Lupus: 3 Things to Know

December 3, 2018

What’s new: (1) Gut bacterium may trigger autoimmune disease; (2) pregnancy complications in SLE have declined; (3) childhood abuse raises lupus risk.

Three new studies in systemic lupus erythematosus (SLE) reveal that a gut bacterium may be linked to autoimmune diseases, including SLE; pregnancy complications in women with lupus have decreased over the past 2 decades; and physical or emotional abuse in childhood raises the risk of lupus.^1-3 Scroll through the slides for the latest findings and their clinical implications.

A molecular model that compared a protein encoded by Bacteroides fragilis and human ubiquitin predicted a high level of structural similarity. The immune system of some persons who had been exposed to the B fragilis protein resulted in the generation of immune globulin G antibodies. Serum from patients referred for firstâtime testing to an immunology laboratory for autoimmune disease was more likely to have a high level of antibodies to this protein than serum from healthy volunteers.¹

Clinical Implications: “We have found that some people with autoimmune disease have high levels of antibodies to the bacterial mimic of ubiquitin. It is also possible to have antibodies to both the human and the bacterial mimic. We now need to work out if the mimic of ubiquitin sets up the mistaken immune response. We may then be able to diagnose some autoimmune diseases early and eventually be able to prevent some of them from happening,” said Dr Linda Stewart, Lecturer at the School of Biological Sciences and Institute for Global Food Security at Queen’s University in Belfast, Ireland. “We now want to see if we can make a rapid test that will tell us how much antibody people have so that we can quickly see any changes. We hope that this will allow early diagnosis of disease.”

Yearly retrospective trends of cross-sectional data from the National Inpatient Sample database were analyzed from 1998 to 2014. The analysis included 87,065 pregnant women with systemic lupus erythematosus (SLE) and more than 70 million pregnant women without SLE who had been hospitalized in the US.

Pregnant patients with SLE tended to be older, with a higher proportion of African Americans. They had higher maternal mortality and intrauterine fetal death rates than those without SLE. Patients with SLE also had increased obstetric as well as maternal complications and comorbidities compared with patients without SLE. Maternal mortality and intrauterine fetal death declined over time at a greater rate among patients with SLE than among those without SLE.²

Clinical Implications: “It is very encouraging to see steady improvement in maternal mortality and intrauterine fetal death, and to see that the improvements in fact outpaced improvements for non-SLE pregnancies, indicating that the new information is being adopted and is having an effect,” said senior author Bella Y. Mehta, MBBS, MD, a rheumatologist at the Hospital for Special Surgery in New York. “Our study confirms that currently identifiable risk factors and pregnancy management practices can be used in counseling and pregnancy planning. That SLE pregnancy risk is still higher than risk for non-SLE pregnancies indicates a need for continued research in this area.”

An examination of data on 67,434 women participating in the Nurses’ Health Study II, a longitudinal cohort of female, US-based nurses who enrolled in 1989 and completed health questionnaires every 2 years, identified 93 cases of lupus. After age and race were taken into account, exposure to the highest versus the lowest physical and emotional abuse levels was associated with a more than twofold greater risk of developing lupus.³

Exposure to moderate or high levels of physical assault was associated with 1.7 higher risk of lupus compared with no exposure to assault. Adjusting for potential confounders as well as lifestyle and reproductive factors only modestly attenuated these associations. There was no statistically significant association between sexual abuse and lupus risk.

Clinical Implications: “Exposure to abusive symptoms is surprisingly prevalent. The strong association observed between childhood abuse and lupus risk suggests the need for further research to understand biological and behavioral changes triggered by stress combined with other environmental exposures. In addition, physicians should consider screening their patients for experiences of childhood abuse and trauma,” said lead author Candace H. Feldman, MD, ScD, Assistant Professor, Harvard Medical School, in Boston.

References

1. Stewart L, Edgar JDM, Blakely G, Patrick S. Antigenic mimicry of ubiquitin by the gut bacterium Bacteroides fragilis: a potential link with autoimmune disease. Clin Exp Immunol. 2018;194:153-165. doi: 10.1111/cei.13195.

2. Luo Y, Xu J, Mehta BY. Pregnancy in Lupus: 17-Year U.S. Nationwide Trend in Obstetric and Maternal Outcomes [abstract]. Arthritis Rheumatol. 2018;70(suppl 10).

3. Feldman CH, Malspeis S, Leatherwood C, et al. Association of Exposure to Childhood Abuse with Incident Systemic Lupus Erythematosus in a Longitudinal Cohort of Women [abstract]. Arthritis Rheumatol. 2018;70(suppl 10).

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Lupus: 3 Things to Know

Mark L. Fuerst