systemic lupus ,business.industry ,General Medicine ,medicine.disease ,Dermatology ,Clinical trial ,030104 developmental biology ,Rheumatoid arthritis ,Immunology ,business ,Immunosuppressive Agents ,medicine.drug - Abstract
Systemic lupus erythematous (SLE) is a chronic autoimmune disease characterised by multisystem involvement and a relapsing remitting course. SLE is a highly heterogeneous condition, with wide variations in both the presentation and severity of disease and the biological markers identified. The use of biologics in SLE has lagged behind that of other rheumatological conditions such as rheumatoid arthritis, in part due to the diverse clinical manifestations of SLE, making it difficult to design appropriate trials for novel treatments. As such, broad immunosuppressive treatment regimens are still widely used in SLE. Nevertheless, in recent years, elucidation of some aspects of SLE pathogenesis have allowed the development of therapies targeted at molecular mediators of SLE. This review provides an update of biological available therapies and those currently under development.
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- 2016
30. Potential Use of Statins in the Treatment of Antiphospholipid Syndrome
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Patricia Ruiz-Limon, M. Angeles Aguirre, Antonio Rodríguez-Ariza, Maria José Cuadrado, and Chary López-Pedrera
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Autoimmune disease ,medicine.medical_specialty ,Lupus anticoagulant ,biology ,business.industry ,Antiphospholipid Syndrome ,medicine.disease ,Thrombosis ,Rheumatology ,Venous thrombosis ,Immune system ,Antiphospholipid syndrome ,Internal medicine ,Immunology ,medicine ,biology.protein ,Humans ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,Antibody ,business - Abstract
Antiphospholipid syndrome (APS) is a disorder characterized by the association of arterial or venous thrombosis and/or pregnancy morbidity with the presence of antiphospholipid antibodies (anticardiolipin antibodies, lupus anticoagulant antibodies, and/or anti-β2-glycoprotein I antibodies). Several studies have contributed to uncovering the basis of antiphospholipid antibody pathogenicity, including the targeted cellular components, affected systems, involved receptors, intracellular pathways used, and the effector molecules that are altered in the process. Therapy for thrombosis traditionally has been based on long-term oral anticoagulation; however, bleeding complications and recurrence despite high-intensity anticoagulation can occur. Based on all the data obtained, new potential therapeutic agents have been proposed. Statins have a variety of direct effects on gene expression and the function of cells of both the innate and adaptive immune systems, many of which are related to blockade of GTPase isoprenylation. In APS, statins have multiple profound effects on monocyte, lymphocyte, and endothelial cell activities, all of which may contribute to thrombosis prevention in APS patients. Nevertheless, larger randomized trials are needed to validate the role of statins in the treatment of this autoimmune disease.
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- 2011
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31. The impact of hydroxychloroquine treatment on pregnancy outcome in women with antiphospholipid antibodies
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Savino Sciascia, Maria José Cuadrado, Beverley J. Hunt, E. Talavera-Garcia, Munther A. Khamashta, and G. Lliso
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0301 basic medicine ,Comorbidity ,Cohort Studies ,0302 clinical medicine ,Pregnancy ,Azathioprine ,Odds Ratio ,Lupus Erythematosus, Systemic ,Obstetrics ,antiphospholipid antibodies ,Pregnancy Outcome ,Obstetrics and Gynecology ,Antiphospholipid Syndrome ,Treatment Outcome ,Antibodies, Antinuclear ,Antirheumatic Agents ,Antibodies, Antiphospholipid ,Gestation ,Female ,Cohort study ,medicine.drug ,Hydroxychloroquine ,Adult ,medicine.medical_specialty ,Adolescent ,Prednisolone ,antiphospholipid syndrome ,hydroxychloroquine ,pregnancy ,03 medical and health sciences ,Young Adult ,Antiphospholipid syndrome ,medicine ,Humans ,Glucocorticoids ,Retrospective Studies ,030203 arthritis & rheumatology ,business.industry ,Case-control study ,Retrospective cohort study ,Odds ratio ,medicine.disease ,Delivery, Obstetric ,Surgery ,Pregnancy Complications ,030104 developmental biology ,Logistic Models ,Case-Control Studies ,Multivariate Analysis ,business - Abstract
Background Antiphospholipid syndrome is defined by the combination of thrombotic events and/or obstetric morbidity in patients who have tested positive persistently for antiphospholipid antibodies. With good treatment, approximately 70% of pregnant women with antiphospholipid syndrome will deliver a viable live infant. However, current management does not prevent all maternal, fetal, and neonatal complications of antiphospholipid syndrome. Objectives This observational, retrospective, single-center cohort study aimed to assess pregnancy outcome in women with antiphospholipid antibodies who were treated with hydroxychloroquine in addition to conventional treatment during pregnancy. Study Design One-hundred seventy pregnancies in 96 women with persistent antiphospholipid antibodies were analyzed: (1) 51 pregnancies that occurred in 31 women were treated with hydroxychloroquine for at least 6 months before pregnancy, and the therapy continued throughout gestation (group A); (2) 119 pregnancies that occurred in 65 women with antiphospholipid antibodies that were not treated with hydroxychloroquine were included as controls (group B). Results Hydroxychloroquine-treatment was associated with a higher rate of live births (67% group A vs 57% group B; P = .05) and a lower prevalence of antiphospholipid antibodies–related pregnancy morbidity (47% group A vs 63% B; P = .004). The association of hydroxychloroquine with a lower rate of any complication in pregnancy was confirmed after multivariate analysis (odds ratio, 2.2; 95% confidence interval, 1.2–136; P = .04). Fetal losses at >10 weeks of gestation (2% vs 11%; P = .05) and placenta-mediated complications (2% vs 11%; P = .05) were less frequent in group A than group B. Pregnancy duration was longer in group A than group B (27.6 [6-40] vs 21.5 [6-40] weeks; P = .03). There was a higher rate of spontaneous vaginal labor in hydroxychloroquine-treated women compared with group B (37.3% vs 14.3%; P = .01). Conclusions Despite the heterogeneity in the 2 groups in terms of systemic lupus erythematosus prevalence and previous pregnancy history, our results support the concept that women with antiphospholipid antibodies may benefit from treatment with hydroxychloroquine during pregnancy to improve pregnancy outcome. The addition of hydroxychloroquine to conventional treatment is worthy of further assessment in a proper designed randomized controlled trial.
