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Target Identification in Lupus

 LETTER OF INTENT DUE DATE: JULY 10, 2014

APPLICATION DUE DATE: AUGUST 25, 2014

Dear Lupus Researchers,

The Alliance for Lupus Research (ALR) is pleased to announce that the applications for the ALR’s Target Identification in Lupus (TIL) grants are now available online.  You can access the program guidelines for this application cycle here. The guidelines and application are also available though   the Altum proposalCENTRAL website at https://proposalcentral.altum.com.

Funding for the TIL award will be made for up to $200,000 per year (for a maximum of three years - total amount up to $600,000) including indirect costs. Funding for the third year is based on the successful submission of a non competitive progress report. The award amount will determined by the ALR’s Board of Directors based on the results of the peer review process including recommendations from the ALR’s Scientific Advisory Board.  Detailed guidelines for application and submission are available on the websites listed above. 

Deadlines associated with this grant program are as follows:

  •  Letter of Intent:           Due to ALR by July 10, 2014

Note : A non-binding letter of intent must be submitted by the investigator in advance of an invitation to apply for a grant. The letter must include a summary of the general theme and the potential future clinical ramification of the project future should it be successful.  Submission of the LOI does not commit the investigator to submitting an application; however it is required to be submitted in order to have access to the full application. The main purpose of this letter is to assist the ALR’ s Scientific Advisory Board in determining whether the proposed subject matter of the proposal falls within the ALR’s particular research goals during the upcoming funding year. 

  •  Grant Applications:   Due to ALR by August 25, 2014

The ALR funds research that will accelerate the development of new treatments for lupus.  As such, grant proposals should be innovative in direction and utilize state-of-the-art techniques.  Fundamental studies in genetics, immunology, cell biology and molecular biology to identify and characterize molecular systems must be oriented towards the development of drugs that would prevent and/or ameliorate clinical signs and symptoms of lupus. The ALR particularly welcomes applications proposing research that will apply knowledge gained in other disease areas (e.g., cancer, metabolic diseases) to mechanisms relevant to lupus.

Individuals with doctoral degrees (MD, PhD or equivalent) are eligible to apply.   Scientific independence as evidenced by direction of a research program, a publication record, or other experience that establishes scientific leadership is necessary to apply. The ALR does not impose geographic restrictions on its applicants, and investigators working anywhere in the world are eligible and encouraged to apply.  The ALR is willing to appropriately support research in industry or collaborations between academia and industry.

If you have any questions or require any additional information regarding the application process, please contact the ALR’s Research Administration department at 1-212-218-2840, 1-800-867-1743 or by e-mail at research.admin@lupusresearch.org.

Clinical Trials Request for Posting

Corporations, CRO’s and Investigators if you have clinical trials that you would like the ALR to post information on please click here for more information.

Below you will find links to some Clinical Trials that are looking For Researchers, Patients and to share data.

These trials are in no way affiliated with the ALR and are for informational Purposes only.

Embrace (Efficacy of Belimumab in Lupus Subjects of Black Race)

  • A phase 3/4, Multi-Center, Randomized, Double-Blind, Placebo-Controlled, 52 Week Study to Evaluate the Efficacy and Safety of Belimumab in Adult Subjects of Black Race with Systemic Lupus Erythematosus.

Bliss- SC Belimumab International SLE Study – Subcutaneous

  • A Phase 3, Multi-Center, Randomized, Double-Blind, Placebo-Controlled, 52-Week Study to Evaluate the Efficacy and Safety of Belimumab (HGS1006) Administered Subcutaneously to Subjects with Systemic Lupus Erythematosis (SLE).

Belimumab (Benlysta) Pregnancy Registry - Prospective Cohort Study of Pregnancy Outcomes following Belimumab Exposure

  • The Belimumab Pregnancy Registry is a global, observational cohort study. It will collect prospective pregnancy outcome data on a voluntary basis in women with systemic lupus erythematosus (SLE) who have received belimumab (Benlysta). Infant outcomes from babies born to mothers in this Registry will also be evaluated. Registry data will add to the current clinical experience with belimumab and complement reproductive data from animal toxicology studies. This Registry is sponsored by GlaxoSmithKline (GSK) and managed by Pharmaceutical Product Development (PPD), Inc

Bliss – LN Belimumab International Lupus Nephritis Study

  • A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Belimumab plus Standard of Care Induction and Maintenance Therapy for Active Lupus Nephritis.

