08 October 2020
2 minutes to read
Source / Disclosures
James J. Association of environmental factors with the onset of SLE disease. Presented at: Annual Meeting of Clinical Rheumatology-West; October 8-11, 2020 (virtual meeting).
Disclosures: James reported that he sits on the Novartis Advisory Board and that OMRF is associated with Progentec Biosciences.
Understanding the interplay between environmental, genetic and other factors is essential for the management of lupus, according to a presenter at the 2020 Congress of Clinical West Rheumatology.
“We are not necessarily in our childhood, but maybe in our toddler phase”, Judith A. James, MD, PhD, Lou C. Kerr, biomedical research chair, associate vice president for clinical and translational sciences, and George Lynn Cross research professor at Oklahoma University Health Sciences Center, said he understands the environmental factors of lupus.
James covered a wide range of potential environmental contributors to lupus in his speech, from sun exposure, tobacco and alcohol use and weight to sleep patterns, vitamin D intake, mental health and the diversity of the gut microbiome.
Regarding sun exposure, James noted strong links between ultraviolet (UV) exposure and glare. âUp to 93% of lupus patients have some degree of UV sensitivity,â she said, adding that the researchers had spent a lot of time studying these associations.
Judith A. James
The results of these analyzes have provided clinicians with a number of clues, ranging from DNA damage to cellular apoptosis, as part of UV exposure. More specifically, UV-B exposure led to the expression of TNF-alpha and cytokines, in addition to recruiting dendritic cells, keratinocytes and interleukin (IL) -6 in the skin. âBe careful to wear sunscreen,â James said.
According to James, associations between smoking and lupus parameters are also highlighted. She suggested that smoking may increase the risk of developing SLE, while current smoking may increase flare-ups 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. Although higher levels of C reactive protein (CRP) have been observed in smokers with lupus, they are “not found in all studies,” according to James.
Beyond smoking, James presented results showing that moderate alcohol consumption actually had a lower risk of lupus than not drinking, but she quickly noted that most doctors did not encourage it. moderate alcohol consumption in their patients.
Perhaps more importantly, James pointed out that mental health variables are often linked to alcohol use. Depression, post-traumatic stress disorder (PTSD), a history of childhood trauma or physical or emotional abuse can all be environmental risk factors for lupus. âChildren who have been exposed to abuse also have higher rates of lupus,â she said.
One of the environmental factors that capture the attention of lupus experts, according to James, is sleep. A recent study examining a multitude of factors found that insufficient sleep – defined as less than 7 hours per night – was the only factor associated with the transition from no lupus to lupus. âIt will be something we reflect on as we move forward,â she said.
Another factor under study is vitamin D intake. Recent findings have shown that significantly reduced levels of vitamin D may be associated with the development of autoantibodies associated with lupus. Additionally, people who are deficient in vitamin D may have higher levels of interferon activity (IFN) compared to those who have sufficient levels of the vitamin. âI think we’ll see more and more of these studies, where you take an environmental factor and marry it with a genetic predisposition,â James said.
On the frontier of lupus research lies the microbiome, according to James. She raised the question of how bacteria living in the gut can lead to systemic disease like lupus.
The âleaky gutâ hypothesis has been proposed, where bacteria are âtranslocatedâ from other parts of the gastrointestinal tract to the liver. This can induce the production of Th-17 cells. “Some [bacteria] can go in and trigger B cell responses, âshe said.
T-cell responses can also be activated with bad commensal bacterial species, according to James. But these associations are by no means final. âWe still have a lot to learn about what the microbiome does in the development of lupus and the pathogenesis of the disease,â she said. “But we are learning.”