Link between fatigue and brain-reacting autoantibodies in Lupus

The presence of anti-NR2 antibodies is a helpful diagnostic tool and may offer a major new approach in managing fatigue in people with Lupus.

Systemic lupus erythematosus (often called Lupus or SLE) is an autoimmune disease where immune cells in the body become hyperactive and produce autoantibodies. It typically affects women between the ages of 15 and 45, but can also start in younger children, later in life, and in men. There are many things that can trigger Lupus, and symptoms can vary from patient to patient. People with Lupus may have joint pain, and their skin may be sensitive to sunlight, but also inner organs such as the kidney or the brain may be affected. Fatigue is a particular problem for people with Lupus, and has a big effect on their quality of life and ability to work.

An antibody is a protein that the immune system makes to attack foreign substances that enter the body, such as viruses or bacteria. In autoimmune disease, the immune system makes antibodies that attack the body’s own tissues. Antibodies can be detected in a person’s blood.

What did the authors hope to find?
The authors hoped to find a link between fatigue and the presence of a certain type of autoantibody in the blood (called anti-NMDAR). By making this link, they hoped it would be possible to create a tool that could help to measure fatigue. Being able to measure this symptoms might help doctors to tailor treatment for people with Lupus.

Who was studied?
The study looked at blood samples from 426 people with Lupus and compared them to samples from healthy volunteers. Everyone was over the age of 18.

How was the study conducted?
This was a single-centre study at one clinic in Germany. Everyone taking part gave a blood sample, and filled in a questionnaire designed to assess their fatigue. Each person’s blood was analysed for the presence of antibodies to the so-called NMDA-receptor in the brain. In addition, the authors did some lab experiments with the autoantibodies to investigate their effects. The study also looked separately at people who were taking a medicine called belimumab for their Lupus.

What were the main findings of the study?
The authors found that there was a link between fatigue severity and the level of autoantibodies in the blood. They also found that treatment with belimumab for at least 6 months reduced fatigue and levels of antiNMDAR antibodies.

Are these findings new?
Yes. This is the first time that this link has been made.

What are the limitations of the study?
This was a single-centre study. More and bigger studies will be needed to work out whether these brain-reactive autoantibodies can be used to diagnose people with Lupus, and how useful it might be to reduce or eliminate these autoantibodies in people with fatigue.

What do the authors plan on doing with this information?
Additional studies are underway to examine how useful this link might be, and whether it might be possible to improve a person’s fatigue symptoms by reducing their antibody levels.

What does this mean for me?
If you have Lupus, it might be difficult for your doctor to measure your fatigue, or understand how it affects your life. This study suggests there is hope that in the future fatigue will be measured and taken seriously, and also that there might be a way to treat it.

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Date prepared: August 2019
Summary based on research article published on: 11 June 2019
From: Schwarting A, et al. Fatigue in SLE: diagnostic and pathogenic impact of anti-N-methyl-D-aspartate receptor (NMDAR) autoantibodies. Ann Rheum Dis 2019;78:1226–34. doi:10.1136/annrheumdis-2019-215099

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