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- 2015
32. The estimated frequency of Antiphospholipid antibodies in young adults with cerebrovascular events: A systematic review
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Laura Andreoli, Doruk Erkan, Maria Laura Bertolaccini, Savino Sciascia, Munther A. Khamashta, Giovanni Sanna, and Maria José Cuadrado
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Genetics and Molecular Biology (all) ,Pediatrics ,Anticardiolipin ,Antiphospholipid ,Biochemistry ,immune system diseases ,Ischaemic stroke ,Immunology and Allergy ,Young adult ,Stroke ,Anticardiolipin Antibodies ,Antiphospholipid Antibodies ,Antiphospholipid Syndrome ,Autoimmune Diseases ,education.field_of_study ,biology ,Ischemic Attack ,Transient ,Medicine (all) ,Middle Aged ,Ischemic Attack, Transient ,beta 2-Glycoprotein I ,Lupus Coagulation Inhibitor ,Antibodies, Antiphospholipid ,Antibody ,Adult ,medicine.medical_specialty ,Adolescent ,Antibodies, Anticardiolipin ,Autoantibodies ,Humans ,Young Adult ,Rheumatology ,Immunology ,Biochemistry, Genetics and Molecular Biology (all) ,Population ,MEDLINE ,General Biochemistry, Genetics and Molecular Biology ,Antibodies ,Antiphospholipid syndrome ,medicine ,In patient ,education ,neoplasms ,business.industry ,medicine.disease ,biology.protein ,business - Abstract
Around 10% of all thrombotic cerebrovascular events (CVE) occur in young population and in a large proportion of those the trigger remains undetermined. Antiphospholipid antibodies (aPL) are recognised risk factors for ischaemic stroke and recurrent thrombotic events; however, the frequency of aPL in young people with CVE is still an unresolved issue.To estimate the frequency of aPL in young adults with CVE and to determine whether aPL-positive young individuals are at greater risk of CVE when compared with individuals without aPL by systematically reviewing the literature.Medline reports published between 1970 and 2013 investigating the presence of aPL in young patients (50 years old) with CVE were included. The median frequency for positive aPL, including lupus anticoagulant, anticardiolipin antibodies (aCL) and antibodies against β2Glycoprotein I (anti-β2GPI), was calculated for stroke and transient ischaemic attacks.This systematic review is based on available data from 5217 patients and controls from 43 studies analysing the frequency of aPL in young patients with CVE. The overall aPL frequency was estimated as 17.4% (range 5%-56%) for any CVE, 17.2% (range 2%-56%) for stroke and 11.7% (range 2%-45%) for transient ischaemic attack (TIA). The presence of aPL increased the risk for CVE by 5.48-fold (95% CI 4.42 to 6.79). Based on available data, the frequency of aPL in young patients with CVE can be estimated at 17%, rising up to 22% for aCL in patients with stroke. The presence of aPL seems to confer a fivefold higher risk for stroke or TIA when compared with controls. However, variability in test reproducibility and cut-off definition still represent an important methodological limitation for the current diagnostic testing for aPL. These observations should be confirmed by appropriately designed population studies.
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- 2015
33. Long-Term Follow-Up in 128 Patients With Primary Antiphospholipid Syndrome
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José A. Gómez-Puerta, Helena Martín, Munther A. Khamashta, Mary-Carmen Amigo, Maria Angeles Aguirre, Maria José Cuadrado, María Teresa Camps, and Graham R. V. Hughes
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Adult ,Male ,medicine.medical_specialty ,Adolescent ,Anti-nuclear antibody ,Migraine Disorders ,Skin Diseases, Vascular ,Autoimmune Diseases ,Cohort Studies ,symbols.namesake ,Coombs test ,Pregnancy ,Internal medicine ,medicine ,Humans ,Lupus Erythematosus, Systemic ,Longitudinal Studies ,Fisher's exact test ,Aged ,Retrospective Studies ,Venous Thrombosis ,Lupus anticoagulant ,Univariate analysis ,Lupus erythematosus ,Systemic lupus erythematosus ,medicine.diagnostic_test ,business.industry ,Thrombosis ,General Medicine ,Odds ratio ,Middle Aged ,Antiphospholipid Syndrome ,medicine.disease ,Thrombocytopenia ,Surgery ,Abortion, Spontaneous ,Coombs Test ,Antibodies, Anticardiolipin ,Antibodies, Antinuclear ,Lupus Coagulation Inhibitor ,symbols ,Female ,Pulmonary Embolism ,business ,Follow-Up Studies - Abstract
We retrospectively studied a large cohort of patients with primary antiphospholipid syndrome (APS) from 4 different referral centers to analyze the clinical and serologic features and, specifically, to determine the number of patients going on to develop systemic lupus erythematosus (SLE) or other autoimmune disease after long-term follow-up. The study included 128 unselected patients with primary APS who fulfilled the Sapporo International Criteria from 4 different tertiary hospitals in the United Kingdom, Mexico, and Spain. The patients had attended the referral centers between January 1987 and July 2001. We reviewed clinical and serologic characteristics according to a pre-established protocol. We used univariate analysis with the chi-squared or Fisher exact test and logistic regression to analyze possible factors related to the coexistence of SLE and APS. Ninety-seven female and 31 male patients fulfilled the criteria, with a median age of 42 +/- 12 years (range, 16-79 yr), and with a mean follow-up of 9 +/- 3 years (range, 2-15 yr). The main manifestations included deep vein thrombosis in 62 patients (48%), arterial thrombosis in 63 (49%) patients, pregnancy loss in 177/320 (55%) cases, and pulmonary embolism in 37 (30%) patients. Other clinical manifestations were migraine in 51 (40%) patients, thrombocytopenia in 48 (38%), livedo reticularis in 47 (37%), and valvular disease in 27 (21%). Serologic findings were anticardiolipin antibodies (aCL) IgG positive in 110 (86%) patients, aCL IgM in 36 (39%), lupus anticoagulant in 71 (65%), antinuclear antibodies in 47 (37%), and positive Coombs test in 5 (4%) patients. During the follow-up and after a median disease duration of 8.2 years (range, 1-14 yr), 11 (8%) patients developed SLE, 6 (5%) developed lupus-like disease, and 1 (1%) developed myasthenia gravis. The remaining 110 patients (86%) continued to have primary APS. After the univariate analysis, a family history of lupus, the presence of Raynaud phenomenon, migraine, psychiatric features, multiple sclerosis-like features, hemolytic anemia, low C3 and C4, and Coombs positivity conferred a statistically significant risk for the subsequent development of SLE (p < 0.05). Only the presence of Coombs positivity had statistical significance (odds ratio, 66.4; 95% confidence interval, 1.6-2714; p = 0.027) after the logistic regression evaluation. The current study confirms that progression from primary APS to SLE or lupus-like disease is unusual, even after a long follow-up. Only 3 patients developed anti-dsDNA antibodies. The presence of a positive Coombs test might be a marker for the development of SLE in patients with primary APS.
