Chandra Mohan, Hugh Roy and Lillie Cranz Cullen Endowed Professor of biomedical engineering at the University of Houston, screened more than 1,100 proteins in the fluid surrounding the brains of neuropsychiatric lupus patients and identified a few proteins that could potentially be used to diagnose neuropsychiatric lupus. CREDIT University of Houston

A globally renowned expert in autoimmune diseases and systemic lupus erythematosus (SLE) at the University of Houston has identified potential biomarkers for neuropsychiatric symptoms of lupus. Lupus is an autoimmune disease in which the immune system attacks its own tissues, causing widespread inflammation and tissue damage in the affected organs. 

While most people with lupus experience a variety of symptoms that include fatigue, skin rashes, fever, and pain or swelling in the joints, about half of people with SLE suffer neuropsychiatric symptoms. Those include seizures, aseptic meningitis, acutely confused states, cerebrovascular disease psychosis and mood disorders.  

“The diagnosis of neuropsychiatric lupus is difficult because the neurological symptoms could very well be due to other causes. As no gold-standard diagnostic test exists for neuropsychiatric systemic lupus erythematosus (NPSLE), we executed a broad screen of NPSLE cerebrospinal fluid using an aptamer-based platform,” reports Chandra Mohan, Hugh Roy and Lillie Cranz Cullen Endowed Professor of biomedical engineering, in the journal Arthritis & Rheumatology. Aptamers are short sequences of nucleic acids that can be further selected based on their binding specificities. Commercially available libraries of aptamers allow comprehensive screening of >1000 human protein targets, representing some of the largest screening platforms currently available in targeted proteomics.  

Mohan’s team screened more than 1,100 proteins in the fluid surrounding the brains of neuropsychiatric lupus patients and identified a few proteins that could potentially be used to diagnose neuropsychiatric lupus. The proteins that showed up in most samples are CSF Lipocalin-2, M-CSF, IgM and complement C3.  

“These proteins emerged as promising cerebrospinal fluid biomarkers of NPSLE with diagnostic potential,” Mohan reported. “Elevated CSF C3 was associated with acute confusional state. Eleven molecules elevated in the fluid exhibited concordant elevation in the choroid plexus, suggesting shared origins.” 

Neuropsychiatric events occur most frequently early during the disease course in most cases, either as a presenting symptom or within the first five years of disease onset.  

Cerebrospinal fluid samples used in this study were provided by collaborators John Hanly from Dalhousie Lupus Clinic, Halifax, Nova Scotia, Canada and C.C. Mok from Tuen Mun hospital in Hong Kong, China. Laboratory studies were carried out by UH researcher Kamala Vanarsa in Mohan’s lab. 

“We believe proteomic investigations of blood and cerebrospinal fluid will eventually lead to the fabrication of a serum or cerebrospinal fluid-based diagnostic panel that permits accurate diagnosis of NPSLE, with significantly higher specificity for this disease, compared to other neuroinflammatory diseases or infections,” said Mohan.  

The Lupus Research Alliance (LRA) and its clinical affiliate Lupus Therapeutics (LT) announced two major initiatives to address underrepresentation of minorities in clinical trials and in the scientific research profession: Project CHANGE by LT and the Diversity in Lupus Research Program. The organization has tackled these disparities for decades and now embarks on this highly aggressive multi-pronged plan to achieve equity among people with lupus and professionals in this field.

Project CHANGE by LT to Increase Lupus Clinical Trial Participation among African Americans
Led by newly appointed Health Equity Director Ebony Scott, the Lupus Therapeutics Project CHANGE by LT: Community-based Health Action Network to Generate Trial Participation and Eliminate Disparities focuses on a community-based participatory research approach, health inequities and disparities in clinical trials. Under her direction, this program will develop multifaceted, comprehensive action plans that increase meaningful, equitable, and supported clinical trial awareness, participation, and retention (engagement) among African Americans diagnosed with lupus in the U.S. A collaborative team in three pilot locations will work with patients; hospitals; healthcare providers; women’s health groups; medical and nursing associations; medical, community-based, faith-based, and grass root organizations; as well as community leaders to tailor a specific Action Plan that fits each of their community’s specific and unique needs.

