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Danza A.,University of the Republic of Uruguay | Danza A.,University of the Basque Country | Ruiz-Irastorza G.,University of the Basque Country | Khamashta M.,Lupus Research Unit
Medicina Clinica | Year: 2016

Systemic autoimmune diseases especially affect young women during childbearing age. The aim of this review is to update systemic lupus erythematosus, antiphospholipid syndrome and systemic sclerosis management during pregnancy.These diseases present variable maternal and fetal risks. Studies show that an appropriate disease control and a reasonable remission period prior to pregnancy are associated with satisfactory obstetric outcomes. Antiphospholipid autoantibodies profile, anti-Ro/anti-La antibodies, pulmonary pressure and activity evaluation are crucial to assess the pregnancy risk.Monitoring requires a multidisciplinary team, serial analytic controls and Doppler ultrasound of maternal and fetal circulation. Evaluation of the activity of the disease is essential. © 2016 Elsevier España, S.L.U. Source

Manson J.J.,University College London | Mills K.,Institute for Child Health | Jury E.,University College London | Mason L.,University College London | And 6 more authors.
Lupus Science and Medicine | Year: 2014

Introduction: The tertiary structure of normal podocytes prevents protein from leaking into urine. Patients with lupus nephritis (LN) develop proteinuria, and kidney biopsies from these patients display a number of podocyte abnormalities including retraction of podocyte processes. Autoantibodies have been shown to deposit in the kidneys of patients and mice with LN and are believed to play a key role in causing renal inflammation and dysfunction. The objective of this research was to study the effects of IgG antibodies from patients with LN on cultured human podocytes. Methods: We exposed a human podocyte cell line to heat-inactivated (HI) plasma and purified polyclonal IgG from the following groups of subjects; patients with LN, patients with lupus without nephritis, patients with rheumatoid arthritis and healthy controls. We measured expression and intracellular distribution of podocyte-specific proteins and global phosphorylation of tyrosine. We then used mass spectrometry to identify the major protein targets of this phosphorylation. Results: HI LN plasma did not alter expression or cellular distribution of podocyte-specific proteins but caused a significant reduction in podocyte protein tyrosine phosphorylation compared with plasma from healthy controls (p=0.0008). This result was replicated using purified IgG but was not seen with plasma from rheumatoid arthritis or non-renal lupus patients. The dominant tyrosine phosphorylated protein in podocytes was 55 kDa in size and was identified as tubulin. Conclusions: Since tubulin is an important component of podocyte major processes, these results suggest that autoantibodies from LN patients may exert an important pathogenic effect by dephosphorylation of this protein in podocytes. Source

Lopez-Pedrera Ch.,University of Cordoba, Spain | Aguirre M.A.,University of Cordoba, Spain | Ruiz-Limon P.,University of Cordoba, Spain | Perez-Sanchez C.,University of Cordoba, Spain | And 3 more authors.
International Immunopharmacology | Year: 2015

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). Thrombosis is the major manifestation in patients with aPLs, but the spectrum of symptoms and signs associated with aPLs has broadened considerably, and other manifestations, such as thrombocytopenia, non-thrombotic neurological syndromes, psychiatric manifestations, livedo reticularis, skin ulcers, hemolytic anemia, pulmonary hypertension, cardiac valve abnormality, and atherosclerosis, have also been related to the presence of those 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. The currently accepted first-line treatment for obstetric APS (OAPS) is low-dose aspirin plus prophylactic unfractionated or low-molecular-weight heparin (LMWH). However, in approximately 20% of OAPS cases, the final endpoint, i.e. a live birth, cannot be achieved. Based on all the data obtained in different research studies, new potential therapeutic approaches have been proposed, including the use of new oral anticoagulants, statins, hydroxychloroquine, coenzyme Q10, B-cell depletion, platelet and TF inhibitors, peptide therapy or complement inhibition among others. Current best practice in use of these treatments is discussed. © 2015 Elsevier B.V. Source

Mehdi A.A.,American University of Beirut | Uthman I.,American University of Beirut | Khamashta M.,Lupus Research Unit
European Journal of Clinical Investigation | Year: 2010

Background Antiphospholipid syndrome (APS) is a systemic autoimmune vascular disease characterized by recurrent thrombotic episodes and/or obstetric complications. Management of this disease has been restricted mainly to anticoagulation; however, in recent years, significant advancement has been made in elucidating the pathophysiology of the disease including antiphospholipid antibody (aPL)-induced activation of the platelets, endothelial cells, monocytes, complement and coagulation cascade. Stemming from these advances, potential targeted therapeutic approaches have been proposed. Materials and methods We utilized a computer-assisted search of the literature (MEDLINE, National Library of Medicine, Bethesda, MD, USA) up until September 2009 using the keywords: antiphospholipid syndrome, antiphospholipid antibodies, anticardiolipin antibodies, lupus anticoagulant, anti beta-2 glycoprotein antibodies, complement system, tissue factor, p38 mitogen-activated protein kinase (p38 MAPK), nuclear factor kappa B, toll-like receptors, annexin, Rituximab, statins and tumour necrosis factor. Results Several study groups have separately demonstrated the importance of inflammatory mediators in the pathogenesis of APS. It was also established that tissue factor, MAPK, nuclear factors kappa B, and the complement system are integral to the disease process. Toll-like receptors and annexin have as well been associated with the disease pathophysiology. Some study groups proposed new targeted therapeutic strategies some of which have shown promising results in preclinical studies. These include Rituximab, complement inhibition, anti-cytokine therapy, p38 MAPK inhibitors, nuclear factor inhibitors and tissue factor inhibitors. Conclusion As more insight is being gained into the pathophysiology of APS, newer therapeutic strategies are being proposed that might lead to safer and more efficacious treatment modalities in the future. © 2010 Stichting European Society for Clinical Investigation Journal Foundation. Source

Yee C.-S.,University of Birmingham | Cresswell L.,MRC Biostatistics Unit | Farewell V.,MRC Biostatistics Unit | Rahman A.,University College London | And 12 more authors.
Rheumatology | Year: 2010

Objective. To develop an additive numerical scoring scheme for the BILAG-2004 index. Methods. SLE patients were recruited into this multi-centre cross-sectional study. At every assessment, data were collected on disease activity and therapy. Logistic regression was used to model an increase in therapy, as an indicator of active disease, by the BILAG-2004 index score in the nine systems. As both indicate inactivity, scores of D and E were set to 0 and used as the baseline in the fitted model. The models were used to determine the numerical values for Grades A-C. Different scoring schemes were compared. Results. There were 1510 assessments from 369 SLE patients. The coding schemes suggested for the Classic BILAG index (A = 12, B= 5, C= 1, D/E = 0 and A = 9, B= 3, C= 1, D/E = 0) did not fit the data well. A coding scheme (A = 12, B= 8, C= 1 and D/E = 0) was recommended, based on analysis results and consistency with the numerical coding scheme of the Classic BILAG index. Conclusion. A reasonable additive numerical scoring scheme based on treatment decision for the BILAG-2004 index is A = 12, B= 8, C= 1, D= 0 and E = 0. © The Author(s) 2010. Published by Oxford University Press on behalf of The British Society for Rheumatology. All rights reserved. Source

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