Patients with chronic sleep deprivation at higher risk for lupus
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Individuals with chronic sleep deprivation demonstrate a higher risk for developing systemic lupus erythematosus, with stronger effects in those with depression and bodily pain, according to data published in Arthritis Care & Research.
“Sleep deprivation is an underrecognized public health concern that is increasing in prevalence worldwide,” May Y. Choi, MD, MPH, of Brigham and Women’s Hospital and Harvard Medical School, and colleagues wrote. “A challenge in studying sleep duration and SLE is that there may be many potential confounders and effect modifiers, including pain, depression, shiftwork and hormonal status, that need to be considered.”
To investigate the impact on chronic sleep deprivation on the development of SLE, Choi and colleagues analyzed data from two cohorts from the Nurses’ Health Study. The cohorts were established in 1976 and 1989, and include 121,700 and 116,430 married female registered nurses, respectively. Participants received mailed questionnaires assessing details regarding the development of new diseases and lifestyle factors. Patients were excluded from the analysis if they had prevalent SLE or other connective tissue disease at baseline.
Participants in both cohorts provided information regarding the total number of hours of “actual sleep” they achieved in a typical 24-hour period, the researchers wrote. Responses ranged from 5 hours or fewer to 11 hours or more. Researchers discerned the cumulative average by taking the sum of typical sleep hours and dividing it by the number of assessments reported for that patient. The cumulative averages were categorized as 5 hours or fewer, more than 5 hours but no more than 6, more than 6 hours but no more than 7, more than 7 hours but no more than 8, and more than 8 hours.
Patients who self-reported SLE diagnoses were screened. When screened positively, medical records were attained and reviewed to ensure the patient met the criteria set by the American College of Rheumatology 1997 SLE Classification Criteria.
The analysis included 186,072 participants with 187 incident cases of SLE over a total follow-up period of 4,246,094 person-years.
According to the researchers, chronic sleep deprivation — defined as 5 hours or fewer per night — was associated with a higher risk for developing SLE, compared with those who averaged more than 7 hours but no more than 8 (adjusted HR = 2.47; 95% CI, 1.29-4.75). This association remained even after researchers lagged the analysis by 4 years (adjusted HR = 3.14; 95% CI,1.57-6.29) and adjusted for shiftwork, bodily pain and depression (adjusted HR = 2.13; 95% CI, 1.11-4.1).
The researchers also noted additive interactions between sleep deprivation and high bodily pain — defined as an SF-36 score of more than 75 — with an attributable proportion of 64% (95%CI, 40% to 87%). Meanwhile, the HR for SLE was 2.97 (95%CI, 1.86-4.75) for patients with both risk factors compared with those with neither.
There was an additional interaction between sleep deprivation and depression, with an attributable proportion of 68% (95%CI, 49% to 88%), and an HR of 2.82 (95% CI, 1.64-4.85) for SLE, compared with those without, according to the researchers.
“We found an association between sleep deprivation and SLE risk, potentially exacerbated in those with a history of depression and bodily pain,” Choi and colleagues wrote. “A better understanding of the mechanisms involving the nervous system and immune system that may be underlying the complex interaction between depression, pain, sleep, shiftwork and autoimmune disease development is needed.”
Perspective
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Although treatment options for systemic lupus erythematosus have expanded in recent years the ultimate goal of disease prevention remains elusive. Given the tremendous individual and societal burdens associated with chronic autoimmune disease, identifying any potentially modifiable risk factors is of immense value.
In the current study, Choi and colleagues prospectively examine the association between sleep deprivation and SLE using the very large NHS I and II cohorts and demonstrate a significant association between chronic low sleep — ie, less than 5 hours — and incident lupus risk.
Further, the investigators were able to detect and characterize the additive interactions between low sleep, high bodily pain, depression and their respective contributions to higher risk for SLE. The strongest effects of chronic low sleep duration in terms of SLE risk were observed among individuals with higher bodily pain and depression — an almost 3-fold higher risk vs. women with adequate sleep and no bodily pain or depression.
The authors discuss possible mechanisms to explain the relationship between sleep and the development of autoimmune disease. Previously, experimentally induced sleep deprivation has been shown to increase expression and production of pro-inflammatory cytokines, as well as impair the proper function of T cells and CD4 regulatory T cells in humans. Also, in murine SLE models, sleep deprivation has been associated with earlier onset of disease.
One of the limitations of the study, acknowledged by the authors, is that vitamin D deficiency was not accounted for. Vitamin D deficiency is both common in patients with SLE and has been associated with higher disease activity. This warrants further examination as there is growing evidence that vitamin D deficiency may also play a role in sleep disturbance. Additionally, the NHS I and II cohort populations include women exclusively, and primarily those who are white. Thus, looking at a more heterogeneous study group would be useful to verify if the results are generalizable to the broader lupus population.
Most importantly, future studies should assess the potential reversibility of the immunologic changes associated with sleep deprivation and concomitant disease so that effective lifestyle modification programs might be developed, which in turn might establish a path toward primary prevention of autoimmune diseases such as SLE.
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