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Personalized medicine in systemic lupus erythematosus

Yovana Pacheco, Julián Barahona-Correa, Diana M Monsalve, Yeny Acosta-Ampudia, Manuel Rojas, Yhojan Rodríguez, Juliana Saavedra, Mónica Rodríguez-Jiménez, Rubén D Mantilla, Carolina Ramírez-Santana, Nicolás Molano-González, Juan-Manuel Anaya
BACKGROUND: Evidence supports the existence of different subphenotypes in systemic lupus erythematosus (SLE) and the pivotal role of cytokines and autoantibodies, which interact in a highly complex network. Thus, understanding how these complex nonlinear processes are connected and observed in real-life settings is a major challenge. Cluster approaches may assist in the identification of these subphenotypes, which represent such a phenomenon, and may contribute to the development of personalized medicine...
November 25, 2017: Journal of Translational Medicine
Cong Bi, Ryan Matsuda, Chenhua Zhang, Zitha Isingizwe, William Clarke, David S Hage
A method that combined on-line immunoextraction with high-performance affinity chromatography was developed to examine the binding of drugs with α1-acid glycoprotein (AGP). Affinity microcolumns containing immobilized polyclonal anti-AGP antibodies were developed that had a capture efficiency of up to 98.4% for AGP and a binding capacity of 0.72nmol AGP when using a 20mm×2.1mm i.d. microcolumn. These microcolumns were employed in various formats to examine the binding of drugs to normal AGP and AGP that had been adsorbed from serum samples for patients with systemic lupus erythematosus (SLE)...
October 13, 2017: Journal of Chromatography. A
Silvia Sirotti, Elena Generali, Angela Ceribelli, Natasa Isailovic, Maria De Santis, Carlo Selmi
The sequencing of the human genome is now well recognized as the starting point of personalized medicine. Nonetheless, everyone is unique and can develop different phenotypes of the same disease, despite identical genotypes, as well illustrated by discordant monozygotic twins. To recognize these differences, one of the easiest and most familiar examples of biomarkers capable of identifying and predicting the outcome of patients is represented by serum autoantibodies. In this review, we will describe the concept of personalized medicine and discuss the predictive, prognostic and preventive role of antinuclear antibodies (ANA), anti-citrullinated peptide antibodies (ACPA), rare autoantibodies and anti-drug antibodies (ADA), to evaluate how these can help to identify different disease immune phenotypes and to choose the best option for treating and monitoring rheumatic patients in everyday practice...
December 2017: Auto- Immunity Highlights
Alexandra Audemard-Verger, Elizabeth Comby, Clément Nathou, Audrey Sultan, Mathieu Frémont, Aurélie Baldolli, Louis Simon Trumier, Vincent Marzloff, Brigitte Le Mauff, Jennifer Manuzak, Sonia Dollfus, Boris Bienvenu
On the basis that diagnosis of neuropsychiatric systemic lupus erythematosus (NPSLE) is sometimes difficult and systemic lupus erythematosus (SLE) can present with isolated psychiatric symptoms, we initiated a survey in a psychiatric department to screen for NPSLE in young female inpatients.We prospectively studied consecutive young female patients referred to the department of psychiatry. Antinuclear antibodies (ANA), anti-deoxyribonucleic acid (DNA), and antiextractable soluble nuclear antigens (ENA) in the serum of patients were screened...
November 2016: Medicine (Baltimore)
Cindy Flower, Ian Hambleton, Mike Campbell
BACKGROUND: Medication adherence in systemic lupus erythematosus (SLE) reduces disease activity and the risk of flares. OBJECTIVES: We evaluated adherence in women with SLE who exhibit high morbidity and mortality. We evaluated demographic data and 2 conventional adherence predictors: self-efficacy and health literacy, along with 2 potential neuropsychiatric SLE complications: cognitive dysfunction and depression. METHODS: One hundred six women randomly selected from the Barbados National Lupus Registry completed the Self-efficacy for Appropriate Medication Use Scale, Rapid Estimate of Adult Literacy in Medicine-Short Form, Cognitive Symptom Inventory, Beck Depression Inventory II, and Morisky's Medication Adherence Questionnaire (MAQ)...
December 2016: Journal of Clinical Rheumatology: Practical Reports on Rheumatic & Musculoskeletal Diseases
Yi Zhan, Yu Guo, Qianjin Lu
Great progress has been made in the last decades in understanding the complex immune dysregulation in systemic lupus erythematosus (SLE), yet the efforts to pursue an effective treatment of SLE proved to be futile. The pathoetiology of SLE involves extremely complicated and multifactorial interaction among various genetic and epigenetic factors. Multiple gene loci predispose to disease susceptibility, and the interaction with epigenetic modifications mediated through sex, hormones, and the hypothalamo-pituitary-adrenal axis complicates susceptibility and manifestations of this disease...