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- 2005
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34. Central nervous system involvement in the antiphospholipid (Hughes) syndrome
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Giovanni Sanna, Munther A. Khamashta, G. R. V. Hughes, Maria Laura Bertolaccini, and Maria José Cuadrado
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Pathology ,medicine.medical_specialty ,Systemic disease ,Headache Disorders ,medicine.disease_cause ,Autoimmunity ,Central nervous system disease ,Rheumatology ,immune system diseases ,Antiphospholipid syndrome ,medicine ,Humans ,Pharmacology (medical) ,skin and connective tissue diseases ,Brain Diseases ,Lupus anticoagulant ,Epilepsy ,Lupus erythematosus ,business.industry ,Mental Disorders ,Antiphospholipid Syndrome ,medicine.disease ,Connective tissue disease ,Cerebrovascular Disorders ,Venous thrombosis ,Immunology ,business - Abstract
The antiphospholipid (Hughes) syndrome (APS) is characterized by arterial and/or venous thrombosis and pregnancy morbidity in the presence of anticardiolipin antibodies and/or lupus anticoagulant. APS can occur either as a primary disorder or secondary to a connective tissue disease, most frequently systemic lupus erythematosus. Central nervous system (CNS) involvement is one of the most prominent clinical manifestations of APS, and includes arterial and venous thrombotic events, psychiatric features and a variety of other non-thrombotic neurological syndromes. In this review we focus on the common and some of the less common CNS manifestations that have been reported in association with antiphospholipid antibodies.
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- 2003
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35. Treatment and monitoring of patients with antiphospholipid antibodies and thrombotic history (hughes syndrome)
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Maria José Cuadrado
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medicine.medical_specialty ,Rheumatology ,Recurrence ,Antiphospholipid syndrome ,Thromboembolism ,Internal medicine ,medicine ,Humans ,Intensive care medicine ,Stroke ,Lupus anticoagulant ,Aspirin ,business.industry ,Warfarin ,Anticoagulants ,Heparin, Low-Molecular-Weight ,Antiphospholipid Syndrome ,medicine.disease ,Thrombosis ,Surgery ,Acute Disease ,Drug Monitoring ,Complication ,business ,Immunosuppressive Agents ,medicine.drug - Abstract
Patients with Hughes (antiphospholipid) syndrome who develop an initial thrombosis have an increased risk of subsequent thrombotic events. Current therapy to prevent recurrent thrombosis is controversial. While it seems clear that anticoagulant treatment is a better option than anti-aggregants alone, there is no consensus regarding the duration and intensity of oral anticoagulation. The risk of bleeding, the main complication of anticoagulant treatment, and the need for frequent monitoring of the International Normalized Ratio to measure the anticoagulant effect of warfarin concern patients and physicians. In addition, there is some debate about the validity of the International Normalized Ratio in patients with lupus anticoagulant activity. The development of new therapies that target more specific pathogenic mechanisms is highly warranted.
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- 2002
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36. Mycophenolate mofetil for systemic lupus erythematosus refractory to other immunosuppressive agents
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P Alba, Mohammed Yousuf Karim, I C Abbs, G. R. V. Hughes, Munther A. Khamashta, Maria José Cuadrado, and David D'Cruz
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Adult ,Male ,Time Factors ,Cyclophosphamide ,medicine.medical_treatment ,Azathioprine ,Statistics, Nonparametric ,Mycophenolic acid ,Rheumatology ,medicine ,Humans ,Lupus Erythematosus, Systemic ,Pharmacology (medical) ,Treatment Failure ,skin and connective tissue diseases ,Autoimmune disease ,Chemotherapy ,Lupus erythematosus ,business.industry ,Racial Groups ,Middle Aged ,Mycophenolic Acid ,medicine.disease ,Connective tissue disease ,Proteinuria ,Methotrexate ,Immunosuppressive drug ,Antibodies, Antinuclear ,Immunology ,Female ,business ,Immunosuppressive Agents ,Follow-Up Studies ,medicine.drug - Abstract
Background. Mycophenolate mofetil (MMF) is an immunosuppressive drug widely used in solid organ transplantation, and it may play an increasing role in autoimmune disease. MMF has been introduced as a novel immunosuppressive agent in systemic lupus erythematosus (SLE), often in patients intolerant of or resistant to conventional immunosuppressive regimens. Methods. We studied 21 patients with SLE, most of whom had previously received courses of cyclophosphamide therapy and had also received courses of azathioprine or methotrexate. Indications for treatment included uncontrolled disease activity and worsening renal involvement. Results. MMF treatment resulted in reduced disease activity, as assessed by the SLEDAI (SLE disease activity index) (P= 0.0001) and decreased proteinuria (P= 0.027) while allowing a significant reduction in oral corticosteroid dose (P= 0.0001). Levels of complement factors C3 and C4 and anti-double-stranded DNA antibodies were not significantly affected. Conclusion. MMF appears to be a safe and effective alternative immunosuppressant for extra-renal and renal disease in SLE not responding to conventional immunosuppressive treatment.
