Increased disease activity is associated with altered sleep architecture in an experimental model of systemic lupus erythematosus

Abstract

SLEEP IS VITAL TO HEALTH AND QUALITY OF LIFE, WHEREAS POOR SLEEP IS ASSOCIATED WITH ADVERSE HEALTH CONSEQUENCES. THIS IS AN IMPORTANT issue in its own right because sleep deprivation is becoming a more frequent and more accepted occurrence in modern society. In addition, sleep disorders have been observed in a number of chronic inflammatory conditions such as autoimmune diseases. Some of the clinical states associated with sleep disturbances include rheumatoid arthritis, fibromyalgia, and systemic lupus erythematosus (SLE).1 Nevertheless, it is unclear whether the sleep disruption that is observed in patients with these diseases is a result of factors associated with the disease—such as pain, depression, and stress2—or the result of dysregulation of the relationship between sleep and the immune system. Sleep disturbances are often reported by patients with SLE, and this may be associated with fatigue,3 a symptom that affects up to 80% of patients with SLE.4 According to Valencia-Flores and colleagues,5 these patients are sleepier during the day by virtue of sleep fragmentation due to more arousals and sleep-stage transitions (SST). In addition, the disease is exacerbated by sleep disruption, resulting in decreased sleep efficiency and less delta sleep. Additional polysomnographic findings associated with disease activity include an increased percentage of stage 1 sleep and alpha intrusions into non-rapid eye movement sleep. Furthermore, sleep apnea, periodic leg movements during sleep and narcolepsy have been associated with SLE.6 Much of our current knowledge of the pathogenesis of SLE is based on inference from a murine model, the New Zealand Black/New Zealand White (NZB/NZW)F1 hybrid strain. These mice spontaneously develop an autoimmune disease that closely resembles the immunologic and clinical characteristics of human SLE, such as high titer levels of antinuclear antibodies (ANA) associated with the development of rapidly progressive and lethal glomerulonephritis. Similar to its characteristics in humans, the disease is most common in female mice. However, there is no evidence about sleep patterns in this experimental model of SLE. Recent data from our laboratory indicate the importance of adequate sleep in (NZB/NZW)F1 mice. We observed that mice submitted to sleep deprivation exhibited an earlier onset of the disease, as reflected by the increased ANA titer levels.7 The purpose of the present study was, therefore, to evaluate the sleep patterns in a spontaneous experimental model of SLE, which offers a great opportunity to study the interaction between sleep and autoimmune disease. The disease course in (NZB/NZW)F1 mice was also assessed by following the development of ANA and pain sensitivity. A characterization of the sleep architecture that is associated with the onset, progress, and severe phases of this disease is presented in this article.