A hypothesis on the molecular underpinnings of lupus has been turned on its head in a new Yale study. Lupus is characterized by attacks on the DNA and RNA of normal cells by the immune system, but researchers have struggled to understand the source of the antibodies against the genetic material.
One theory is based on the everyday destruction of neutrophils, the most abundant type of white blood cell. When neutrophils undergo a particular kind of cell death, their DNA is packaged into a neutrophil extracellular trap (NET) and released. Scientists have suspected that an accumulation of NETs could stimulate the formation of antibodies against DNA.
Mark J. Shlomchik, M.D., Ph.D., professor of laboratory medicine and immunobiology, and colleagues tested this theory by crossing mice that cannot form NETs with mice prone to lupus: if the theory were correct, such mice would be less likely to develop full-blown lupus. Instead, the mice had more severe lupus, with a different pattern of autoantibodies. The results, published October 24 in Science Translational Medicine, suggest that neutrophils may be important sources of immune-system stimulation in lupus, but that NETs could play a protective, rather than aggravating, role.