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- 2002
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37. 14th International Congress on Antiphospholipid Antibodies: task force report on antiphospholipid syndrome treatment trends
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Hannah Cohen, Rohan Willis, Anisur Rahman, Maria José Cuadrado, Doruk Erkan, Maria G Tektonidou, Danieli Andrade, Michael D. Lockshin, Thomas L. Ortel, Adriana Danowski, Roger A. Levy, Cassyanne L. Aguiar, and Jane E. Salmon
- Subjects
medicine.medical_specialty ,Immunology ,immune system diseases ,Antiphospholipid syndrome ,Heparin-induced thrombocytopenia ,Immunology and Allergy ,Medicine ,Humans ,Intensive care medicine ,Rivaroxaban ,business.industry ,Warfarin ,Anticoagulants ,Thrombosis ,Eculizumab ,medicine.disease ,Antiphospholipid Syndrome ,Clinical trial ,Clinical research ,Factor Xa ,Antibodies, Antiphospholipid ,Rituximab ,business ,medicine.drug ,Hydroxychloroquine - Abstract
Antiphospholipid Syndrome (APS) is characterized by vascular thrombosis and/or pregnancy morbidity occurring in patients with persistent antiphospholipid antibodies (aPL). The primary objective of the APS Treatment Trends Task Force, created as part of the 14th International Congress on aPL, was to systematically review the potential future treatment strategies for aPL-positive patients. The task force chose as future clinical research directions: a) determining the necessity for controlled clinical trials in venous thromboembolism with the new oral direct thrombin or anti-factor Xa inhibitors pending the results of the ongoing rivaroxaban in APS (RAPS) trial, and designing controlled clinical trials in other forms of thrombotic APS; b) systematically analyzing the literature as well as aPL/APS registries, and creating specific registries for non-warfarin/heparin anticoagulants; c) increasing recruitment for an ongoing primary thrombosis prevention trial, and designing secondary thrombosis and pregnancy morbidity prevention trials with hydroxychloroquine; d) determining surrogate markers to select patients for statin trials; e) designing controlled studies with rituximab and other anti-B-cell agents; f) designing mechanistic and clinical studies with eculizumab and other complement inhibitors; and g) chemically modifying peptide therapy to improve the half-life and minimize immunogenicity. The report also includes recommendations for clinicians who consider using these agents in difficult-to-manage aPL-positive patients.
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- 2014
38. Renal involvement in antiphospholipid syndrome
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Dario Roccatello, Maria José Cuadrado, Munther A. Khamashta, and Savino Sciascia
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Adult ,Pathology ,medicine.medical_specialty ,Thrombotic microangiopathy ,Lupus nephritis ,anticardiolipin antibodies ,urologic and male genital diseases ,Kidney ,Renal Veins ,End stage renal disease ,systemic lupus erythematosus ,immune system diseases ,Antiphospholipid syndrome ,Pregnancy ,vascular access occlusion ,medicine ,Humans ,Lupus Erythematosus, Systemic ,Lupus erythematosus ,business.industry ,Thrombosis ,Middle Aged ,medicine.disease ,Antiphospholipid Syndrome ,Lupus Nephritis ,Transplantation ,medicine.anatomical_structure ,Nephrology ,Infarction ,Antibodies, Antiphospholipid ,Kidney Failure, Chronic ,Female ,Kidney Diseases ,Warfarin ,business ,Nephritis - Abstract
Antiphospholipid syndrome (APS) is an autoimmune disease defined by the presence of arterial or venous thrombotic events and/or pregnancy morbidity in patients who test positive for antiphospholipid antibodies (aPLs). APS can be isolated (known as primary APS) or associated with other autoimmune diseases, such as systemic lupus erythematosus (SLE; known as secondary APS). The kidney is a major target organ in APS and renal thrombosis can occur at any level within the vasculature of the kidney (renal arteries, intrarenal arteries, glomerular capillaries and renal veins); events reflect the site and size of the involved vessels. Histological findings vary widely, including ischaemic glomeruli and thrombotic lesions without glomerular or arterial immune deposits on immunofluorescence. Renal prognosis is affected by the presence of aPLs in patients with lupus nephritis and can be poor. In patients with SLE and aPLs, biopsy should be performed because inflammatory and thrombotic lesions require different therapeutic approaches. Renal involvement in patients with definite APS is treated by anticoagulation with long-term warfarin. The range of renal manifestations associated with APS is broadening and, therefore, aPLs have increasing relevance in end-stage renal disease, transplantation and pregnancy.
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- 2014
39. HUGHES (ANTIPHOSPHOLIPID) SYNDROME
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Maria José Cuadrado and Graham R. V. Hughes
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Autoimmune disease ,medicine.medical_specialty ,Pathology ,Vascular disease ,business.industry ,Antithrombin III deficiency ,medicine.disease ,Dermatology ,Thrombosis ,Venous thrombosis ,Rheumatology ,Antiphospholipid syndrome ,Immunopathology ,medicine ,Platelet ,business - Abstract
Hughes (antiphospholipid) syndrome (APS) is a noninflammatory autoimmune disease. The most critical pathologic process is thrombosis, which results in most of the clinical features suffered by these patients. Recurrent thrombosis together with an adverse pregnancy history and the presence of antiphospholipid antibodies (aPL) defines the syndrome. Arterial and venous thrombosis can be present in APS, distinguishing this from other prothrombotic states such as protein C, S, or antithrombin III deficiency, where only venous thrombosis occurs. Any organ and any size of vessel (small, medium, or large) can be affected in this disorder; thus, the range of clinical features is extremely wide. In this review, we try to focus on the common and some of the less common clinical manifestations.
