A Call for Better Biomarkers for Systemic Lupus Erythematosus

Malika Ammam, PhD avatar

by Malika Ammam, PhD |

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The promise that the field of biomarkers hold for earlier diagnosis and hence superior treatment of systemic autoimmune diseases were the focus of a recent review in Drug Discovery & Development.

Systemic autoimmune diseases like rheumatoid (RA), systemic lupus erythematosus (SLE), Sjögren’s syndrome (SjS), polymyositis/dermatomyositis, and systemic sclerosis (SSc) are disorders influenced by a number of factors like genetics, immunological mechanisms and the environment. They are defined by changes in autoantibodies reactive to a wide variety of auto antigens like DNA, cell surface molecules, and intracellular matrix proteins.

In general, biomarkers could be used for early disease detection and treatment. Ideally, a biomarker would identify the cause of the disease and its effective treatment. In medical fields relating to tumors (oncology), biomarkers have been successfully used to detect a number of diseases such as BRAF V600E positive melanoma, where patients who carry this mutation were successfully treated with vemurafenib, a drug that targets the mutant protein.

“The need for effective biomarkers in systemic autoimmune disease is critical as many patients are only diagnosed once irreversible damage has begun, and the time for optimal treatment may have passed,” the authors write in their review. “Although there is seemingly a long road ahead before we can begin to match the precision of the best oncology biomarkers, advanced technology in use today can facilitate their development.”

When compared to successful singledriver mutation biomarkers in oncology, biomarkers in systemic autoimmune diseases face many challenges. Nevertheless, a number of promising routes have been discovered and progress is being made in the diagnosis of these diseases.

For example, biomarkers like rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), creactive protein (CRP) and anti-cyclic citrullinated peptide (anti-CCP) were suggested as potential candidates for diagnosis of autoimmune diseases like RA. Furthermore, disease activity (low, moderate and high severity) could be measured through a biomarker-based panel of 12 proteins whose levels are combined into a single score algorithm from one and 100. For other systemic autoimmune diseases, antinuclear antibody (ANA) was proposed to be useful for diagnosis, but lacks specificity.  Some studies, for instance, found that nearly all systemic lupus erythematosus patients test positively for ANA, although most people who test positively for ANA do not have SLE. Tests for other biomarkers (such as anti-dsDNA) were suggested for lupus and lupus nephritis diagnosis. Finally, biomarkers based on antiphospholipid antibodies, anti-Sm, anti-Ro (SSA) and anti-La (SSB) were also considered as candidates in SLE, lupus and SjS diagnosis.

These findings suggest that a number of potential biomarkers could offer promising opportunities in the diagnostic and response to treatment of several systemic autoimmune diseases. However, there is still a long way to go in biomarker research and testing before effective biomarkers are identified that could prove of critical value — leading to more patients with systemic autoimmune disease being diagnosed before irreversible damage occurs and to having a better chance of optimal treatment.