Alliance Backs SLE Research by Minority Scientists

Marta Figueiredo, PhD avatar

by Marta Figueiredo, PhD |

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The Lupus Research Alliance (LRA) has awarded a total of $2.1 million to five research projects from underrepresented minority scientists focused on the development of tests and treatments for systemic lupus erythematosus (SLE).

“We congratulate the inaugural recipients of our Diversity in Lupus Research Awards and look forward to seeing how their research findings advance our understanding of lupus and result in the development of new treatment options for lupus patients,” Teodora Staeva, PhD, LRA’s chief scientific officer, said in a LRA press release.

The awards are meant to encourage the development of talented early-career researchers and postdoctoral fellows from underrepresented minorities.

“The Career Development and Postdoctoral Awards to Promote Diversity in Lupus Research funding mechanisms are our most recent initiatives to alleviate the disparities that are prevalent in both autoimmune diseases and biomedical research,” Staeva added.

In people with SLE, the immune system wrongly recognizes the body’s own molecules as foreign, producing autoantibodies and mounting responses against them. This ultimately leads to damage in tissues and organs, such as the skin, joints, kidneys, heart, lungs, and nervous system.

According to the LRA, more than 90% of lupus patients are women, and Ancestrally African, South and Central American, and Native Americans are two to three times more likely to develop SLE than Americans with European ancestry.

Since lupus symptoms may vary from person to person and often overlap with those of other diseases, its diagnosis often is difficult and delayed. In addition, no single blood or imaging test can diagnose the disease, further highlighting the need for improved, specific diagnostic tools.

The identification of new SLE-specific targets also is expected to help develop better therapies for the disease.

The Career Development Award to Promote Diversity in Lupus Research, which provides up to $600,000 over four years, was given to three early-career minority scientists: Ashira Blazer, MD, Andrea Knight, MD, and Erika Moore, PhD.

Blazer, of the Weill Cornell Medical College’s Hospital for Special Surgery (HSS), in New York, intends to tackle an unmet need in SLE: the lack of a non-invasive test to detect the progression of lupus nephritis. Lupus nephritis is a common SLE complication characterized by kidney inflammation that  ultimately can lead to kidney failure, and that is more common among patients with African ancestry.

Building upon her preliminary research — in which a urine-based test could distinguish patients with or without lupus nephritis — Blazer will assess the test’s potential clinical use in a large, international SLE patient group with African ancestry.

The test analyzes the urinary sediment, the biological elements of urine such as immune cells and microbes, and the researcher will evaluate potential links between these cells and lupus nephritis and treatment outcomes. This work will provide an opportunity to better understand lupus nephritis in a high-risk and understudied patient group.

The project led by Knight, with the University of Toronto’s Hospital for Sick Children, in Canada, will seek to find ways to identify which adolescents with childhood-onset SLE are at higher risk of structural brain changes that are linked to cognitive problems.

Adolescents with and without lupus will be recruited for a three-year study in which they will complete several tests. Knight’s team will compare the levels of inflammatory and brain injury markers in the blood between the groups, in combination with data from brain MRIs and cognitive function tests.

By doing so, the researchers hope to detect high-risk patients early on to prevent the progression of cognitive impairment.

Moore, of the University of Florida, will use her funding to understand how ancestry influences lupus-related blood vessel inflammation (vasculitis), which may help to advance treatments for patients at higher risk of developing cardiovascular disease.

The researcher will look at monocytes, a type of immune cell involved in SLE and in vasculitis in other conditions, in women of African and European ancestry, with and without lupus.

Two promising postdoctoral research fellows, Ruth Fernandez Ruiz, MD, of the Weill Cornel’s HSS, and Vanessa Wacleche, PhD, with Harvard Medical School’s Brigham and Women’s Hospital, are recipients of the Postdoctoral Award to Promote Diversity in Lupus Research.

This award provides $170,000 over two years to support the generation of data needed for fellows to become independent lupus researchers.

Ruiz hopes to understand how a gene variant in the PRKG1 gene — previously associated with high levels of interferon alpha, an inflammatory molecule implicated in lupus development and progression — influences the disease.

The fellow will analyze several immune cells involved in the production of interferon alpha or in the regulation of lupus-associated inflammation from patients with and without the PRKG1 genetic risk variant. The work may help identify new therapeutic targets to reduce inflammation in SLE patients.

Wacleche’s project will be based on previous findings suggesting that a type of immune cell, called T peripheral helper (Tph) cell, promotes the production of organ-damaging autoantibodies via a pro-inflammatory molecule called CXCL13. CXCL13 is thought to bind to the CXCR5 receptor protein at the surface of B-cells, the immune cells responsible for producing both normal antibodies and autoantibodies.

Wacleche will use innovative technologies to study how Tph cells regulate CXCL13 production and whether interferon-alpha is involved in this process. This information may help identify ways to suppress CXCL13 production, which eventually may represent new therapeutic strategies in SLE.