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- 2001
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40. Natural immune response involving anti-endothelial cell antibodies in normal and lupus pregnancy
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Munther A. Khamashta, Maria José Cuadrado, Graham R. V. Hughes, Maria Laura Bertolaccini, and L L F Mendonça
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medicine.medical_specialty ,Fetus ,Pregnancy ,Lupus erythematosus ,Systemic lupus erythematosus ,biology ,business.industry ,Immunology ,medicine.disease ,Preeclampsia ,Endocrinology ,Rheumatology ,Internal medicine ,Immunopathology ,medicine ,biology.protein ,Immunology and Allergy ,Gestation ,Pharmacology (medical) ,Antibody ,business - Abstract
OBJECTIVE To determine whether immunoglobulins with affinity for the vascular endothelium displayed any distinguishing behavior during normal and systemic lupus erythematosus (SLE) pregnancy. We also attempted to verify whether isotype expression of anti-endothelial cell antibodies (AECA) would have any predictive value for pregnancy outcome. METHODS Sera from 38 pregnant patients with SLE, 68 normal pregnant women, and 84 nonpregnant healthy controls were studied. IgM- and IgG-AECA were determined by cellular enzyme-linked immunosorbent assay using fixed cultured human umbilical vein endothelial cells. RESULTS A significantly higher level of IgM-AECA was found during normal pregnancy compared with that in healthy nonpregnant controls (mean +/- SD 39 +/- 12% versus 21 +/- 12%; P < 0.0001). Most pregnant patients with SLE did not have increased titers of IgM-AECA, but instead had levels similar to those found in healthy nonpregnant controls (23 +/- 12%; P not significant). The lowest levels of IgM-AECA in lupus pregnancy were associated with preeclampsia (odds ratio 16, P < 0.005). Conversely, IgG-AECA levels were significantly higher in the serum of normal pregnant women and pregnant SLE patients than in the serum of healthy nonpregnant controls (24 +/- 7% and 24 +/- 14% versus 9 +/- 7%; P < 0.0001). CONCLUSION Our results indicate that an active immune response occurs during pregnancy. This response involves increased activity of AECA, suggesting a role of autoantibodies as a possible contributing factor toward fetal tolerance. Our observations further indicate that impaired immune regulation, such as diminished levels of serum IgM-AECA detected in SLE patients, might contribute to the impaired reproductive function commonly found in SLE.
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- 2000
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41. The anti-phospholipid antibody syndrome (Hughes syndrome): therapeutic aspects
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Munther A. Khamashta and Maria José Cuadrado
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Abortion, Habitual ,Aspirin ,Pediatrics ,medicine.medical_specialty ,business.industry ,medicine.drug_class ,Anticoagulant ,Warfarin ,Thrombosis ,Antiphospholipid Syndrome ,medicine.disease ,Thrombophilia ,Thrombocytopenia ,Surgery ,Venous thrombosis ,Rheumatology ,Pregnancy ,Recurrent miscarriage ,medicine ,Humans ,Female ,business ,Stroke ,medicine.drug - Abstract
Despite the enormous amount of work focused on the pathogenesis and clinical manifestations of the Hughes or anti-phospholipid syndrome (APS), there is little published on management. Usually, the diagnosis of APS is made after the first thrombotic event, when a thrombophilia screen is performed. These patients have a high risk of recurrent thromboses and current therapy centres on the use of thromboprophylaxis with warfarin. However, a number of clinical questions keep recurring: do arterial and venous thrombosis require the same intensity of anti-coagulation? When should warfarin be stopped? Should patients who develop thrombosis when other risk factors (oral contraceptive pill, prolonged resting etc.) are present be treated like those without any risk factors but the presence of anti-phospholipid antibodies (aPL)? How to manage a patient with recurrent thrombosis despite a high intensity anti-coagulation (International normalized ratio (INR) between 3.0-4.0)? Since many of the patients with aPL are fertile women, a substantial group of patients are diagnosed after recurrent pregnancy loss. Low-dose aspirin for those patients without previous thrombosis and aspirin plus heparin for patients with a history of thrombotic events are the current therapeutic options. However, some questions remain unanswered: does the addition of heparin to low-dose aspirin in women with first trimester recurrent miscarriage but without previous thrombosis improve foetal outcome over and above aspirin alone? Which is the best therapeutic regime during pregnancy for patients with aPL-associated stroke? When should high-dose intravenous gammaglobulin be considered? Finally, very little is known about the risk of thrombosis in individuals positive for aPL but still free of thrombosis. Should these individuals receive any treatment? If so, which one? In this review we attempt to address some of these questions taking into account available data from retrospective and prospective studies and our own clinical experience.
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- 2000
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42. The Future Potential of Biosimilars Targeting B-Cells
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Chary López-Pedrera, Savino Sciascia, Dario Roccatello, and Maria José Cuadrado
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Reference product ,Risk analysis (engineering) ,Manufacturing process ,Biologic therapies ,Data Protection Act 1998 ,A protein ,Biosimilar ,Business ,Marketing authorization ,Healthcare system - Abstract
The patent and regulatory data protection periods for the first and second waves of biological agents based on recombinant proteins have started to expire, leaving open the potential for development and regulatory approval of 1 or more “similar” versions of these biologic therapies, termed biosimilars in Europe (BS)—the term that will be used in this chapter—subsequent entry biologics in Canada, or follow-on-biologics in the USA. The development of BS therapies could lead to a substantial saving for patients/health systems and, therefore, increased availability of effective treatments. BSs are similar but not identical to their reference products, because their chemical characteristics are directly related to the manufacturing process, which cannot be precisely duplicated. An exact replica of a protein molecule is extremely difficult if not impossible. Thus, major concerns about short- and long-term safety and efficacy have been raised and should be addressed in the approval process by regulatory agencies. For these reason, BSs require an approach to grant the marketing authorization, different from generics.
