July 11, 2019
The annual meeting of the Federation of Clinical Immunology Societies (FOCIS) is the key forum for translational immunology. The Lupus Research Alliance (LRA) is proud to co-sponsor this meeting, which allows researchers and clinicians to share knowledge across disease borders and to chart the path to the next major breakthroughs in disease treatment. At this year’s meeting, FOCIS 2019 in Boston, many researchers shared findings on topics that ranged from potential drug targets for lupus treatments to reasons why women and people of color are at more risk for the disease. Here are some of the lupus highlights of the meeting.
Exploring Possible Treatment Strategies
In an LRA-funded study that received a “Poster of Merit” ribbon, dermatologist Dr. Jillian Richmond at University of Massachusetts Medical School and colleagues found that patients with lupus produce proteins that pull immune cells into the skin by stimulating a molecule on the cells called CXCR3. Blocking CXCR3 in mice prevented the animals’ symptoms from getting worse. This, suggests that a like treatment might work in people.
Two studies by the National Institutes of Health’s Accelerating Medicines Partnership (AMP) focused on ways to avoid the surgical biopsies used to measure kidney damage and response to treatment. AMP is a public-private partnership between the NIH, pharmaceutical companies and non-profit groups such as the LRA. These results were published in Nature Immunology and reported recently by the LRA.
An LRA grantee for another project, University of Pittsburgh Assistant Professor of Rheumatology and Clinical Immunology Dr. Jeremy Tilstra teamed up with Dr. Mark Shlomchik, Endowed Professor and Chair of the Department of Immunology, and colleagues to test a new treatment approach in mouse models that develop lupus. They stopped the mice from making a key protein, MyD88, in some immune system cells and found that the animals’ lupus symptoms improved. The researchers conclude that targeting MyD88 or the molecules that switch it on may be an approach for lupus therapy.
Dr. Lieping Chen, a professor of cancer research and immunobiology at Yale University, and his team tested an immune checkpoint protein, PD-1H, that serves as an off switch for some immune cells. They found that flipping this switch in mouse models reduces lupus skin symptoms. Their work suggests that PD-1H is a key factor involved in lupus progression and that targeting it may work to treat lupus patients.
Finding the Immune System’s Mistakes
Research has shown that some T cells cause other immune cells to attack patients’ own tissues, while some T cells stop these attacks. Simone Caielli, Instructor in Pediatric Immunology at Weill Cornell Medicine; biostatistician Dr. Zhaohui Xu of the Baylor Research Institute; Dr. Jacques Banchereau, Director of Immunological Sciences at the Jackson Laboratory for Genomic Medicine; and Dr. Virginia Pascual, Director of the Drukier Institute for Children’s Health, found two molecular switches that cause T cells to become harmful or helpful. These findings have important implications for identifying novel drug targets. Dr. Pascual recently received the LRA’s prestigious Lupus Insight Prize.
Dr. Lea Simoni, a fellow in Dr. Michael Carroll ‘s lab at Boston Children’s Hospital and Harvard Medical School, and their colleagues may have found out why one version of a gene called C4 protects against lupus while a slightly different version of the gene does not. Patients who have the protective version C4A make a protein that is better at clearing up cellular junk that may trigger lupus.
Lupus shares some similarities with rheumatoid arthritis. To compare the diseases, Fan Zhang, Research Fellow in the lab of Harvard University Professor of Informatics Dr. Soumya Raychaudhuri, and a multidisciplinary team analyzed data from the Accelerating Medicines Partnership. They saw which genes were turned on in cells from people with lupus or rheumatoid arthritis. The researchers included experts in bioinformatics, rheumatology, immunology, genomics, genetics, molecular biology, biochemistry, biophysics, chemical biology, cell biology, and structural biology. They found that many of the same cells were involved in both diseases, but also saw difference molecules between cells from the two types of patients. These similarities and differences could help researchers identify treatments for the two diseases. This project is part of the NIH Accelerating Medicines Partnership, which is co-funded by the LRA.
Investigating Lupus Risk
Two studies may help researchers better grasp the role of the protein SRSF1 in controlling immune cells called T cells in lupus. The team included LRA Scientific Advisory Board member Dr. George Tsokos, Professor of Rheumatology and Immunology at Harvard Medical School, lead investigator Dr. Vaishali Moulton and other colleagues. Their work showed that mouse T cells that lack SRSF1 release more molecules that drive inflammation and cause lupus symptoms. The results found that SRSF1 regulates T cell activation. T cells from patients with lupus make less SRSF1 than normal, which may let the cells switch on and turn harmful. Another study by Dr. Moulton’s group with Research Assistant Melissa Carr-Reynolds of Harvard Medical School as the lead author found that the female hormone estrogen helps adjust the amount of SRSF1 in T cells. That may be one reason why lupus is much more common in women than in men.
Results presented by Dr. Samantha Slight-Webb, a member of Dr. Joel Guthridge’s lab at the Oklahoma Medical Research Foundation, and colleagues in rheumatology and immunology may explain why African-Americans are at higher risk for lupus and often have more severe symptoms. Certain immune cells that trigger damage to tissues and organs are more common in African-Americans, and some of the molecular controls of their immune cells are more likely to malfunction.
Many of the scientists who presented at FOCIS 2019 have made a major impact in other fields of research. The results these researchers shared show how crossing boundaries between scientific fields can lead to important discoveries in lupus.