Determining a Mechanism for Nervous System Lupus

By Anna Tarasova ’19

Figure 1: Type 1 IFN protein.

Figure 1: Type 1 IFN protein.

Systemic lupus erythematosus (SLE) is an uncommon but debilitating autoimmune disease that is accompanied by psychiatric and neurological symptoms in 75% of cases. SLE with these neuropsychiatric symptoms that include depression, anxiety, and seizures is known as CNS lupus. The mechanism behind CNS lupus has long been a mystery.

Dr. Allison Bialas and her team analyzed SLE progression in a lupus-prone mouse strain. 50-80% of SLE lupus patients express type I interferons (IFN), which elevate the immune response. Type I IFN interact with IFNAR receptors, which are found on microglia, the immune cells of the nervous system. When this interaction occurs, the microglia begin to engulf surrounding nervous tissue, including neuronal and synaptic material. This mechanism could explain the complex of neuropsychological symptoms that can further complicate a diagnosis of SLE.

In this study, lupus-prone mice were treated with IFNAR-blocking antibody to evaluate the role of IFNAR in promoting microglia function as part of CNS lupus. The IFNAR-blocking treatment was found to significantly lower the number of reactive microglia. Less reactive microglia could mean less engulfment of neural tissue and thus less lupus-related neurological symptoms. Following their experiments with IFNAR, the researchers used transmission electron microscopy (TEM) to determine what types of neuronal tissue were affected by the overactive microglia. Synapses or points of contact between neurons, were found to be the type of tissue most frequently damaged. The reason for this, however, remains unclear.

CNS lupus patients can be left out of clinical trials because neuropsychological symptoms can make testing treatments more difficult and the process through which lupus affects the brain is unknown. In the future, treatment with IFNAR blockers may alleviate the psychological aspect commonly present in lupus and allow these patients to participate in studies.

 

References:

  1. A. Bialas et al., Microglia-dependent synapse loss in type I interferon-mediated lupus. Nature, 2017. doi: 10.1038/nature22821
  2. https://upload.wikimedia.org/wikipedia/commons/f/fb/1AU1_Human_Interferon-Beta01.png
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