PLUTO – (Pediatric Lupus Trial Of belimumab)

  • A Multi-Center, Randomized Parallel Group, Placebo-Controlled Double-Blind trial to Evaluate the Safety, Efficacy, and Pharmacokinetics of Belimumab, A Human Monoclonal Anti-BLyS Antibody, Plus Standard Therapy in Pediatric Patients with SLE.

SABLE SLE Registry

  • A 5-Year Prospective Observational Registry to Assess Adverse Events of Interest and Effectiveness in Adults with Active, Autoantibody-Positive SLE Treated with or without BENLYSTA (belimumab) (SABLE).

BASE (Belimumab Assessment of Safety in SLE)

  • A Randomized, Double-Blind, Placebo-Controlled 52 Week Study to Assess Adverse Events of Special Interest in Adults with Active, Autoantibody-Positive Systemic Lupus Erythematosus Receiving Belimumab.

Mary K. (Peggy) Crow, M.D. (Chair)

Mary K. Crow, M.D., is the Benjamin M. Rosen Professor and Senior Scientist at Hospital for Special Surgery in New York and Professor of Medicine and Immunology at Weill Medical College of Cornell University. At Hospital for Special Surgery, Dr. Crow is Director of Rheumatology Research and Associate Chief of Rheumatology. In addition, she serves as Director of the Autoimmunity and Inflammation Research Program and as Co-Director of the Mary Kirkland Center for Lupus Research.

Dr. Crow earned an M.D. from Cornell University Medical College and completed an internship and internal medicine residency at New York Hospital in Manhattan. Her rheumatology clinical fellowship training was performed at Hospital for Special Surgery. She also served as a post-doctoral research fellow at Rockefeller University, where she was mentored by Dr. Henry Kunkel, a renowned immunologist who made significant contributions to the understanding of the mechanisms responsible for autoimmune diseases, including rheumatoid arthritis and systemic lupus erythematosus.

Dr. Crow served as President of the American College of Rheumatology (2005-2006) and is very active in the rheumatology research community. Her own research has focused on the induction and regulation of human autoimmunity. She was among the first to characterize the functional properties of human dendritic cells and has studied self-reactive T cells in the prototype systemic autoimmune diseases, systemic lupus erythematous and rheumatoid arthritis. She continues to investigate the underlying triggers of autoimmune disease and the cellular and cytokine mediators of uncontrolled immune system activation in those disorders. She has published more than seventy scientific papers and has received research grant support from the NIH, the Arthritis Foundation, the Alliance for Lupus Research, the Lupus Research Institute, and the Mary Kirkland Center for Lupus Research. She was named an “Arthritis Hero” by the Arthritis Foundation in 2001.


Anthony J. Coyle, Ph.D.

Anthony “Tony” Coyle is Vice President and Chief Scientific Officer of the Centers for Therapeutic Innovation (CTI). CTI was established in August 2010 as a new model to drive innovation in BioTherapeutics R & D. Tony is responsible for the CTI sites, which currently include CTI – New York City, CTI- Boston and CTI-California. Tony is supported by his leadership team, which will include the site heads of each CTI, his operations team, project management, clinical and Precision Medicine heads.

Tony brings an extensive knowledge of the full development process to Pfizer. As a former Vice President and Global Head of Respiratory, Inflammation, and Autoimmunity Research at Medimmune Biologics, a Division of AstraZeneca, Tony has succeeded in advancing a biologic portfolio from discovery to Phase Two in the areas of Lupus, Asthma and COPD.

Prior to Medimmune, Tony was Director of Research and Biology at Millennium Pharmaceuticals, where he led a group responsible for the identification of novel target genes as well as for late stage lead optimization and delivery of both small molecule and biologic development candidates.

Tony has been Associate Professor in the Department of Pathology and Experimental Therapeutics at McMaster University in Ontario since 1992, and has authored more than 180 manuscripts. He holds a B.Sc. Honours and a Ph.D. from Kings College, University of London.