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- 2013
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43. Management of infection in systemic lupus erythematosus
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Maria José Cuadrado, Mohammed Yousuf Karim, and Savino Sciascia
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medicine.drug_class ,Antibiotics ,Opportunistic Infections ,Systemic autoimmune disease ,Rheumatology ,Risk Factors ,immune system diseases ,medicine ,Humans ,Lupus Erythematosus, Systemic ,skin and connective tissue diseases ,Autoantibodies ,Vaccines ,Systemic lupus erythematosus ,biology ,business.industry ,Risk of infection ,Vaccination ,Bacterial Infections ,medicine.disease ,Virus Diseases ,Intravenous Immunoglobulins ,Immunology ,biology.protein ,Antibody ,business ,Autoantibody production ,Immunosuppressive Agents - Abstract
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterised by abnormal autoantibody production and clearance. This immunological background has been suggested to play a role in the susceptibility of SLE patients to infection. Moreover, drugs (most of them immunosuppressive or immunomodulating agents) used in the treatment of moderate and severe lupus give rise to a tendency for infections, including opportunistic ones. Infections may mimic the exacerbations of SLE, leading to confusion over the diagnosis and appropriate treatment. Despite increased awareness of this problem, infections remain a major source of morbidity and mortality in SLE. There are various strategies which can be applied to try and reduce the risk of infection in SLE patients. Options include vaccinations, antibiotic/antiviral prophylaxis and intravenous immunoglobulins.
- Published
- 2013
44. The Management of Thrombosis in the Antiphospholipid-Antibody Syndrome
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Beverley J. Hunt, Nick Taub, Maria José Cuadrado, Munther A. Khamashta, Graham R. V. Hughes, and Fedza Mujic
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Adult ,Male ,medicine.medical_specialty ,Adolescent ,medicine.drug_class ,Recurrence ,Internal medicine ,medicine ,Humans ,Lupus Erythematosus, Systemic ,Vein ,Retrospective Studies ,Aspirin ,Lupus erythematosus ,Vascular disease ,business.industry ,Anticoagulant ,Warfarin ,Anticoagulants ,Thrombosis ,General Medicine ,Middle Aged ,Antiphospholipid Syndrome ,medicine.disease ,Connective tissue disease ,Surgery ,medicine.anatomical_structure ,Female ,business ,Follow-Up Studies ,medicine.drug - Abstract
The antiphospholipid-antibody syndrome is a thrombophilic disorder in which venous or arterial thrombosis, or both, may occur in patients with antiphospholipid antibodies. The optimal treatment of these patients is unclear. We assessed the efficacy of warfarin, low-dose aspirin, or both in the secondary prevention of thrombosis in patients with the syndrome.One hundred forty-seven patients (124 [84 percent] of whom were female) with the antiphospholipid-antibody syndrome and a history of thrombosis were studied retrospectively. The syndrome was primary in 62 patients and was associated with systemic lupus erythematosus in 66 patients and lupus-like disease in 19. Each patient's history was reviewed.One hundred one patients (69 percent) had a total of 186 recurrences of thrombosis. The median time between the initial thrombosis and the first recurrence was 12 months (range, 0.5 to 144 months). Treatment with high-intensity warfarin (producing an international normalized ratio ofor = 3) with or without low-dose aspirin (75 mg per day) was significantly more effective (P0.001 by the log-rank test) than treatment with low-intensity warfarin (producing an international normalized ratio of3) with or without low-dose aspirin or treatment with aspirin alone in preventing further thrombotic events (recurrence rates per patient-year, 0.013, 0.23, and 0.18, respectively). The rate of recurrence of thrombosis was highest (1.30 per patient-year) during the first six months after the cessation of warfarin therapy. Complications involving bleeding occurred in 29 patients during warfarin therapy and were severe in 7 (0.071 and 0.017 occurrence per patient-year, respectively).The risk of recurrent thrombosis in patients with the antiphospholipid-antibody syndrome is high. Long-term anticoagulation therapy in which the international normalized ratio is maintained at or above 3 is advisable in these patients.
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- 1995
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45. Mitochondrial dysfunction in antiphospholipid syndrome: implications in the pathogenesis of the disease and effects of coenzyme Q(10) treatment
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Maria José Cuadrado, P. Segui, Patricia Ruiz-Limon, Francisco Velasco, Husam Khraiwesh, Maria Laura Bertolaccini, José A. González-Reyes, Carlos Perez-Sanchez, José M. Villalba, Antonio Rodríguez-Ariza, Maria Angeles Aguirre, Munther A. Khamashta, Nuria Barbarroja, Eduardo Collantes-Estevez, and Chary López-Pedrera
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Adult ,Male ,medicine.medical_specialty ,Ubiquinone ,Immunology ,Oxidative phosphorylation ,Biology ,Mitochondrion ,medicine.disease_cause ,Biochemistry ,Monocytes ,Proinflammatory cytokine ,Pathogenesis ,Tissue factor ,Antiphospholipid syndrome ,Internal medicine ,medicine ,Humans ,Inflammation ,Thrombosis ,Cell Biology ,Hematology ,Middle Aged ,medicine.disease ,Antiphospholipid Syndrome ,Mitochondria ,Peroxides ,Oxidative Stress ,Endocrinology ,Coenzyme Q – cytochrome c reductase ,Case-Control Studies ,Immunoglobulin G ,Antibodies, Antiphospholipid ,Female ,Oxidative stress ,Biomarkers - Abstract
The exact mechanisms underlying the role of oxidative stress in the pathogenesis and the prothrombotic or proinflammatory status of antiphospholipid syndrome (APS) remain unknown. Here, we investigate the role of oxidative stress and mitochondrial dysfunction in the proatherothrombotic status of APS patients induced by IgG-antiphospholipid antibodies and the beneficial effects of supplementing cells with coenzyme Q10 (CoQ10). A significant increase in relevant prothrombotic and inflammatory parameters in 43 APS patients was found compared with 38 healthy donors. Increased peroxide production, nuclear abundance of Nrf2, antioxidant enzymatic activity, decreased intracellular glutathione, and altered mitochondrial membrane potential were found in monocytes and neutrophils from APS patients. Accelerated atherosclerosis in APS patients was found associated with their inflammatory or oxidative status. CoQ10 preincubation of healthy monocytes before IgG-antiphospholipid antibody treatment decreased oxidative stress, the percentage of cells with altered mitochondrial membrane potential, and the induced expression of tissue factor, VEGF, and Flt1. In addition, CoQ10 significantly improved the ultrastructural preservation of mitochondria and prevented IgG-APS–induced fission mediated by Drp-1 and Fis-1 proteins. In conclusion, the oxidative perturbation in APS patient leukocytes, which is directly related to an inflammatory and pro-atherothrombotic status, relies on alterations in mitochondrial dynamics and metabolism that may be prevented, reverted, or both by treatment with CoQ10.
