In the autoimmune disease systemic lupus erythematosus or SLE, the immune system produces antibodies against parts of the body itself. How cells that produce those antibodies escape the normal “checks and balances” has been unclear, but recent research from Emory University School of Medicine provides information about a missing link.
Investigators led by Ignacio (Iñaki) Sanz, MD, studied blood samples from 90 people living with SLE, focusing on a particular type of B cells. These “DN2” B cells are relatively scarce in healthy people but substantially increased in people with SLE.
The results were published in the journal Immunity.
People with lupus can experience a variety of symptoms, such as fatigue, joint pain, skin rashes and kidney problems. Levels of the DN2 cells were higher in people with more severe disease or kidney problems. DN2 B cells are thought to be “extra-follicular,” which means they are outside the B cell follicles, regions of the lymph nodes where B cells are activated in an immune response.
“Overall, our model is that a lot of lupus auto-antibodies come from a continuous churning out of new responses,” says postdoctoral fellow Scott Jenks, PhD, co-first author of the paper. “There is good evidence that DN2 cells are part of the early B cell activation pathway happening outside B cells’ normal homes in lymph nodes.”
Previous research at Emory has shown that African American women have significantly higher rates of lupus than white women. In the current study, the researchers observed that the frequency of DN2 cells was greater in African American patients. Participants in the study were recruited by Emory, University of Rochester and Johns Hopkins. Read more
People with systemic lupus erythematosus can experience a variety of symptoms, such as fatigue, joint pain, skin rashes and kidney problems. Often the symptoms come and go in episodes called flares. In lupus, the immune system goes haywire and produces antibodies that are directed against the body itself.
A team of Emory scientists has been investigating some fundamental questions about lupus: where do the cells that produce the self-reactive antibodies come from? Are they all the same?
In the accompanying video, Kelli Williams, who helps study the disease and has lupus herself, describes what a flare feels like. In addition, Emory researchers IÃ±aki Sanz, MD and Chris Tipton, PhD explain their findings, which were published this summer inÂ Nature Immunology.
Judging by the number and breadth ofÂ abstractsÂ on lupus at the Department of Medicine Research DayÂ (where Tipton won 1st place for basic science poster),Â more intriguing findings are in the pipeline. Goofy Star Wars metaphors and more explanations of the scienceÂ here.
Emory immunologistsÂ have identified corresponding cells in which long-lived antibody production resides. A subset of plasma cells keep a catalog of how an adultâ€™s immune system responded to infections decades ago, in childhood encounters with measles or mumps viruses.
The results, published Tuesday, July 14 inÂ Immunity, could provide vaccine designers with a goalpost when aiming for long-lasting antibody production.
â€œIf youâ€™re developing a vaccine, you want to fill up this compartment with cells that respond to your target antigen,â€ says co-senior author F. Eun-Hyung Lee, MD, assistant professor of medicine at Emory University School of Medicine and director of Emory Healthcareâ€™s Asthma, Allergy and Immunology program.
The findings could advance investigation of autoimmune diseases such as lupus erythematosus or rheumatoid arthritis, by better defining the cells that produce auto-reactive antibodies.
Lee says that her team’s research on plasma cells in humansÂ provided insights unavailable from mice, since mice don’t live as long and their plasma cellsÂ also have a different patternÂ of protein markers.Â More here.