The road to lupus — a biologically diverse autoimmune disease with a complex pathogenesis — isn’t a straight line, but people who end up at that final destination, or don’t, may have similarities or markers that led them there, according to Judith James, MD, PhD.
“All of my work goes back to trying to come up with what it would take to eliminate lupus,” said Dr. James, Vice President of Clinical Affairs of the Oklahoma Medical Research Foundation, during the Paul Klemperer, MD, Memorial Lecture: The Winding Road to Lupus. “Historically, we’ve thought about how we better treat (lupus), how we make patients feel better … But if we want to eliminate lupus, we need to understand early events and how we can stop things before it’s too late. This will require preclinical cohorts, better understandings of early pathogenesis, predictors of transitions and mechanisms of non-transitions, and, of course, prevention, which would be the goal.”
Dr. James reviewed a variety of studies, including a Department of Defense Serum Repository, which found that arthritis and discoid lesions are early clinical features of lupus, and also found that associated autoantibodies occur before the onset of linked clinical symptoms.
Another study showed that individuals who do transition to lupus have abnormal immune systems for years, maybe even decades, before they actually become lupus patients, she said, noting that they also have abnormal cytokine profiles years before disease classification.
An Oklahoma Immune Cohort study helped determine the mechanisms of non-transition in the people who don’t develop lupus.
“Autoantibody-positive healthy individuals, these are people who start down the winding road, but find a way to take a detour and never make it to lupus because they have enhanced regulatory mechanisms and suppressed inflammatory responses compared to individuals who transition to SLE,” Dr. James said.
A Nurses Health Study and Black Women’s Health study looked at epidemiological factors associated with lupus, including hormonal influences (menarche, oral contraceptive use, postmenopausaul hormone use, and endometriosis), smoking, and obesity.
A study evaluating psychosocial factors in lupus found that depression is elevated at baseline in individuals who become lupus patients as well as having prior history of PTSD, in addition to childhood physical and emotional abuse.
Dr. James also reviewed studies that look at family members’ risk of transition to lupus.
“Many family members of lupus patients find a way to either camp out on the road or get off the road to lupus, but those who do make it farther down the road have increased genetic risk, have autoantibodies, and some of them have higher CSQ scores, higher levels of stem cell factor, lower level of TGF-β years before they go on to become a lupus patient,” she said.
Dr. James encouraged clinicians to remind family members with negative ANA and no symptoms to quit worrying and worry about other things.
“But if you have family members who are really stressed about whether they’re going to develop lupus … there are some lifestyle choices that may help them,” she said. “We don’t know this, we don’t have data, but we do have data that these things are associated with lupus transition and are good ideas, anyway: smoking cessation, getting an adequate amount of sleep, and normalizing vitamin D levels.”