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- 2012
46. Catastrophic antiphospholipid syndrome (CAPS)
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Chary López-Pedrera, Savino Sciascia, Maria José Cuadrado, and Dario Roccatello
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IVIG ,Catastrophic illness ,Pediatrics ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,catastrophic antiphospholipid syndrome ,Prognosis ,medicine.disease ,Catastrophic antiphospholipid syndrome ,Surgery ,Rare Diseases ,Rheumatology ,Antiphospholipid syndrome ,Clinical evidence ,Humans ,Medicine ,Organ involvement ,Plasmapheresis ,Small vessel ,Catastrophic Illness ,business ,High titre ,antiphospholipid syndrome - Abstract
Catastrophic antiphospholipid syndrome (CAPS) is a very severe variant of the classic APS, characterised by clinical evidence of multiple organ involvement developing over a very short period of time, histopathological evidence of multiple small vessel occlusions and laboratory confirmation of the presence of antiphospholipid antibodies (aPL), usually in high titre. Although patients with catastrophic APS represent less than 1% of all patients with APS, this is usually a life-threatening condition. In this article, we aimed to review the state-of-the art about current knowledge in pathogenesis, clinical manifestations, diagnosis and treatment strategies in CAPS.
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- 2012
47. Catastrophic Antiphospholipid Syndrome
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Giovanni Sanna, Maria José Cuadrado, Maria Laura Bertolaccini, and Munther A. Khamashta
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medicine.medical_specialty ,Pregnancy ,Lupus anticoagulant ,business.industry ,medicine.medical_treatment ,Mortality rate ,Catastrophic antiphospholipid syndrome ,medicine.disease ,Thrombosis ,Venous thrombosis ,immune system diseases ,Antiphospholipid syndrome ,Internal medicine ,medicine ,Cardiology ,Plasmapheresis ,skin and connective tissue diseases ,business - Abstract
Antiphospholipid syndrome (APS) is characterized by the development of arterial and/or venous thrombosis and/or pregnancy morbidity in the presence of antiphospholipid antibodies (aPL) anticardiolipin (aCL), anti-β2-glycoprotein I (anti-β2GPI), and lupus anticoagulant (LA). Catastrophic antiphospholipid syndrome (CAPS) is a very severe variant of the classic APS, with predominant and extensive small-vessels occlusion that causes multiple organs thrombosis. Multiple thrombotic events occur in a short period of time and frequently lead to a life-threatening condition because of multiorgan failure. The mortality rate is high, but an early diagnosis and treatment with anticoagulation, corticosteroids, plasma exchange, and intravenous immunoglobulin (IVIG) may reduce this rate.
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- 2011
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48. Global effects of fluvastatin on the prothrombotic status of patients with antiphospholipid syndrome
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Maria José Cuadrado, Patricia Ruiz-Limon, Carlos Perez-Sanchez, Munther Khasmahta, Antonio Rodríguez-Ariza, Chary López-Pedrera, Francisco Velasco, Nuria Barbarroja, Maria Angeles Aguirre, Ines-Carmen Rodriguez-García, Paula Buendía, and Eduardo Collantes-Estevez
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Adult ,Male ,Proteomics ,Vascular Endothelial Growth Factor A ,medicine.medical_specialty ,Indoles ,Immunology ,Receptors, Proteinase-Activated ,p38 Mitogen-Activated Protein Kinases ,General Biochemistry, Genetics and Molecular Biology ,Monocytes ,Proinflammatory cytokine ,Thromboplastin ,Fatty Acids, Monounsaturated ,chemistry.chemical_compound ,Tissue factor ,Rheumatology ,Antiphospholipid syndrome ,Internal medicine ,medicine ,Immunology and Allergy ,Humans ,Platelet ,Phosphorylation ,Fluvastatin ,Cells, Cultured ,business.industry ,NF-kappa B ,Thrombosis ,Middle Aged ,medicine.disease ,Antiphospholipid Syndrome ,Vascular endothelial growth factor ,Endocrinology ,chemistry ,Case-Control Studies ,Protein prenylation ,Female ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,business ,Annexin A2 ,medicine.drug - Abstract
ObjectiveNumerous mechanisms have been proposed to explain the thrombotic/proinflammatory tendency of antiphospholipid syndrome (APS) patients. Prothrombotic monocyte activation by antiphospholipid antibodies involves numerous proteins and intracellular pathways. The anti-inflammatory, anticoagulant and immunoregulatory effects of statins have been aimed as a therapeutic tool in APS patients. This study delineates the global effects of fluvastatin on the prothrombotic tendency of monocytes from APS patients.MethodsForty-two APS patients with thrombosis and 35 healthy donors were included in the study. APS patients received 20 mg/day fluvastatin for 1 month. Blood samples were obtained before the start, at the end and 2 months after the end of treatment.ResultsAfter 1 month of treatment, monocytes showed a significant inhibition of tissue factor, protein activator receptors 1 and 2, vascular endothelial growth factor and Flt1 expression that was related to the inhibition of p38 mitogen-activated protein kinase (MAPK) and nuclear factor kappa B/Rel DNA-binding activity. Proteomic analysis showed proteins involved in thrombotic development (annexin II, RhoA and protein disulphide isomerase) with altered expression after fluvastatin administration. In-vitro studies indicated that the inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase by fluvastatin might inhibit protein prenylation and MAPK activation.ConclusionThe data from this study support the belief that fluvastatin has multiple profound effects in monocyte activity, which might contribute to thrombosis prevention in APS patients.