“Because lupus affects each person differently, it is especially important for the full range of patients living with lupus to participate in research so that we can work towards new treatments and ultimately a cure,” noted Ms. Scott. “However, too often treatments are not tested among the people who will need them most. Project CHANGE by LT will increase representation by people of color in lupus clinical research, particularly African Americans, so potential new treatments can be developed that work for each individual.” Watch this video to hear more about the program from Ms. Scott.

Lupus is an autoimmune disease that disproportionately affects people of color in both prevalence and severity of disease.  In fact, lupus is the 5th and 6th leading cause of death among African American and Hispanic females 15-24 and 25-54 respectively – just behind cancer, heart disease and HIV.ⁱ Regarding lupus-specific clinical trials, a recent study found that only 14% of clinical trial participants included African Americans with lupus.^[i]i

LRA Launches Diversity in Lupus Research Program
Another disparity the LRA aims to alleviate is the lagging representation of minorities in the scientific research field. In a 2018 report the National Science Foundation details that African Americans, Pacific Islanders, Native Americans, and Hispanic individuals make up just over 10% of the scientific workforce despite accounting for more than 25% of the general population.[ii]ⁱ

To foster the development of talented underrepresented minority early-career scientists, postdoctoral fellows, and research trainees interested in lupus research, the LRA is launching a comprehensive Diversity in Lupus Research Program. The three key areas include:

• The Career Development Award to Promote Diversity in Lupus Research provides up to $600,000 over four years to outstanding early-career underrepresented minority scientists to establish an independent research program aligned with LRA’s strategic priorities.
• The Postdoctoral Award to Promote Diversity in Lupus Research provides promising underrepresented postdoctoral research fellows with $170,000 over two years to support projects and the generation of data needed to become an independent lupus researcher.
• The Administrative Supplement to Promote Diversity in Lupus Research supports, for up to two years, promising underrepresented minority trainees working with LRA-funded researchers or lupus investigators supported by the National Institutes of Health or Department of Defense who have reviewed LRA grant applications within the past three years.

LRA Chief Scientific Officer Dr. Teodora Staeva noted, “In addition to financial support, the Diversity in Lupus Research Program will provide access to quality mentorship by leading lupus investigators, access to opportunities and resources for scientific and professional development as well as a supportive network of peer scientists, creating a close professional community.”

Building on Partnerships with Well-Respected Groups
These new programs build upon the recommendations of the Lupus Multi-Cultural Engagement Partnership formed by the LRA and the National Minority Quality Forum to address the causes and potential solutions for the lack of inclusion in clinical trials of populations at greatest risk for lupus. A Meeting report, Addressing the Challenges of Clinical Research Participation Among Populations Disproportionately Impacted by Lupus presents many short- and long-terms strategies, some of which LRA has already undertaken and others in progress. The program is part of a multifaceted approach that included the pivotal Lupus Patient-Focused Drug Development (PFDD) Meeting hosted by the LRA, Lupus and Allied Diseases Association and the Lupus Foundation of America which produced a comprehensive report bringing 2,000+ diverse patient perspectives to the U.S. Food and Drug Administration drug review process on what people with lupus need from treatments. The LRA and LT continue to advocate with the FDA on behalf of the lupus community, providing feedback on patient concerns in addition to researching better ways to measure and evaluate the effectiveness and safety of potential new drugs.