Saeed Fatenejad M.D.


Richard Furie, M.D.

Dr. Richard Furie, Chief of the Division of Rheumatology and Allergy-Clinical Immunology at the North Shore LIJ Health System, is a rheumatologist whose activities for the last several decades have focused on patient care, physician education, and clinical research in the area of anti-rheumatic drug development. He directs The Program in Novel Therapeutics, the Health System’s clinical research program in musculoskeletal disease. He also directs the Hospital’s SLE and Autoimmune Disease Treatment Center, which has become internationally recognized for its role in the development of new therapies for SLE. Regarded as one the senior rheumatologists in the New York metropolitan area, he has been on the Boards of Directors of the local chapters of the Arthritis Foundation and the Lupus Alliance of America and is a member of the Medical-Scientific Advisory Council of the Lupus Foundation of America as well as its Lupus News editorial board. He also is on the Medical and Scientific Advisory Board of the SLE Foundation as well as the Alliance for Lupus Research Scientific Advisory Board. Dr. Furie has served on many committees of the American College of Rheumatology, and has recently been appointed to the College’s Board of Directors.


Peter E. Lipsky, M.D.

Dr. Peter E. Lipsky received his medical degree from the New York University School of Medicine and spent much of his career at the University of Texas Medical Center, initially as Instructor in Internal Medicine and later as Professor of Internal Medicine and Microbiology. Later appointments at the University of Texas Medical Center (1984-1999) included Director of the Harold C Simmons Arthritis Research Center, Co-Director of the Immunology Graduate Program at the Southwestern Graduate School of Biomedical Sciences, and Director of the Rheumatic Disease Division of the Department of Internal Medicine. Dr Lipsky was named the Harold C Simmons Professor in Arthritis Research in 1995, a position he held for 5 years.

Dr Lipsky's major research interests are B-cell biology, both in normal and autoimmune disease settings, and the generation of the immunoglobulin repertoire, and has authored over 500 articles. He serves on numerous journal editorial boards, and is the Co-Editor of Arthritis Research and Therapy and the Editor in Chief for Nature Clinical Practice Rheumatology. He has been awarded numerous prizes, including the Carol Nachman Prize in 2001, the Lee C. Howley Prize for Arthritis Research in 2002, the American College of Rheumatology's Distinguished Investigator Award in 2002, and the Japan Rheumatology Prize 2006.


Mike McCune, M.D., Ph.D.

Research in the McCune Lab has focused on the definition of pathogenic mechanisms of viral diseases, particularly HIV disease. This focus has spanned a range of fields, from understanding critical structural determinants of infectivity, to devising a small animal model (the SCID-hu Thy/Liv mouse) to study HIV pathogenesis and to prioritize antiretroviral compounds against HIV, to studying mechanisms of T cell depletion and repletion in vivo. Throughout this body of work, he has engaged in hypothesis-driven, patient-oriented research that has involved collaborative teams of basic scientists, translational researchers, and clinicians. Most recently, he has devoted all of his attention to understanding the correlates of protective immunity against HIV, with the specific intent to work with others to eradicate HIV. This change of focus has now been materialized at UCSF by the creation of the Division of Experimental Medicine, of which Dr. McCune is the Chief. From 2005-2008, he served as the PI and Director of the Clinical and Translational Science Institute at UCSF, an organization whose mission is to enhance and to facilitate the process by which better therapies can be brought from the lab bench to the community more quickly. In this capacity, he also served as the Senior Associate Dean of Clinical and Translational Research in the Schools of Dentistry, Medicine, Nursing, and Pharmacy at UCSF.

In the Division of Experimental Medicine, he has established a multidisciplinary, collaborative environment for the analysis of the human immunology of chronic infectious diseases of medical importance, including those caused by HIV, TB, malaria, and helminthic worms. The underlying hypothesis of the Division is that each of these agents has established patterns of interaction with the host which, in most cases, do not lead to overt disease; that these patterns are likely to embrace protective immune responses with mechanistic overlaps; and that elucidation of such common patterns of successful host-pathogen interaction may inform the development of interventions (e.g., vaccines and medicines) to successfully fight HIV.


Jane Salmon, M.D.

