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Publications of the Week

High Prevalence and Disease Correlation of Autoantibodies against p40 Encoded by Long Interspersed Nuclear Elements (LINE-1) in Systemic Lupus Erythematosus

By August 5, 2019No Comments

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This week we profile a recent publication in Arthritis & Rheumatology from the laboratory
of Dr. Tomas Mustelin (pictured, right) at the UW Department of Medicine.

Can you provide a brief overview of your lab’s current research focus?

My lab currently focuses on exploring the molecular mechanisms that underpin rheumatoid arthritis and lupus. We believe that a deeper understanding of these mechanisms is necessary for the discovery and development of better medicines to treat, and perhaps one day to cure, these serious conditions that afflict millions of Americans. Our research tests new hypotheses in patients’ blood cells and correlates experimental findings with clinical characteristics and laboratory measures of the disease in each patient.

What is the significance of the findings in this publication?

This paper describes evidence that a retroelement in our genome, called LINE-1, is active in patients with lupus and results in the development of autoantibodies against one of the two proteins encoded by LINE-1, called p40 or Orf1p. This discovery means that p40 is of prime interest to the immune system in lupus, most likely because it is a remnant of an ancient retrovirus and still has some virus-like features, such as stimulating the production of interferons just like a virus would. We found that the anti-p40 autoantibodies correlate strongly with active lupus, disease flares, nephritis, complement consumption, and many laboratory measures of active lupus.

What are the next steps for this research?

Next, we are exploring the presence of p40 in lupus patients, its ability to drive interferons, and whether it can be stopped with the right drugs.

This work was funded by:

Our work on LINE-1 was supported by NIH grant R21 AR075134.

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