Ensuring that the diversity of people with lupus is well represented in clinical research was the objective of a recently completed pilot study, Patient Advocates for Lupus Studies (PALS), a peer support program in which individuals living with lupus were trained to provide others with early education about clinical trials.  The goal of the program was to improve clinical trial awareness, knowledge, and enrollment among people living with lupus, and study results will be available this year.  LRA and LT also has worked with a wide range of groups such as Black Nurses Rock, Balm in Gilead, National Kidney Foundation, as well as clinical trial patient recruitment groups Antidote and Center for Information and Study on Clinical Research Participation (CISCRP) to make sure the full range of groups are knowledgeable about lupus and equipped to self-advocate for clinical trial opportunities.

“We were among the first to identify significant racial disparities in lupus care among underrepresented minority populations and have worked with the U.S. Office of Minority Health, U.S. Office of Women’s Health and the Surgeon’s General to conceptualize The Lupus Initiative run by the American College of Rheumatology and educate healthcare providers to improve diagnosis, prompt treatment and encourage racially diverse participation in clinical studies,” commented LRA President and CEO Kenneth M. Farber. “Ensuring that minorities are well-represented in clinical trials is a major priority for us. Building on this strong foundation, our work continues with renewed focus to achieve greater diversity among professionals researching lupus and engaging patients in clinical trials.”

About the Lupus Research Alliance
The Lupus Research Alliance is the largest non-governmental, non-profit funder of lupus research worldwide. The organization aims to transform treatment by funding the most innovative lupus research, fostering diverse scientific talent, and driving discovery toward better diagnostics, improved treatments and ultimately a cure for lupus. Because the Lupus Research Alliance’s Board of Directors fund all administrative and fundraising costs, 100% of all donations goes to support lupus research programs. 

About Lupus Therapeutics
Lupus Therapeutics, an affiliate of the Lupus Research Alliance, aims to accelerate drug discovery and diagnostic innovation for all patients living with lupus. Lupus Therapeutics engages with biotechnology and pharmaceutical industry, as well as other investigators, to bring clinical trials to real people living with lupus. The organization aims to place the patient voice and community stakeholders at the center of strategic planning with the most creative clinicians and scientists in the world.

A new grant will allow MUSC doctors and researchers to test several ideas for improving care and outreach to people with lupus or at risk of developing the autoimmune disease.

“I know our whole group is very excited,” said rheumatologist Gary Gilkeson, M.D., who serves as director of the MUSC Improving Minority Health in Rheumatic Diseases (IMHRD) Core Center for Clinical Research (CCCR). “When it came through we were thrilled.”

The two-year, $550,501 grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases includes three areas of concentration:

• The beginnings of an educational outreach effort on college campuses
• Piloting the use of a patient navigator for lupus patients at MUSC Health
• A partnership with the University of Alabama at Birmingham to increase understanding of minority health and health disparities among health care providers at both universities.

Lupus typically strikes women between the ages of 15 and 45 and is more common in black, Asian and Native American women. The body’s immune system turns on itself and begins attacking healthy cells, causing joint pain, fever, rashes, fatigue, swelling and sun sensitivity. Managing the disease is critical, because unchecked it can lead to serious complications like kidney failure.

But awareness of the disease, especially in the communities it most affects, lags.

“Some of the things I’ve heard from some of these young people is that this is an old white person’s disease or that it is a disease invented by scientists and hospitals to use them as guinea pigs,” said Edith Williams, Ph.D., who is heading up the educational outreach component.

She’s focusing her efforts on historically black colleges and universities (HBCUs) to try to reach the population at highest risk. Not only are black women more at risk for developing lupus, but they’re also more likely to be sicker, to be admitted to the hospital more often and to die from complications at higher rates, Williams said.

With this grant, she’ll work with focus groups at Claflin University, Voorhees College and South Carolina State University – as well as nonstudents ages 18 to 25 – to understand what young people already know about lupus and myths that are circulating about the disease. She will also determine the most effective way to reach out to them, whether that is flyers on a campus bulletin board, text blasts, postcards in the mail, digital messaging or messages from institutional leadership.