Dr. Jane Salmon is Professor of Medicine and Professor of Obstetrics and Gynecology at Weill Cornell Medical College and the Collette Kean Research Professor at Hospital for Special Surgery.

Dr. Salmon graduated magna cum laude from New York University and earned a medical degree in 1978 from the College of Physicians and Surgeons of Columbia University, where she was the first woman enrolled in their Medical Scientist Training Program. She completed training in internal medicine at The New York Hospital and in rheumatology at Hospital for Special Surgery, and has been an HSS faculty member since 1983. Dr. Salmon has served on the Board of Directors of the American College of Rheumatology and as Councilor of the Clinical Immunology Society. She has served on the NIH Advisory Boards for the North American Rheumatoid Arthritis Consortium and the Lupus Multiplex Registry and was co-editor of Arthritis and Rheumatism. At Hospital for Special Surgery, she is a co-Director of the Mary Kirkland Center for Lupus Research, Director of the SLE APS Center of Excellence, Director of the FOCIS Center of Excellence, and Director of the Lupus Registry and Repository.

Dr. Salmon’s research has focused on elucidating mechanisms of tissue injury in lupus and other autoimmune diseases. Her basic and clinical studies have expanded our understanding of pregnancy loss and organ damage in SLE and the determinants of disease outcome in lupus patients with nephritis, pregnancy, and cardiovascular disease.


George Tsokos, M.D.

Dr. Tsokos received his Medical Degree and a Doctorate in Sciences from the University of Athens. He trained in Internal Medicine at the University of Athens and Georgetown University/VA Medical Center in Washington DC and completed Immunology and Rheumatology Fellowships at the National Institutes of Health. Between 1987 and 2007 he was a member of the Uniformed Services/Walter Reed community where served in various positions including Vice Chair for Research in the Department of Medicine and Chief of the Department of Cell Injury. In 2007 he joined the Beth Israel Medical Center as Chief of Rheumatology and Harvard Medical School as Professor of Medicine.

He has served various leadership positions including President of the Clinical Immunology Society and as member or chair of multiple federal study sections and editorial boards of scientific journals. He has served (or serves) as Consulting Editor of the Journal of Clinical Investigation, Editor of Autoimmunity, Academic Editor of PLOS One and Editor-in-Chief of Clinical Immunology. He has been elected to the Association of American Physicians, Fellow of the American Association for the Advancement of Sciences and Master of the American College of Physicians.

Dr. Tsokos’ research focuses on the cellular and molecular pathogenesis of systemic lupus erythematosus (SLE). His laboratory has opened and led the field of molecular abnormalities on immune cells in patients with SLE. He has identified several molecular abnormalities, including aberrant expression of CD3 zeta chain, cAMP response element modulator, calcium-calmodulin kinase IV and protein phosphatase 2A and demonstrated that when their expression is corrected in cells obtained from patients with SLE with either gene transfer or small molecule drugs the effector cell function returns to normal levels. More recently he has constructed a series of novel mice to demonstrate in vivo the importance of the molecules expressed aberrantly in SLE T cells in the expression of autoimmunity and organ damage.

Dr. Tsokos has trained over 100 colleagues many of whom hold senior leadership positions and run independent laboratories and has published more than 450 articles. His research is funded by NIH and DoD grants.


2014 Alliance for Lupus Research Scientific Calendar

View Our special reports on the ACR and other Meetings

February 1, 2014 2012 Target Identification in Lupus (TIL) Grants Activated  
February 20, 2014 Lupus Insight Prize Application Due  
June 5, 2014 2014 TIL Grants Request for Application Distributed  
May 8-9, 2014 Investigators’ Collaborative Meeting  
May 8, 2014 Scientific Advisory Board Meeting  
June 25, 2014 Lupus Insight Prize Ceremony  
August 25, 2014 2014 TIL Grant Application Due  
November 2014 2014 TIL Peer Review Meeting  
December 2014 Scientific Advisory Board Meeting  

