Scientists have long suspected that immune system cells called neutrophils play a role in lupus, a disease that occurs when the body’s immune system attacks and damages its own tissues, including the skin, joints, heart, lungs, kidneys and brain. More than a half-century ago, scientists found that the blood serum from patients with lupus triggered alterations in the nuclei of these abundant immune system cells. This finding was used to diagnose patients with lupus for many years, but the role of neutrophils in the disease remained elusive. Scientists supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) have now found a new role for these cells in lupus. Their discovery, published in the journal Science Translational Medicine, could potentially lead to the identification of new therapeutic targets for the disease.
Following the discovery of an abnormal neutrophil gene expression pattern in the blood of children with lupus, Virginia Pascual, M.D., and her colleagues at the Baylor Institute for Immunology Research found that exposing neutrophils from children with lupus to anti- ribonucleoprotein (anti-RNP) autoantibodies (a type of antibody commonly made by people with lupus) caused the neutrophils to die rapidly, similar to the way neutrophils from healthy children die in response to bacterial and fungal infections. But, perhaps more importantly, they found that in the process of dying, the neutrophils from children with lupus released material from cell nuclei, which did not happen with the neutrophils of healthy children exposed to the same autoantibodies. The release of this material led to the activation of other immune system cells, particularly those that produce interferon-alpha (IFN-?), one of a family of potent immune proteins. Earlier research by Dr. Pascual and her colleagues showed IFN-? to be highly elevated in patients with lupus, and likely to be involved in the immune system alteration and damage in the disease.
The scientists hope that recognizing and better understanding the process of neutrophil death, and the subsequent immune cell activation, will lead to the identification of targets to block this type of cell death and intervene in the process that ultimately leads to tissue damage in lupus.
The mission of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), a part of the U.S. Department of Health and Human Services’ National Institutes of Health (NIH), is to support research into the causes, treatment, and prevention of arthritis and musculoskeletal and skin diseases; the training of basic and clinical scientists to carry out this research; and the dissemination of information on research progress in these diseases. For more information about NIAMS, call the information clearinghouse at (301) 495-4484 or (877) 22-NIAMS (free call) or visit the NIAMS website at http://www.niams.nih.gov.
Garcia-Romo GS, Caielli S, Vega B, Connolly J, Allantaz F, Xu Z, Punaro M, Baisch J, Guiducci C, Coffman RL, Barrat FJ, Banchereau J, Pascual V. Netting neutrophils are major inducers of type I IFN production in pediatric systemic lupus erythematosus. Sci Transl Med. 2011 Mar 9; 3(73):73ra20. PubMed PMID: 21389264.