Why Does Lupus Discriminate Against African Americans?

New LRI-funded Research Finds Genetic Factors

Dr. Timothy Niewold

That African-Americans are three times more likely than Caucasians to develop lupus and with greater severity is well-known. But we do not know why. With initial grant support from LRI, researcher Dr. Timothy Niewold at the University of Chicago has made great headway in uncovering some of the genes that may predispose African Americans to lupus. This year his work has gained tremendous recognition with several published papers and a sizeable grant from the National Institutes of Health.

Dr. Niewold’s initial proposal hypothesized that African-American patients carry genes that cause them to produce higher levels of interferon-alpha, a critical molecule known to drive lupus progression.

Confirming His Hypothesis

Recently published in Arthritis & Rheumatism, Dr. Niewold’s results showed that interferon-alpha levels are indeed higher in African-American lupus patients. Also stemming from original LRI-funded research, Dr. Niewold’s team had previously discovered differences between Caucasians and African Americans in six genes along the biological pathway involved in producing interferon-alpha.

“By studying the genetics of a multi-gene pathway, we can understand what goes wrong and where in the process we can effectively intervene,” said Dr. Niewold. “Our discovery of these genetic factors affecting the production of interferon-alpha should help us individualize treatment in this disproportionately affected patient group.”

African Americans a Growing Priority in Lupus Research

“The genetics of lupus in minority populations is starting to get the attention it deserves, particularly among African Americans where the problem is greatest,” says Dr. Niewold. “We must address a host of challenges to ensure proportionate representation of African Americans in lupus research studies and clinical trials.”

For instance, while the FDA granted approval to Benlysta® as the first new lupus treatment in 50 years, it was with a significant caveat. The prescribing information was required to note the lack of clinical data in African Americans, and Benlysta developers are mandated to conduct a trial specifically among this patient group.

One obstacle to recruitment of these patients is that most research centers are not located in areas with large African American populations. The University of Chicago is unusual in that 70% of its lupus research participants are African American, so Dr. Niewold could readily recruit patients. Researchers at other universities are beginning to reach out to community medical centers and hospitals to recruit minority patients.

Taking His Research to the Next Level

The NIH shares Dr. Niewold’s interest in finding the cause for lupus prevalence and severity among African Americans, awarding him an RO1 grant of $1.95 million to extend his LRI work on a large scale. The five-year study will look deeper into how inherited genetic abnormalities in the interferon-alpha pathway might contribute to lupus in African Americans and other populations.

Beyond his own study, Dr. Niewold also collaborated with other research groups to discover two additional genes associated with the disease in African Americans. He also contributed biological samples from his patients to an international study on mapping out all of the genes that contribute to lupus in African Americans.

“The LRI funding allowed us not only to pursue this new research direction in my own lab but also led us to new collaborations and participation in large-scale international efforts. These synergies among scientists throughout the world will help accelerate the path to discovery.”