Access: Lupus Research -- Lupus Biomarkers
Research Summaries from 2012
Genetics of Lupus-Related Phenotypes
Genetic factors play a significant role in the susceptibility to developing lupus, but the relationship of genetic risk factors to lupus-related phenotypes (such as the presence or absence of specific autoantibodies) has remained largely unexplored. This study utilized both genetic data from lupus patients and data from public genetic databases to relate genetic lupus susceptibility to specific lupus-related phenotypes in European and African-American lupus patients. The results indicate that distinct sets of autoantibodies are associated with specific genetic risk variants in European and African-American lupus patients. These findings highlight that lupus can manifest in unique ways in people of different ethnic origins and that this can be at least partially related to genetic factors.
C-Reactive Protein as a Lupus Biomarker
C-reactive protein (CRP) has been studied as a lupus biomarker, but its exact role in lupus is yet to be elucidated. Most studies of CRP in lupus were unable to detect levels below a certain threshold, which may have limited the accuracy of the results. This study examines the role of CRP with the use of more sensitive methods that can detect very low levels of CRP (high sensitivity C-reactive protein, or hsCRP). The results of this study indicate that hsCRP is detectable in 77% of patients with clinically active lupus. In addition, hsCRP levels correlate with specific facets of lupus disease activity and with a number of factors related to increased cardiovascular disease risk.
Biomarkers-Driven Assessment of Lupus Progression
Lupus can be difficult to diagnose because the initial symptoms can often include common signs or symptoms of non-lupus origin. To help identify biomarkers of early lupus, the researchers aimed to establish a relationship between levels of specific autoantibodies and the evolution of clinical signs of lupus over time. The following were identified as significant risk factors for lupus progression: female gender, age less than 40 years, high baseline positivity for anti-nuclear antibodies, and increased IgG autoreactivity. These results are important and insightful, but need to be validated before being applied in the clinical setting.
Lupus-Related Changes in Energy Metabolism
People with lupus may experience chronic fatigue, the exact causes of which are yet to be fully understood. There are a number of different energy-producing metabolic processes that may be affected in people with lupus, but not much research has been done in this area. The results indicate lupus-related reductions in levels of metabolic markers crucial for energy production, as well as significant reductions in specific antioxidants. The relationship between these changes and some specific lupus drug therapies is discussed, as is possible dietary supplementation.
Seasonal Influences on Lupus Flares
Low levels of vitamin D in the blood are associated with increased lupus disease activity. The degree to which levels of vitamin D fluctuate during lupus flares, especially in different racial/ethnic groups, is not well-known. This study examined the relationship between fluctuating levels of vitamin D during different seasons, characterized by differing amounts of light exposure, while patients experienced lupus flares. The results of this study illustrate seasonal influences on lupus flares, which fluctuated with vitamin D levels uniquely in non-African-American but not in African-American lupus patients.
Combinations of Biomarkers Indicate Lupus Nephritis Pathology
Lupus nephritis, or lupus-related inflammation of the kidney, is one of the most common and potentially problematic aspects of systemic lupus erythematosus. Currently, a definitive diagnosis of lupus nephritis can only be made by a kidney biopsy, which involves removal of a small piece of kidney tissue for study. This procedure is invasive and, in some cases, the kidney may already be in a relatively advanced disease state at the time of the biopsy. The use of lupus biomarkers, such as those present in the blood or urine, to help predict and/or manage lupus nephritis over time could be very useful. The results of this study highlight the potential feasibility of using lupus biomarkers to differentiate between acute and chronic kidney disease activity-related changes.
Autoantibody Profiling in People with Lupus
Measurement and monitoring of autoantibody levels in people with lupus can be useful in diagnosis and disease monitoring and also have the potential to illustrate the efficacy of drug therapies being taken for lupus over time. There are a number of autoantibodies that are important in lupus, including antibodies to double-stranded DNA (anti-ds-DNA), anti-Smith antibodies, and others, which may have to be tested or measured separately (which can be time-consuming and/or costly). The development of a single test that can simultaneously measure several different autoantibodies important in lupus could be important and useful. The results indicate that a single test can indeed accomplish this and suggest that most lupus patients can be categorized into at least one of two groups that have distinct kinds of autoantibody profiles with unique susceptibilities to specific kinds of lupus manifestations.
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Research Summaries from 2011
Blood Test May Indicate Lupus Nephritis Activity
Inflammation of the kidneys, or lupus nephritis, is a relatively common and potentially severe manifestation of lupus. It can be difficult to accurately identify, however, without a kidney biopsy. The development of new kinds of tests that could help identify lupus nephritis disease and activity without the need for such an invasive procedure could be very useful. The researchers developed a new kind of blood test to help identify lupus nephritis disease and activity among a variety of patients with kidney disease (some with lupus and some without).
