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VBCR - June 2015, Volume 4, No 3 - CCR Conference Highlights
Chase Doyle

In the rapidly evolving field of medicine, what may seem esoteric today could be standard of care tomorrow. Biomarkers, whether a simple blood test or a complicated imaging technology, inhabit this bleeding edge—a confounding space of limitation and potential, where better outcomes are only a single measurement away.

According to a presentation at the 2015 annual Congress of Clinical Rheumatology, lupus needs a biomarker—stat.

“Biomarkers are not esoteric,” said Susan Manzi, MD, MPH, co-director of the Allegheny Health Network’s Lupus Center of Excellence in Pittsburgh, and professor at Temple University School of Medicine in Philadelphia. “They provide a very practical application to patient care and decision making. I would love to have a test [for lupus] that provides a level of certainty in terms of susceptibility, diagnosis, disease activity, or prognosis and subsetting.”

While the concept of a biomarker is simple—a physical, cellular, biochemical, molecular, or genetic measurement that indicates a normal biological process, a pathogenic process, or some kind of pharmacologic response—the path to finding one in lupus has been anything but.

Easy to measure and very inexpensive, blood pressure and low-density lipoprotein (LDL) cholesterol are the greatest biomarkers in the cardiovascular world: both are indicative of pathologic conditions (hypertension and hyperlipidemia, respectively) and both can predict bad outcomes (cardiovascular events, stroke, etc).

“The holy grail in lupus is a blood pressure or LDL marker that can be that good at predicting outcomes of our diseases,” said Manzi.

Unfortunately, for a heterogeneous disease like lupus, even diagnosis requires multiple tests, and accuracy is seldom guaranteed. As Manzi explained, lupus is an outlier, the rare kind of illness that can be both under- and overdiagnosed, particularly among primary care physicians.

“Diagnostic accuracy was only 50% for nonrheumatologists,” she said, “and even rheumatologists only had 80% accuracy…Some people believe that we shouldn’t even call it a disease, we should call it a spectrum or a syndrome of multiple diseases within.”

The point being: it is not easy to determine whether someone has lupus or not, which leads to utilization of myriad medical resources and untold expense.

The identification of patients before disease would be ideal and will, perhaps, one day be possible, with the rapid pace of gene discovery from high-throughput sequencing technology.

“When you look at genome-wide scans,” said Manzi, “you can see certain loci much more commonly expressed in lupus than in controls…You can categorize [genes] by pathways that are relevant to lupus, whether it’s immune complex processing or signal transduction with interferon pathway, and this leads to more investigation into those pathways, not only understanding why you get lupus but also targeting therapies and developing for drug discovery.”

Beyond improving diagnostic accuracy, biomarkers that help identify what will happen to a patient, once he or she receives a diagnosis, will enable more effective treatment.

“We want to be able to monitor disease activity,” she said. “A biomarker that tells us, without subjectivity, when a patient is going to get sick or that can predict flares would be incredibly useful.”

According to Manzi, autoantibody status already plays a role in the diagnosis and clinical subsetting of lupus, but it is not sufficient to stand alone; other measures are needed. Cell-bound complement activation products could provide a portfolio of biomarkers for diagnosis, monitoring, and subsetting, and proinflammatory high-density lipoprotein (HDL) may represent a biomarker for cardiovascular disease in lupus. There is also imaging in the form of carotid ultrasound to aid in predicting cardiovascular disease in high-risk patients.

In the end, however, it could be a combination of all the above—and other, heretofore unknown indicators—that provide lupologists with the “grail” they desperately seek. Manzi imagines these biomarkers will likely require a panel of tests that can be compiled into indices.

“It’s going to be hard work,” she concluded, “but if we can identify people before they develop disease, intervene early, or better prognosticate so we can aggressively treat for any organ we think our patients are at risk for, it will definitely be worth it.”

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Last modified: June 29, 2015
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