Scientific Meetings

Jan 25-31, 2014 Winter Rheumatology Symposium – Snowmass, Colorado
March 7-9, 2014 Third Inaugural Meeting of the Lupus Academy – Berlin, Germany
March 26-30, 2014 9th International Congress on Autoimmunity – Nice, France
March 31- April 4, 2014 16th Asia Pacific League of Associations for Rheumatology – Cebu City, Philippines
May 2-6, 2014 The American Association of Immunologists – IMMUNOLOGY 2014 – Pittsburg, Pennsylvania
June 11-14, 2014 EULAR 2014 Paris, France
June 25-28, 2014 Federation of Clinical Immunology Societies 2014 – Chicago, Illinois
July 1-4, 2014 Frontiers in Immunology Research International Conference – Florence, Italy
October 12-16, 2014 International Conference on Nervous System Autoimmunity – Goa, India
November 14-19, 2014 ACR/ARHP 77TH Annual Scientific Meeting – Boston, Massachusetts
March 12-14, 2015 CORA 2015: Controversies in Rheumatology & Autoimmunity – Sorrento, Italy - Happens every two years
August 21-26, 2016 International Congress of Immunology – Melbourne, Australia - Happens every three years

Special Reports

View Highlights from the ALR's 2013 American College of Rheumatology Annual Scientific Meeting

View highlights from the ALR's 2011 American College of Rheumatology Annual Scientific Meeting

View highlights from the ALR's 2010 American College of Rheumatology Annual Scientific Meeting

View the Lupus Congress 2010 Special Report

RS rearrangement frequency as a marker of receptor editing in lupus and type 1 diabetes - Eline T. Luning Prak

Continued antibody gene rearrangement, termed receptor editing, is an important mechanism of central B cell tolerance that may be defective in some autoimmune individuals. We describe a quantitative assay for recombining sequence (RS) rearrangement that we use to estimate levels of antibody light chain receptor editing in various B cell populations. RS rearrangement is a recombination of a noncoding gene segment in the  antibody light chain locus. RS rearrangement levels are highest in the most highly edited B cells, and are inappropriately low in autoimmune mouse models of systemic lupus erythematosus (SLE) and type 1 diabetes (T1D), including those without overt disease. Low RS rearrangement levels are also observed in human subjects with SLE or T1D.

...

Read the Full article here

Source: Alliance for Lupus Research
Funded Research

Role of tissue factor in a mouse model of thrombotic microangiopathy induced by antiphospholipid (aPL) antibodies - Guillermina Girardi

We developed a new animal model of TMA induced by antiphospholipid (aPL) antibodies, an invaluable tool to understand the molecular and cellular eventsthat determine glomerular endothelial injury. Using this model we found more than one mechanism/signaling pathway is involved in glomerular injury induced by aPL- antibodies. Both complement dependent and complement-independent pathways were identified that lead to glomerular endothelial cell damage and renal function impairment. We also found that C5a-C5aR interaction is a crucial step for the activation of the coagulation cascade and glomerular injury induced by complement activating antibodies. In addition, our studies demonstrated complement independent mechanisms in which reactivity with β2 glycoprotein I (β2GPI) plays an important role in aPL-induced glomerular damage and renal failure. Independently of the mechanism responsible for aPL-induced TMA, mice that express low levels of tissue factor (TF) were protected from glomerular injury.

...

Read the Full article here

Source: Alliance for Lupus Research
Funded Research

 

Neutrophil Gelatinase Associated Lipocalin As A Biomarker Of Disease Activity In Pediatric Lupus Nephritis - Hermine I. Brunner, MD MSc

To investigate neutrophil gelatinase associated lipocalin(NGAL) concentrations in relation to disease features and worsening of disease activity in pediatric SLE(pSLE), particularly with regard to lupus nephritis.

NGAL in plasma (PNGAL) and urine (UNGAL) were measured by ELISA in 85 participants with pSLE over time (132visits), healthy children (n=50), and children with juvenile idiopathic arthritis (JIA, n=30. pSLE disease features and results of standard laboratory testing were recorded. Disease activity was measured by the systemic lupus disease activity index (SLEDAI-2K).

NGAL in plasm and urine is elevated in pSLE compared to JIA or healthy controls. UNGAL and, to a lesser degree, PNGAL increased with worsening of global, but especially renal disease activity, and may represent novel biomarkers for pSLE. ...

