Researchers Identify Genetic Marker for Lupus in African American Women


A new study published in the journal Arthritis & Rheumatology finds there may be a genetic explanation for the development of systemic lupus erythematosus (SLE) in African American women.


A new study published in the journal Arthritis & Rheumatology finds there may be a genetic explanation for the development of systemic lupus erythematosus (SLE) in African American women.

The study, published on August 20, points to epigenetic changes near interferon-regulated genes early in B cell development. These changes are a “hallmark” of SLE development in African American women, the authors wrote.

“We have identified an aberrant epigenetic signature that developed early in B cell development in African American patients. This observation is consistent with recently published work which identified a SLE-specific epigenetic signature present in the resting naïve B cell stage that persists throughout development in a cohort of Africa American females,” wrote the authors who were led by Devin Absher, Ph.D., of the HudsonAlpha Institute for Biotechnology in Alabama.

The findings are based on an analysis of B cells from 31 African American women and 49 white women.  In the new study, Dr. Absher and colleagues found that CpGs regions of DNA near interferon-regulated genes (such as MX1, IFI44L, USP18 and IFITM1) are hypo-methylated in African American women with systemic lupus from the very earliest states of B cell circulation, which suggest that B cells “might be epigenetically primed for an aberrant immune response in African American SLE patients prior to maturation.”

But when B cells from the white female patients were analyzed, methylation changes were found in mature B cell stages. The difference in DNA methylation between the two groups may explain why the disease severity may present differently in these two groups.

“Epidemiology studies reveal that SLE risk and burden is significantly higher in AA females compared to other affected populations, which could potentially be explained by the more severe epigenetic signature observed in AA females in this work,” the authors wrote.

Of interest in this study, no white patient in this study had lupus nephritis, but many of the African American women did have the condition.

Over the years, scientists have identified multiple genes that may disproportionately predispose women to systemic lupus, which is nine times more frequent in women than men. The condition afflicts 31 of 100,000 people and can manifest in the joints, kidneys, heart, lungs, brain and blood.

While environmental triggers such as infection and drug exposure have been implicated in systemic lupus, B-cells appear to be very important through their role in producing and presenting antigens, cytokines and co-stimulatory factors to T-cells.

It is known that epigenetic dysregulation of B-cell differentiation may be an important mechanism underlying systemic lupus pathogenesis. Researchers have also shown that epigenetic factors play a significant role in the etiology of several other autoimmune diseases.

This is the first-known study to examine genome-wide methylation across the stages of B cell development in African American and white women.  The epigenetic patterns appeared to be different in AA and EA patients, suggesting some mechanistic differences in etiology that may be related to the different clinical paths that these patient populations experience,” the authors wrote.

Previous studies have shown a link between under-methylation or hypo-methylation of certain regions of DNA called CpGs. These DNA changes have been associated with an increased risk for systemic lupus, particularly in different ethnic populations.


By locating the specific DNA region, this SLE-related epigenetic signature coupled with population-specific severity future research can continue explore the role of methylation patterns and their differences between ethnic and racial groups in an effort to risk stratify patients while developing new drugs that target specific stages of B-cell development.


Megan Breitbach, Ryne C Ramaker, Keven Roberts, et al. “Epigenetic Defects in the B cell lineage of Systemic Lupus Erythematosus Patients Display Population-Specific Patterns.”  Arthritis Rheumatol. 2019 Aug 20.  DOI:10.1002/art.41083.

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