2016: Cytogenetic and Genome Research
Andrea Doria, M Eric Gershwin, Carlo Selmi
The significant decrease in mortality rates worldwide, the increased proportion of patients achieving a durable remission, and the recent approval of a new drug after several decades are encouraging advances in the tangled history of systemic lupus erythematosus (SLE). However, when data are observed more closely, the research findings on disease pathogenesis and targeted treatments have been quite misleading, as illustrated by the central role of B cells but the missed endpoints in rituximab clinical trials which are burdened by the wide variability of SLE manifestations or the ethnic determinants of disease severity...
November 2016: Journal of Autoimmunity
R Biesen, T Rose, B F Hoyer, T Alexander, F Hiepe
Systemic lupus erythematosus (SLE) can be a mysterious disease, presenting with extremely divergent clinical phenotypes. Already, biomarkers are very helpful tools for diagnosis, assessment and monitoring of disease activity, differential diagnosis of clinical manifestations, prediction of the disease course and stratified therapy, and they hold the key to personalized medicine in SLE. We summarize the clinical information that can only be supplied by autoantibodies, complement components and interferon biomarkers in this diverse disease...
July 2016: Lupus
Hans-Joachim Anders, Marc Weidenbusch, Brad Rovin
Lupus nephritis (LN) remains a kidney disease with significant unmet medical needs despite extensive clinical and translational research over the past decade. These include the need to (i) predict the individual risk for LN in a patient with systemic lupus erythematosus, (ii) identify the best therapeutic option for an individual patient, (iii) distinguish chronic kidney damage from active immunologic kidney injury, (iv) develop efficient treatments with acceptable or no side effects and improve the design of randomized clinical trials so that effective drugs demonstrate efficacy...
October 2015: Clinical Kidney Journal
Shruti Sharma, Zhongbo Jin, Elizabeth Rosenzweig, Swapna Rao, Kichul Ko, Timothy B Niewold
Systemic lupus erythematosus (SLE) is a complex autoimmune disease of uncertain etiology. Patients from different ancestral backgrounds demonstrate differences in clinical manifestations and autoantibody profiles. We examined genome-wide transcriptional patterns in major immune cell subsets across different ancestral backgrounds. Peripheral blood was collected from African-American (AA) and European-American (EA) SLE patients and controls. CD4 T-cells, CD8 T-cells, monocytes, and B cells were purified by flow sorting, and each cell subset from each subject was run on a genome-wide expression array...
June 2015: Journal of Autoimmunity
Peter D Burbelo, Evan E Lebovitz, Abner L Notkins
Antibody profiles have the potential to revolutionize personalized medicine by providing important information related to autoimmunity against self-proteins and exposure to infectious agents. One immunoassay technology, luciferase immunoprecipitation systems (LIPS), harnesses light-emitting recombinant proteins to generate robust, high-quality antibody data often spanning a large dynamic range of detection. Here, we describe the general format of LIPS and discuss studies using the technology to measure autoantibodies in several human autoimmune diseases including type 1 diabetes, Sjögren's syndrome, systemic lupus erythematosus, and immunodeficiencies secondary to anticytokine autoantibodies...
February 2015: Translational Research: the Journal of Laboratory and Clinical Medicine
Elizabeth Price, Elizabeth Walker
Systemic lupus erythematosus (lupus) is a complex condition characterised by wide ranging symptoms that are sometimes transient in nature. This makes recognising and diagnosing lupus particularly challenging for both patients and practitioners. The diagnostic process in this condition is a complex interplay between the boundaries of knowledge and power, control, integrity and legitimacy, which are (re)constructed and (re)negotiated between contemporary medicine, the patient and practitioner. Utilising data generated through a qualitative research design, this article illustrates some of the challenges lupus presents in the clinical encounter...
May 2014: Health (London)
Jonas F Ludvigsson, Alberto Rubio-Tapia, Vaidehi Chowdhary, Joseph A Murray, Julia F Simard
OBJECTIVE: To investigate a possible association between celiac disease (CD) and systemic lupus erythematosus (SLE). Case series have indicated a possible association, but population-based studies are lacking. METHODS: We compared the risk of SLE in 29,048 individuals with biopsy-verified CD (villous atrophy, Marsh 3) from Sweden's 28 pathology departments with that in 144,352 matched individuals from the general population identified through the Swedish Total Population Register...