Biomarkers Predict Success of Lupus Nephritis Drug Therapy
Kidney involvement (nephritis) can be one of the more serious complications of lupus. Since lupus nephritis can be severe and the therapy can be toxic, it is important to be able to predict which patients would most benefit from long-term treatment. It would be particularly useful if specific factors could provide some advanced predictions about whether or not there would be successful responses to treatments for lupus nephritis. The researchers hoped to identify factors that might be seen after 8 weeks of treatment for nephritis that might predict whether or not the treatment would be successful after 24 weeks.
MicroRNAs Common to Three Lupus Mouse Models
MicroRNAs are small pieces of genetic material. Specific blueprints in the DNA can be “turned off” by these microRNAs so that some proteins won’t be made. The role of microRNAs in lupus has recently been studied in mouse models of lupus. If common sets of microRNAs could be identified in different mouse models of lupus with different genetic backgrounds, then this would very likely increase their usefulness for the study of lupus in people. The researchers hoped to identify a set of microRNAs common to three different strains of mice that have been genetically modified in different ways to have lupus, making it more likely that something similar to these microRNAs might be found in substantial percentages of people.
Blood Test for Antibodies That Might be Associated with Risk for Lupus Brain Inflammation
A protein in the brain called NR2A is part of a system that is important for learning and memory. Lupus patients can make antibodies to NR2A and some, but not all, studies have suggested that there might be a relationship between these antibodies and lupus brain inflammation (also known as neuropsychiatric lupus or NPSLE). The researchers studied the relationship between anti-NR2A antibodies and different aspects of lupus, especially whether there might be a relationship between these antibodies and NPSLE in patients from Japan.
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Are MicroRNAs Novel Biomarkers for Lupus Nephritis?
People inherit DNA from their parents and it contains the blueprints for making all of the proteins in the body. RNA is the translating material which helps in the conversion of these blueprints into functioning proteins. MicroRNAs are small pieces of RNA that help to regulate the extent to which instructions for making specific proteins can be used for that purpose. Specific blueprints can be “turned off” by microRNAs so that some proteins won’t be made. The role of microRNAs in lupus has recently been studied. Specific microRNAs have been identified in lupus patients and in some patients who have kidney involvement (lupus nephritis). In this study, the researchers hoped to learn whether people with lupus kidney involvement from different races shared the same set of microRNAs.
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New Blood Tests May Improve the Tracking of Lupus Kidney Disease in Children
Current treatments for lupus nephritis in children are toxic and sometimes ineffective. New tests for proteins that might be abnormal in lupus nephritis could help make the diagnosis earlier (when treatments have a better chance to work more quickly) and might also point to new ways of treating the disease (possibly with fewer side effects). In this study, the researchers hoped to find new tests for lupus nephritis in children.
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Research Summaries from 2010
Proteins on Blood Cells More Accurately Predict Lupus Disease Activity
There are a number of ways that a doctor can monitor people to try to predict lupus flares. The measurement of complement proteins, C4 and C3, in blood samples is widely used in this way. Measurement of two proteins that split off from C4 and C3 (C4d and C3d) and may be increased in the blood during inflammation has also been found useful, although these tests are not widely available at this time. The researchers hoped to learn whether measurement of C3d and C4d would be a more accurate way to test for lupus disease activity when measured while attached to a red blood cell than when they are freely circulating in the blood.
Urine Protein Indicates Presence of Lupus Nephritis
Lupus nephritis (LN) means that the kidney is inflamed. Currently, most people who are suspected of having LN have to get a kidney biopsy, a procedure in which small pieces of the kidney are removed for study under a microscope. But what if the availability of urine tests for LN may mean that a kidney biopsy one day may not be necessary to accurately diagnose LN? This will be an advantage for people with lupus since a kidney biopsy is an invasive procedure, can sometimes have serious side effects, and is not a practical way to monitor LN disease activity over time.
Urine May Help Track Kidney Disease and Predict Treatment Success in People With Lupus
Lupus nephritis (LN) -- inflammation of the kidney -- can damage the kidney’s ability to remove waste from the body. Currently, the best way to diagnose kidney inflammation is with a biopsy, an invasive procedure that can sometimes have serious side effects. Researchers have been working to develop specific tests that can be done on urine samples. The results of this study showed that levels of mRNA for FOXP3 could potentially become a test that can be done on simple urine samples to help figure out what is going on in the kidney and to help predict responses to current treatments for people with lupus.
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Potential New Indicators of Lupus Being Studied in Children
Since the 1970s, researchers have known that lupus patients are at risk for hardening of the arteries (“atherosclerosis”). Some of this risk may be from the increased inflammation that lupus patients have in the bloodstream over many years, but some of it is from the same reasons that hold true for everybody: especially high blood pressure, high blood glucose (sugar), or low levels of "good cholesterol."