Read the Full article here

Source: Alliance for Lupus Research
Funded Research

Maternal lupus and congenital cortical impairment - Bruce T. Volpe

Systemic lupus erythematosus (SLE) is an autoantibody (AAb)-mediated disease that preferentially affects women of childbearing age. Since the offspring of mothers with SLE exhibit a high frequency of learning disorders, we hypothesized that maternally transferred AAbs that bind DNA and the N-methyl-D-aspartate receptor (NMDAR) could play a pathogenic role during fetal brain development. Here we describe a maternal SLE murine model wherein pregnant dams harbored anti-DNA, anti-NMDAR AAbs throughout gestation. High titers of these AAbs in maternal circulation led to histopathological abnormalities in fetal brain and subsequent cognitive impairments in adult offspring. These data support a paradigm in which in utero exposure to neurotoxic AAbs causes abnormal brain development with long-term consequences. This paradigm may apply to multiple congenital neuropsychiatric disorders.

Studies demonstrate that children born to mothers with SLE display a high incidence of learning disorders compared to children born to healthy mothers1-5. In one study as many as 45% of the male and 8% of the female offspring of SLE mothers were affected, generally displaying dyslexia or difficulty with mathematical calculations1. The mechanisms for the learning disorder remain unknown, but prematurity, low birth weight, maternal disease activity, and medications during pregnancy have not emerged as significant causative factors. The striking observation that children born from SLE fathers do not exhibit learning disorders led us to ask whether maternally derived factors, antibodies (Abs) in particular, might alter fetal brain development in utero and result in long-term changes in cognitive function of the offspring.

...

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Source: Alliance for Lupus Research
Funded Research

IL-2 Treatment Enhances Expression of FOXP3 in Lupus but not Diabetic Subjects - Jane H. Buckner

A lack of IL-2 synthesis and responsiveness are clearly responsible for diminished CD4+CD25+FOXP3+ T cells (Treg) survival and function in mice, however, it is not fully understood how deficiencies in IL-2 synthesis, IL-2 receptor expression and IL-2 receptor function influence maintenance and induction of FOXP3 expression in human CD4+ T cells and whether these effects alter disease processes. To determine whether human Treg require IL-2 for survival and persistence we studied subjects with either lupus, a disease characterized by defects in IL-2 synthesis, or T1D, a disease associated with SNP’s in CD25 and PTPN2, a phosphates involved in IL-2 signal transduction.

...

Read the Full article here

Source: Alliance for Lupus Research
Funded Research

High density genotyping of STAT4 gene reveals multiple haplotypic associations with Systemic Lupus Erythematosus in different racial groups - Chaim O. Jacob MD, PhD

Objective: Systemic lupus erythematosus (SLE) is the prototypic systemic autoimmune disorder with complex etiology and a strong genetic component. Recently, gene products involved in the interferon pathway have been under intense investigation in SLE pathogenesis. STAT1 and STAT4 are transcription factors that play key roles in the interferon and Th1 signaling pathways, making them attractive candidates for SLE susceptibility.

Methods: Fifty-six single-nucleotide polymorphisms (SNPs) across STAT1 and STAT4 genes on chromosome 2 were genotyped using Illumina platform as a part of extensive association study in a large collection of 9923 lupus cases and controls from different racial groups. DNA from patients and controls was obtained from peripheral blood. Principal component analyses and population based case-control association analyses were performed and the p values, FDR q values and Odds ratios with 95% confidence intervals (95% CIs) were calculated.

Results: We observed strong genetic associations with SLE and multiple SNPs located within the STAT4 gene in different ethnicities (Fisher combined p= 7.02x10-25). In addition to strong confirmation of the association in the 3rd intronic region of this gene reported previously, we identified additional haplotypic association across STAT4 gene and in particular a common risk haplotype that is found in multiple racial groups. In contrast, only a relatively weak suggestive association was observed with STAT1, probably due to the proximity to STAT4.

...

Read the Full article here

Source: Alliance for Lupus Research
Funded Research

The Peroxisome Proliferator-Activated Receptor

Systemic lupus erythematosus (SLE)3 is a chronic autoimmune disease that affects primarily young women. The disease is highly heterogeneous in its clinical presentation which renders therapeutic interventions particularly challenging. A significant proportion of patients develop nephritis which typically requires the use of corticosteroids and cytotoxic agents (1). Although these agents have been used with varying success, they tend to be associated with significant side effects.

