In a review published in 2019, Dr. James’ laboratory collaborated with rheumatology researchers from the University of Colorado to compare elevations of soluble mediators that precede both clinical SLE and rheumatoid arthritis (RA) in patient cohorts from the U.S. military. Within one to two years before patients meet the classification criteria for RA, certain cytokines and chemokines, including IL-6, IFN-c and TNF-b, dramatically increase. In lupus, cytokines and chemokines elevate within the final year before classification, with BLyS ramping up very close to diagnosis, she said.7
Risk Influencers
Research teams are using very large patient cohorts, such as the Nurses’ Health Study I and II, and the Black Women’s Health Study, to identify epidemiological factors, including age at menarche, smoking status, obesity and alcohol use, that may influence lupus risk. Nurses’ Health Study data were used to show that moderate drinking is somewhat protective when it comes to lupus risk in women, and depression is associated with elevated SLE risk.8,9
Relatives of SLE patients often ask Dr. James about their risk of developing lupus or other autoimmune diseases. She and her colleagues studied patients and first-degree relatives of people with SLE and RA in a study published in 2019.10 They examined serum samples from family members to look for disease-specific autoantibodies and tested samples for antibodies against thyroid disease, celiac disease and type-1 diabetes. The study grouped patients as having alternative autoantibodies if they had at least one autoantibody not associated with their relative’s autoimmune disease and having expanded autoimmunity if they had autoantibodies associated with two or more different diseases.
SLE patients’ relatives were more likely than RA patients’ relatives to have either alternative or expanded autoimmunity. Alternative autoimmunity was primarily systemic in the SLE cohort, while it was organ-specific in families of patients with type-1 diabetes. People in the RA cohort were more likely to have both systemic and organ-specific alternative autoimmunity, and they had mostly anti-TPO antibodies.
In a follow-up study, Dr. James and her collaborators studied blood samples from lupus patients’ relatives to look for factors that may indicate which autoantibody-positive relatives had the highest risk of transitioning to lupus. They identified 45 relatives of lupus patients from lupus genetics studies who had transitioned to having four or more ACR SLE classification criteria during a mean follow-up period of 6.4 years; 73.8% were European American, 14.7% were African American, 2.5% were Hispanic and 9% were from other ethnic backgrounds, including Native Americans. European Americans had the lowest transition rate, 0.81 transitions per 100 follow-up years, while African Americans had 1.45 transitions and Native Americans had 2.27 transitions.11