Progentec Diagnostics, Inc. just launched a novel blood test to determine the likelihood that a patient with systemic lupus erythematosus (commonly known as both SLE and lupus) will experience an immunologic disease flare during the coming 12 weeks.
The aiSLE™ DX Flare Risk Index is a laboratory test that measures the blood-based biomarkers that are measurably altered before the onset of flare symptoms in lupus patients. Early research measured 52 soluble immune mediators, including cytokines and chemokines, in plasma before disease flares. Studies of patient samples have allowed that panel to be reduced to 11 biomarkers.
In the assay, a weighted algorithm assesses the measurements from the blood test and calculates a score for the risk of flares during the next 12 weeks. Patients with a positive index score are nearly five times more likely to experience a flare than a patient with a negative score.
This appears to be the first proactive test for lupus, and provides an objective measurement of lupus activity for America’s 1.5 million lupus patients. Because it predicts periods of increased disease activity, it is expected to notably improve quality of care by enabling intervention before the event.
Alternative methods to measure lupus disease activity, such as the SELENA-SLEDAI flare index and BILAG index, are based on a rheumatologist’s assessment of physical symptoms in addition to laboratory tests.
“The empirical data derived from (the aiSLE™ DX Flare Risk Index) potentially has tremendous value in helping devise the right treatment and care for lupus patients,” Chaim Putterman, M.D., professor of medicine and microbiology & immunology at the Albert Einstein College of Medicine, and a member of Progentec’s Scientific Advisory Board, said in a statement. Specifically, “Proactive treatment strategies based on the aiSLE™ DX Flare Risk Index result may help clinicians and patients reduce the negative impacts of lupus flares, which include organ damage, hospitalizations, and reductions in patient quality of life.”
Just as the signs and symptoms of lupus change over time, disease activity also fluctuates. Patients experience an average of 1.8 flares each year, which require the use of fast-acting therapeutics, such as corticosteroids.
Identifying biomarkers, therefore, held promise. Prior studies showed that altered Type II interferon precedes autoantibody accrual and elevated interferon activity. Thus, it was a biomarker for identifying people at risk for developing lupus years before they otherwise would be diagnosed. Other researchers, publishing in Clinical Rheumatology, determined that higher activation of the interferon-gamma signaling pathway in lupus patients was closely correlated to disease activity.
Importantly, a study by M.E. Munroe and colleagues at the Oklahoma Medical Research Foundation (OMRF) analyzed patients of African American as well as European ancestry.
“African American (AA) SLE patients have an increased prevalence of complications from disease flares and end-organ damage that leads to increased morbidity and early mortality,” according to a paper published in the Journal of Autoimmunity in 2017.
In that paper, Munroe and colleagues documented “significant alterations in 34 soluble mediators at baseline, with increased levels of both innate… and adaptive cytokines… as well as IFN-associated chemokines and soluble TNF superfamily members weeks before clinical disease flare.”
That work underscored that no single biomarker was likely to predict disease flares in all populations. Instead, analyzing the balance between inflammatory and regulatory mediators enabled accurate predictions of impending flares in lupus patients. The resulting algorithm was based on the sum of all mediator levels assessed pre-flare, weighted by the Spearman correlation coefficients. That sum was then associated with the SELENA-SLEDAI score at the time of the flare to produce a flare risk index.
“The study of biomarkers continues to be an increasingly invaluable and precise tool in the diagnosis and treatment of disease, and our novel test for assessing the likelihood of lupus-related flares holds great promise for helping rheumatologists manage the often painful and debilitating symptoms of lupus,” Mohan Purushothaman, Ph.D., president, chairman, and CEO of Oklahoma City-based Progentec, said in a statement. “This novel test quantifies in practical, numeric terms the risk that a patient will begin experiencing a flare within the ensuing three months – important, actionable knowledge that can be applied to a patient’s treatment regimen.”
Progentec is developing additional tests on this platform. One of the more advanced, aiSLE™ DX Classification, aims to classify lupus with one blood test. Currently, lupus diagnosis takes an average of six years from the onset of symptoms and involves a variety of blood and urine tests, imaging, and sometimes kidney biopsies. The delay risks damaging organs.
The aiSLE platform also is being developed to predict relapse, determine disease activity, and predict interferon treatment response for multiple sclerosis; to distinguish neuromyelitis; and to identify digital biomarkers for Crohn’s disease.