Clinicians must account for myriad environmental factors when managing lupus
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Understanding the interplay between environmental, genetic and other factors is critical to lupus management, according to a presenter at the 2020 Congress of Clinical Rheumatology-West.
“We are not necessarily in our infancy, but maybe in our toddler phase,” Judith A. James, MD, PhD, Lou C. Kerr Endowed Chair in Biomedical Research, associate vice provost for clinical and translational science, and George Lynn Cross Professor of Research at the Oklahoma University Health Sciences Center, said of understanding environmental factors in lupus.
James covered a broad range of potential environmental contributors to lupus in her talk, from sun exposure, tobacco and alcohol use and weight to sleep habits, vitamin D intake, mental health and gut microbiome diversity.
Regarding sun exposure, James noted strong links between ultraviolet (UV) exposure and flare. “Up to 93% of lupus patients have some degree of UV sensitivity,” she said, adding that researchers have spent significant time investigating these associations.
Results from these analyses have provided clinicians with a number of clues, from DNA damage to cell apoptosis, in the setting of UV exposure. More specifically, UV-B exposure has led to expression of TNF-alpha and cytokines, in addition to recruiting dendritic cells, keratinocytes and interleukin (IL)-6 to the skin. “Be careful to wear sunscreen,” James said.
Associations between smoking and lupus parameters are also coming into focus, according to James. She suggested that ever smoking can increase risk of SLE onset, while current smoking can increase flares or decrease the effectiveness of hydroxychloroquine.
Biological evidence has shown that smoking can decrease natural killer (NK) cells, impair humoral immunity and cause changes in DNA methylation. While higher levels of C-reactive protein (CRP) have been observed among smokers with lupus, they are “not found in every study,” according to James.
Beyond smoking, James presented findings showing that moderate drinking actually yielded lower lupus risk compared with no drinking, but she was quick to note that most doctors do not encourage moderate drinking in their patients.
Perhaps more importantly, James stressed that mental health variables often are related to alcohol intake. Depression, post-traumatic stress disorder (PTSD), a history of trauma or physical or emotional abuse in childhood can all be environmental risk factors for lupus. “Children who have been exposed to abuse also have higher rates of lupus,” she said.
One environmental factor that is gaining attention among lupus experts is sleep, according to James. A recent study looking at a host of factors demonstrated that inadequate sleep — defined as fewer than 7 hours per night — was the only factor associated with transitioning from no lupus to lupus. “This will be something for us to think about as we move forward,” she said.
Yet another factor under investigation is vitamin D intake. Recent findings have shown that significantly reduced levels of vitamin D may be associated with the development lupus-associated autoantibodies. In addition, vitamin D deficient individuals may have higher levels of interferon (IFN) activity compared with those who have sufficient levels of the vitamin. “I think we will see more and more of these studies, where you take an environmental factor and marry it with a genetic predisposition,” James said.
On the frontier of lupus research is the microbiome, according to James. She raised the question of how bacteria living in the gut can lead to a systemic condition like lupus.
The hypothesis of a “leaky gut” has been proposed, where bacteria are “translocated” from other parts of the GI tract to the liver. This may induce Th-17 cell production. “Some [bacteria] can come in and trigger B cell responses,” she said.
T-cell responses may also be activated with wrong commensal bacterial species, according to James. But these associations are by no means definite. “We still have a lot to learn about what the microbiome is doing in lupus development and lupus disease pathogenesis,” she said. “But we are learning.”
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James J. Association of Environmental Factors with SLE Disease Onset. Presented at: Congress of Clinical Rheumatology-West annual symposium; October 8-11, 2020 (virtual meeting).
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