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The field of rheumatology took center stage when a handful of speakers discussed trends and research during a disease-oriented session of the 2015 Federation of Clinical Immunity Societies (FOCIS 2015) conference held in San Diego in June.
Neutrophils in SLE
Mariana Kaplan, MD, chief of Systemic Autoimmunity Branch at the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), spoke about the role of neutrophils in systemic lupus erythematosus (SLE) and other autoimmune diseases.
In the past couple of years, an effort has been made to define neutrophils as an “important shaper of the immunological landscape,” Dr. Kaplan said. Her recent research has concentrated on neutrophil extracellular traps (NETs), which in lupus may serve to amplify disease by activating inflammation.
Lupus is an autoimmune syndrome that affects mostly young women and is characterized by profound clinical heterogeneity, noted Dr. Kaplan.
Dr. Kaplan
“It is considered one of the big imitators in the clinic, because lupus can really present in so many different ways,” she said. “The disease is typically characterized by episodes of flares and remissions, and it is this smoldering disease and periods of flares we think that significantly contribute to morbidity and mortality in the long term.”
Most patients with lupus require chronic use of immunosuppressant drugs. Although the survival rate has improved compared with the latter half of the past century, the standard mortality rate for lupus is still significantly higher than in the general population, Dr. Kaplan said (also see “SLE: Why Race Still Matters”).
“We know that lupus patients have a striking increase in their risk of developing cardiovascular diseases, such as myocardial infarction and stroke, and it’s quite likely that it is the immune dysregulation characteristic of lupus that is driving this enhanced risk.”
A significant proportion of lupus patients have increased production of type 1 interferons, which mediate the disease and likely play an important role in promoting abnormalities and end complications like cardiovascular disease. Some of the answers to what feeds this interferon production appear to be tied to neutrophils produced in bone marrow. In the past, neutrophils have been somewhat ignored because they die so fast, are hard to manipulate and the short life span makes them difficult to study, Dr. Kaplan said.
“So we have proposed that perhaps how neutrophils die may be particularly important in the context of autoimmunity, because as we all know neutrophils are the most abundant white blood cell.”