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Research Summaries from 2009
Urine Components May Indicate Severity of Lupus Nephritis
Lupus may involve inflammation of the kidney, called lupus nephritis, which can impair the kidney’s ability to remove waste from the body. Since normal kidney function is vital, lupus nephritis requires aggressive treatments. Currently, the best way to diagnose kidney inflammation is with a biopsy, which is an invasive procedure that can sometimes have serious side effects. If there were tests that could be done to help diagnose and evaluate lupus nephritis without a biopsy, this would be a major advance for patients.
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MicroRNA’s Role in Interferon’s Contribution to Inflammation
Interferons (IFNs) are proteins produced by immune cells when the immune system is activated. They send different instructions to cells depending on the needs of the immune response; this can lead to cells making certain inflammatory proteins. IFNs communicate with the cells by linking up with receptor proteins along the cell surface, the way a key fits into a lock. This action sends a signal into the cell that eventually either turns on or turns off the process we recognize as inflammation. There are a number of signals and switches along the communication pathways that control inflammation, leading to the production of interferons and the ways in which interferons communicate with inflammatory cells. A group of very small substances called micro-RNA (miRNA) are thought to help in the regulation of inflammation in several ways. One way may be by interfering in the process by which genes (the genetic blueprint for the body) are translated into actual proteins (the machinery of the body).
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Research Summaries from 2008
New Ways to Detect Lupus Nephritis?
Kidney disease is diagnosed through a series of laboratory tests, and usually confirmed through biopsy. Biopsy -- in which kidney tissue is removed via insertion of a needle through the person’s back and then examined under a microscope -- is the most accurate way to discover the amount of damage that has occurred from lupus disease activity. However this procedure, which typically takes place in a hospital, can be expensive, can have side effects, and would only be done after kidney disease is suspected. For these reasons, less invasive and less expensive ways to routinely measure inflammation in the kidneys and disease progression would be of great benefit.
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Are Increased Levels of Nitric Oxide a Sign of Kidney Damage in Lupus?
Lupus disease activity often occurs without any apparent signs or symptoms. This is especially true when lupus affects the kidneys, which is known as lupus nephritis. It is even possible for lupus to cause significant kidney damage even before a patient is diagnosed. Though there may be no visible symptoms, there are chemical changes occurring in the cells and tissues that can be measured. Therefore, a major emphasis among lupus researchers is to find ways to tell if simple laboratory tests can be used to detect otherwise silent lupus disease activity. A laboratory test that can be used in this way is called a biomarker. One potential biomarker that is being investigated is nitric oxide (chemical symbol, NO), since it is one of the chemicals involved in the body’s immune response.
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Research Summaries from 2007
New Tests for Detecting Lupus Kidney Disease?
If the kidneys are damaged, they can lose their ability to filter out waste products from the blood and serious health complications can occur. The researchers in this study wanted to know if the presence of specific antibodies in a patient’s blood could be linked to the more severe kinds of kidney disease, in particular anti-dsDNA and anti-nucleosome antibodies. After reviewing the findings, the researchers calculated that lupus patients with anti-nucleosome antibodies were seven times more likely to develop lupus nephritis, suggesting that these antibodies could help to identify individuals at risk for this serious complication of lupus.
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New Tests for Detecting Lupus Kidney Disease? #2
In several previous studies, which did not include people with lupus, it appeared that high levels of lipocalin-2 in the urine could be an early predictor of kidney damage. The researchers for this study wanted to find out if there was an association between urinary lipocalin-2 and lupus-related kidney disease. The researchers found significantly higher levels of lipocalin-2 in the urine of lupus patients with active kidney disease than in the urine of the other lupus patients or among the healthy controls.
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Particular immune molecules and NPSLE
Despite the fact that a significant percentage of lupus patients (estimates run from 14% to 75%) have signs of neurological involvement, doctors still don't have a single test that can definitely indicate when lupus is affecting the central nervous system (NPSLE). The researchers sought to determine if the presence of particular factors in the spinal fluid (CSF) of lupus patients are associated with NPSLE, which might help determine NPSLE diagnosis. The researchers found increased concentrations of several inflammatory proteins in the CSF of lupus patients during a flare of NPSLE including interleukin 6 (IL-6) and several other proteins.
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BLyS Isotope May Serve as Lupus Biomarker
The immune protein BLyS, which is important to the survival and stimulation of the white blood cells called B-cells, has been tested as a marker for lupus in the past with variable outcomes. One of the proteins involved in regulating whether and how much BLyS protein is made by white blood cells might hold more promise.
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Potential Biomarker Identified for Neonatal Lupus
Researchers in France, England, and the United States may have identified a potential blood test that can be used to predict complications of pregnancy among women who have lupus. Their research focused on tiny segments of proteins (called peptides) that interact with antibodies called anti-Ro, and their association with the birth complication called neonatal lupus.
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