October 2012: Journal of Rheumatology
Fabien B Vincent, Eric F Morand, Fabienne Mackay
Recently, the B cell has emerged as a cornerstone of systemic lupus erythematosus (SLE) pathogenesis. This has been highlighted by studies of the cytokine B-cell-activating factor of the tumour necrosis factor (TNF) family (BAFF), a crucial factor regulating B-cell maturation, survival and function. Overexpression of BAFF in mice leads to the development of an SLE-like disease, independent of T cells but instead relying on innate immunity mechanisms. Moreover, BAFF has been shown to be elevated in the serum of patients suffering from autoimmune conditions, especially SLE, and may correlate with disease activity...
March 2012: Immunology and Cell Biology
N Agmon-Levin, M Mosca, M Petri, Y Shoenfeld
Systemic lupus erythematosus (SLE) characterizes by a variety of clinical manifestations and the presence of a wide profile of autoantibodies. This clinical and serological heterogeneity raised the question: is SLE a single disease with varied phenotypes, or a similar phenotype shared by different diseases with diverse pathogenic mechanisms? Herein we debate the clinical, genetic, hormonal and serological differences typically observed in SLE on the one hand, and the numerous similarities between subtypes of this disease on the other...
June 2012: Autoimmunity Reviews
Lesley Davila, Prabha Ranganathan
DMARDs not only improve the joint pain and swelling associated with rheumatoid arthritis (RA), but also slow down the joint damage associated with the disease. The efficacy of biologic therapies, introduced in the past decade for the treatment of RA, has been unequivocally established. Similarly, in addition to traditional drugs such as hydroxychloroquine, new biologic agents such as rituximab have been introduced for systemic lupus erythematosus in recent years. However, considerable variability occurs in the responses of patients to these therapies...
September 2011: Nature Reviews. Rheumatology
Benjamin Rhodes, Timothy J Vyse
Staggering advances have been made in our understanding of the genetic basis of human systemic lupus erythematosus (SLE), but has this been sufficient to fulfill early predictions that we could use genetics to provide personalized healthcare? Our current understanding of the genetic etiology of SLE indicates a strong underlying genetic predisposition, mediated by multiple gene variants. Compared with other complex genetic diseases, the disease risk imparted by many of these variants is strong. We argue that, for SLE, this particular combination of genetic effects means that the personalized prediction of disease onset or manifestation is certainly a realistic possibility, although further large-scale genetic studies will be required before this becomes a reality...
June 2010: Nature Reviews. Rheumatology
Mei-sheng Lai, Rui-qiang Fan
OBJECTIVE: To investigate the application of surface-enhanced laser desorption ionization time-of-flight mass spectrometry (SELDI) protein chip in diagnosis and Chinese medicie syndrome type researching of systemic lupus erythematosus (SLE). METHODS: Eighteen female SLE patients of mild/moderate degree with yin-deficiency caused internal heat syndrome (YDHS) were enrolled in the treatment group, and 15 women healthy volunteers was set up as the control group. Using SELDI method, the pre-, mid- and post-treatment peripheral blood mononuclear cell (PBMC) protein fingerprint of them was created respectively, which was then managed to screen out the markers by using ZUCI-PDAS package for establishing a diagnosis model...
January 2010: Chinese Journal of Integrated Traditional and Western Medicine
Luis E C Andrade
Human beings have taken successive approaches for the understanding and management of diseases. Initially brewed in supernatural concepts and mystical procedures, a vigorous scientific approach has emerged on the grounds of fundamental disciplines such as anatomy, microbiology, biochemistry, physiology, immunology, pathology, and pharmacology. The resulting integrated knowledge contributed to the current classification of diseases and the way Medicine is carried out today. Despite considerable progress, this approach is rather insufficient when it comes to systemic inflammatory conditions, such as systemic lupus erythematosus, that covers clinical conditions ranging from mild pauci-symptomatic diseases to rapidly fatal conditions...
September 2009: Anais da Academia Brasileira de Ciências
Eunice K Tan, George W M Millington, Nick J Levell
Classical acupuncture focuses primarily on treating the person, and secondarily treating the illness. The "symptoms" are regarded as "branch" expressions of a "root" (constitutional) imbalance. Different root imbalances can produce the same symptoms. Five patients with eczema, for example, may reveal five distinct root imbalances and would all be treated very differently. Because acupuncture treats the whole person, it has something to offer almost every condition. In many cases, acupuncture aims to bring about a complete cure; in others, it aims to manage the problem...
June 2009: International Journal of Dermatology
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