Why do patients with lupus develop neuropsychiatric symptoms?
Systemic lupus erythematosus, also known as SLE or lupus, is an intractable autoimmune disorder that causes inflammation that affects multiple organs. Approximately 75% of all cases show neuropsychiatric symptoms such as encephalopathy, anxiety, depression, strokes, and seizures, which are collectively known as central nervous system (CNS) lupus. However, how lupus influences the brain is largely unknown.
Researchers, headed by Dr. Michael Carroll at Harvard Medical School, have now identified that the type I interferon (IFN) signaling may be involved in CNS lupus. Besides, they have found that a drug that blocks this signaling may inhibit neuropsychiatric symptoms in lupus and other CNS disorders. Findings of their study have been published in the prestigious journal Nature.
Much evidence supports an important role for IFNα in the pathogenesis of SLE. IFNα is a cytokine protein that belongs to the type I IFNs, and it is a component of the innate immune system. When binding to its receptors, IFNα can induce a cascade of immune activity. But it remains unclear whether it could cross the blood brain barrier (BBB) and trigger immune responses in the brain.
To better understand this, Dr. Carroll and colleagues used lupus-prone mice. They found that IFNα permeated the BBB and stimulated microglia -- the cells that form the active immune defense in the CNS -- to become reactive, leading to synapse loss. The researchers also found that the synapse loss could be prevented by blocking type I IFN signaling. These findings combined with the observation of elevated type I IFN signaling in the brain of patients with lupus suggest that inhibiting type I IFN signaling may be a way to combat lupus.
To test this hypothesis, Carroll's team administrated anifrolumab, a type I IFN-receptor antagonist, to mice with lupus. Anifrolumab treatment showed neuro-protective effects. Compared to the control mice, the mice treated with anifrolumab had less behavioral signs of mental illness.
In summary, the study links IFNα to synapse loss in mice with lupus. This discovery provides an explanation for neuropsychiatric symptoms observed in patients with lupus, and may also have implications in other CNS disorders.
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