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- 2010
49. Differential expression of protease-activated receptors in monocytes from patients with primary antiphospholipid syndrome
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Paula Buendía, Eduardo Collantes-Estevez, Francisco Velasco, Chary López-Pedrera, Maria Angeles Aguirre, Patricia Ruiz-Limon, Nuria Barbarroja, Maria José Cuadrado, and Munther A. Khamashta
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Adult ,Male ,medicine.medical_specialty ,Lipopolysaccharide ,Immunology ,Receptors, Proteinase-Activated ,Peripheral blood mononuclear cell ,Immunoglobulin G ,Monocytes ,Thromboplastin ,Tissue factor ,chemistry.chemical_compound ,Rheumatology ,Internal medicine ,medicine ,Immunology and Allergy ,Humans ,Pharmacology (medical) ,Platelet ,Receptor ,biology ,Reverse Transcriptase Polymerase Chain Reaction ,Monocyte ,Antibodies, Monoclonal ,Thrombosis ,Receptor Cross-Talk ,Middle Aged ,Antiphospholipid Syndrome ,Flow Cytometry ,Endocrinology ,medicine.anatomical_structure ,chemistry ,Antibodies, Anticardiolipin ,Monoclonal ,biology.protein ,RNA ,Female - Abstract
Objective To investigate the expression of protease-activated receptors (PARs), their potential regulation by anticardiolipin antibodies (aCL), and their association with the expression of other molecules relevant to thrombosis in monocytes obtained from 62 patients with primary antiphospholipid syndrome (APS). Methods Monocytes were isolated from peripheral blood mononuclear cells by magnetic depletion of nonmonocytes. Expression of tissue factor (TF) and PARs 1–4 genes was measured by quantitative real-time reverse transcription–polymerase chain reaction. Cell surface TF and PARs 1–4 expression was analyzed by flow cytometry. For in vitro studies, purified normal monocytes were incubated with purified APS patient IgG, normal human serum IgG, or lipopolysaccharide, in the presence or absence of specific monoclonal antibodies anti–PAR-1 (ATAP2) or anti–PAR-2 (SAM11) to test the effect of blocking the active site of PAR-1 or PAR-2. Results Analysis of both mRNA and protein for the 4 PARs revealed significantly increased expression of PAR-2 as compared with the control groups. PAR-1 was significantly overexpressed in APS patients with thrombosis and in the control patients with thrombosis but without APS. PAR-3 expression was not significantly altered. PAR-4 expression was absent in all groups analyzed. In addition, we demonstrated a correlation between the levels of PAR-2 and the titers of IgG aCL, as well as parallel behavior of TF and PAR-2 expression. In vitro, IgG from APS patients significantly increased monocyte expression of PAR-1 and PAR-2. Inhibition studies suggested that there was direct cross-talk between TF and PAR-2, such that inhibition of PAR-2 prevented the aCL-induced expression of TF. Conclusion These results provide the first demonstration of increased expression of PARs in monocytes from patients with APS. Thus, PAR antagonists might have therapeutic potential as antithrombotic agents in APS.
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- 2010
50. Accelerated Atherosclerosis in Systemic Lupus Erythematosus: Role of Proinflammatory Cytokines and Therapeutic Approaches
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Nuria Barbarroja, Maria José Cuadrado, Maria Angeles Aguirre, and Chary López-Pedrera
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Health, Toxicology and Mutagenesis ,lcsh:Biotechnology ,lcsh:Medicine ,Review Article ,lcsh:Chemical technology ,lcsh:Technology ,Proinflammatory cytokine ,lcsh:TP248.13-248.65 ,Genetics ,medicine ,Macrophage ,Humans ,Lupus Erythematosus, Systemic ,lcsh:TP1-1185 ,B-cell activating factor ,Molecular Biology ,B cell ,Autoimmune disease ,Lupus erythematosus ,lcsh:T ,business.industry ,lcsh:R ,Autoantibody ,General Medicine ,medicine.disease ,Atherosclerosis ,Immune complex ,medicine.anatomical_structure ,Immunology ,Molecular Medicine ,Cytokines ,business ,Biotechnology - Abstract
Systemic lupus erythematosus (SLE), a chronic multisystem autoimmune disease with a broad range of clinical manifestations, is associated with accelerated atherosclerosis (AT) and increased risk of cardiovascular complications. Relevant factors directly influencing the development of AT comprise immune complex generation, complement activation, and changes in the production and activity of a complex network of cytokines, including type I and II interferons, B lymphocyte stimulator (BLyS), TNFα, IL-6, IL-17 and migration macrophage inhibitor (MIF). Autoantibodies, also responsible for cytokine expression and activation, play a supplementary key role in the development of AT. Genomic and proteomic studies have contributed to the discovery of genes and proteins involved in AT, including some that may be suitable to be used as biomarkers. All that data has allowed the development of new drugs, most of them evaluated in clinical trials: inhibitors of IFN and TNFα, B cell directed therapies, synthetic oligodeoxynucleotides, intravenous immunoglobulin, or statins. The focus of the present paper is to summarize recent evidence showing the role of cytokines in the development of AT in SLE and the rationale, and safety concerns, in the use of combined therapy to prevent AT and cardiovascular disease.
- Published
- 2010
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