Williams understands why so many black people are skeptical of doctors and researchers, a distrust that stems from horrific research like the Tuskegee experiment.

“There is this very pervasive idea that the medical community is trying to use you, trying to use your body,” she said.

She hopes that her involvement, as an African American investigator, and the involvement of leaders at the HBCUs will encourage students to participate.

“Having a familiar, relatable face goes a long way, especially at this age,” she said.

Long term, she intends to use the insights gathered through the focus groups to develop educational outreach initiatives that could be used at all HBCUs in South Carolina and throughout the Southeast.

She hopes that as students learn about lupus and that such connective tissue diseases tend to run in families, they will share what they learn with their own families and friends.

Once diagnosed, managing lupus is a logistical challenge for many of the patients who Gilkeson and his colleagues see. About 2,000 people from across the state come to MUSC Health for lupus care, said Gilkeson. Many are from rural areas and have transportation problems. They might not be comfortable trying to navigate a big academic medical center. On top of that, their home communities might not have enough primary care doctors or might have lost the local hospital.

To help these patients, the grant allows for the hiring of a patient navigator to see if having such a person would reduce disease flares and hospital readmission rates.

This is something the lupus doctors have wanted to do for a long time but haven’t had the money for, Gilkeson said.

The patient navigator would become the point of contact for at-risk patients. The navigator would help those patients with transportation issues, make sure they’re getting their labs done and taking their medications and help them decide if their health concerns warrant a trip to the local emergency room or if they should see an MUSC rheumatologist.

Gilkeson said his group suspects the lack of primary care is helping to drive readmission rates. Some patients are in the hospital six or seven times a year. With a patient navigator to guide them, he hopes they can stave off Emergency Department visits for colds or sore throats and also catch and treat issues earlier so people don’t end up in the hospital.

“A lot of the readmissions could be prevented with intervention like this,” he said. “We’re really excited to see what the patient navigator can do.”

A new paper in Rheumatology, published by Oxford University Press, indicates that researchers have developed a new, easier, and more accurate tool to measure the progress of lupus in patients.

Systemic lupus erythematosus affects up to 1.5 million people in the United States and about one in 1000 people in the United Kingdom. The autoimmune disease causes the body’s immune system to attack its own healthy tissues, especially the joints, skin, and kidneys. Doctors need to measure the progress of the disease to make accurate decisions about treatment. Numerous studies have shown that keeping disease activity well controlled leads to less long-term organ damage. However, in a disease with so many different features this can be difficult to assess.

The standard tool used to measure disease progression, called the BILAG-2004 index, uses multiple reference documents including a case report form, a detailed glossary, and separate scoring algorithms covering nine different areas. This is often too difficult or time-consuming for doctors to complete during routine clinic visits,  particularly for those less familiar with the format. The challenges of the standard index can make it difficult for physicians to measure disease accurately and consistently. In clinical trials, the training required is long, mistakes in scoring are common, and physicians often express frustration with the method.

Researchers developed a new “Easy-BILAG” project to help doctors assess lupus using a simpler, faster tool. Easy-BILA, is a single-page document using color-coding to make assessment more user friendly way. The researchers found that, when compared across a variety of factors, the new tool enabled more accurate, consistent, and time efficient  measurements of lupus disease progression. Overall accuracy was boosted to 96% and general hospital rheumatologists could measure disease progression accurately in 91.3% of cases using the new tool, compared with only 75% when using the more difficult standard format. Rheumatologists were able to use the new tool to assess cases faster, in under an hour. The standard format took an average 80 minutes to complete.

Rheumatologists rated the new tool as intuitive and well adapted for routine clinical practice and expressed willingness to use it routinely. “The standard-format BILAG is useful for assessing individual patients,” said the paper’s author, Edward Vital, “but its downside was always the time and training needed to complete it. Being able to measure the progress of lupus quickly and easily has transformed my practice so I’m excited that we can now make it easy for anyone to do the same.”