Advances in Precision Medicine in Lupus

Oct 15, 2019

In a review that examines the use of conventional and orphan autoantibodies as biomarkers for diagnosing systemic lupus erythematosus (SLE), researchers say the science is advancing rapidly with the goal of diagnosing lupus earlier than currently done.

In a review that examines the use of conventional and orphan autoantibodies as biomarkers for diagnosing systemic lupus erythematosus (SLE), researchers say the science is advancing rapidly with the goal of diagnosing lupus earlier than currently done.

The review, by researchers with the University of Calgary in Canada, was published online August 9 in the journal Lupus.

“The use of autoantibodies holds promise to predict the onset, phenotypes, remissions, exacerbations and prognosis of SLE,” the authors state.

While the use of conventional and orphan autoantibodies have already improved the diagnostic accuracy in lupus, much more needs to be done, particularly in diagnosing early disease. “Meaningful prospective studies of autoantibodies are required, but to do so requires careful consideration of the cohorts that should be studied, which autoantibodies and clinical parameters will be measured, and which immunoassays will be used to measure them with anticipation that genomic, epigenomic, proteomic and metabolomic studies can add value to the predictive
power of autoantibodies,” the authors wrote.

THE REVIEW

The authors reviewed the various autoantibodies and their know roles in systemic lupus erythematosus as well as present a p-value matrix designed to improve the accuracy of predicting lupus early.

Circulating autoantibodies directed against a multitude of intracellular and extracellular components are the hallmark of systemic lupus erythematosus. Through decades of rigorous study, the pathogenic role of autoantibodies against extracellular targets has been revealed while intracellular mechanisms remain elusive.

See next page:  "Using autoantibodies and antinuclear antibodies in clinical medicine are based on three tenants."

Using autoantibodies and antinuclear antibodies in clinical medicine are based on three tenants:

• Disease prevention
• Early and accurate diagnosis
• Timely and effective treatment

To these three ends, antinuclear antibody testing can occur in the primary care setting with the intent to refer if screening is positive. Patients with symptoms present for establishment or confirmation of diagnosis with the intent to treat. Antinuclear antibody testing may allow for earlier and accurate diagnosis with the intent to prevent systemic lupus erythematosus or its consequences.

“If auto-antibodies and other biomarkers can predict the onset of SLE, the out- comes are likely to be better and decrease direct and indirect health-care costs,” the authors wrote.

The p-value matrix presented in this article aims to describe the various utilities and functional domains of systemic lupus erythematosus and how autoantibodies act as biomarkers for diagnosis and prognosis. The p-value matrix describes specific autoantibodies and relates them to outcomes.

The p-value matrix of autoantibodies in systemic lupus erythematosus:
• Pathogenic/Lethal
- double stranded DNA, nucleosome, C1q-renal
• Protective/Preventive
- U1RNP-renal
- Double stranded DNA---cancer
• Predictive
-     Ro60/SSA, Sm, double stranded DNA
• Prognostic
-     Nucleosomes/chromatin: kidney failure
• Precise
-     High specificity for SLE
-     Sm, double stranded DNA
• Passe, Perplexing, Esoteric, Indifferent, Chaff=Orphan antibodies

The matrix allows us to use antibody testing to predict severity of disease and risk stratify patients with systemic lupus erythematosus. The authors also point out that many autoantibodies thought to be “junk” are actually important if misunderstood and as such they chose to refer to them as orphan autoantibodies.

Predicting the development of systemic lupus erythematosus before development of the disease would be a significant advancement possibly leading to prevention. There is compelling evidence that autoantibodies can predict flares, remission, and clinical prognosis in other autoimmune diseases.

Predictive autoantibody studies are very challenging owing to the complexity, variable course and prolonged periods of observation needed in systemic lupus erythematosus. The fact that autoantibodies and antinuclear antibodies are present in nearly one-quarter of healthy individuals further complicates their use in predicting lupus.

The increasing availability of multiplexed array technologies in high-throughput laboratories allows for the detection of a large number of autoantibodies in a small serum sample. This technology has markedly improved the ability to predict the onset and course of systemic lupus erythematosus.

The authors conclude that autoantibodies are important biomarkers that may function as predictive, prognostic, pathogenic protective and precise indicators in systemic lupus erythematosus. Unfortunately the vast majority of autoantibodies in lupus fall into the category of orphan autoantibodies awaiting a determination of significance.

With meaningful prospective studies autoantibodies hold promise in predicting the onset, phenotypes, remissions, exacerbations and prognosis of systemic lupus erythematosus.

The technology available to us today makes finding biomarkers able to predict systemic lupus erythematosus even before it strikes a real possibility in the not so distant future. These finding provide hope to patients suffering with lupus and a basis for researchers and clinicians to make strides towards treating and even preventing systemic lupus erythematosus.

REFERNCE:

Choi, M. Y., Fritzler, M. J. “Autoantibodies in SLE: prediction and the p value matrix.”Lupus. 2019 Oct;28(11):1285-1293. doi: 10.1177/0961203319868531. Epub 2019 Aug 9.

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