Importantly, SLE is associated with a striking increase in the risk of premature cardiovascular (CV) complications due to accelerated atherosclerosis (2), which significantly contributes to morbidity and mortality in this patient population (3). Although traditional risk factors may play a role in this increased propensity, they do not seem to fully account for this complication (4). As such, immune dysregulation characteristic of lupus may play a prominent role in the development of premature atherosclerosis. However, the exact etiology of increased CV risk in SLE remains unclear. A significant proportion of individuals with SLE have evidence of subclinical vascular disease which may precede atherosclerosis development.

...

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Source: Alliance for Lupus Research
Funded Research

The histone deacetylase inhibitor trichostatin A upregulates regulatory T cells and modulates autoimmunity in NZB/W F1 mice

We sought to determine if the histone deacetylase inhibitor (HDI), trichostatin A (TSA), would alter systemic lupus erythematosus (SLE) in NZB/W mice. Fourteen to sixteen-week-old female NZB/W F1 mice were given TSA (1.0mg/kg body weight (BW)) intraperitonealy (i.p.) daily, TSA (1.0mg/kg BW) i.p.+anti-CD25 (250mg/mouse) i.p. every third day, only anti-CD25 (250mg/mouse) i.p., DMSO or isotype IgG. Disease progression was assessed as they aged. Mice were sacrificed at 26 or 38 weeks of age, tissues collected and evaluated. At 36 weeks, TSA-treated animals had decreased anti-double stranded DNA (dsDNA) autoantibodies and decreased protein excretion compared to controls. Spleen size and the percentage of CD4+CD69+ cells were decreased, with an increase in CD4+CD25+ T cells in the TSA-treated mice. Real-time reverse transcription-polymerase chain reaction (RT-PCR) analysis of T cells showed a decrease in IL-6 production but an increase in TGF-beta1 and Foxp3 in the TSA-treated animals. Kidney analysis showed a decrease in IgG and C3 deposition, decrease in pathologic glomerular disease and renal MCP-1, MMP-9, and IL-6 mRNA expression. Anti-CD25-treated mice euthanized at 26 weeks of age showed decreased Foxp3+CD4+CD25+ T cells compared to TSA-treated mice. These data suggest TSA administration modulates lupus-like disease, in part, by increasing T regulatory cells.

Click to read full publication

Urinary Neutrophil Gelatinase-Associated Lipocalin as a Biomarker of Nephritis in Childhoo-Onset Systemic Lupus Erythematosus - Hermine I. Brunner, MD MSc

Renal involvement in systemic lupus erythematosus (SLE) is associated with poor prognosis.
 
Currently available renal biomrkers are relatively insensitive and nonspecific for diagnosing SLE nephritis. Previous research suggests that neutrophil gelatinase-associated lipocalin (NGAL)  is a high-quality renal biomarker of acute kidney injury, while its usefulness in SLE is unclear.

We undertook this study to determine the relationship between urinary NGAL excretion and SLE disease activity or damage, with a focus on nephritis.

...

Read the Full article here

Source: Alliance for Lupus Research
Funded Research

Type I Interferon Review in Systemic Lupus Erythematosus and Other Autoimmune Diseases - Virginia Pascual

Different genetic alterations may lead to type I interferon (IFN) overproduction inhuman systemic lupus erythematosus (SLE). The increased bioavailability of type I IFN contributes to peripheral tolerance breakdown through the activation of immature myeloid dendritic cells (mDCs). IFN-matured mDCs activate autoreactive T cells. These cells, together with plasmacytoid DCs, help expand autoreactive B cells. IFNmatured DCs also activate cytotoxic CD8+ T cells, possibly increasing apoptotic cell availability. The capture of apoptotic cells bymDCs and of nucleic acid-containing immune complexes by plasmacytoid DCs and B cells amplifies the autoimmune reaction leading to disease manifestations. Genetic alterations in lineages other than B cells might explain other autoimmune syndromes where type I IFNs appear to be involved.

...

Read the Full article here
Source: Alliance for Lupus Research
Funded Research


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