Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is a rare but devastating autoimmune disease affecting the blood vessels. In this disease, antibodies attack immune cells called neutrophils, causing inflammation in small- to medium-sized blood vessels. This in turn leads to organ damage, particularly in the airways, lungs, and kidneys, and to recurring symptoms such as fever, fatigue, and bleeding in the lungs. Treatment usually consists of a three- to six-month course of cyclophosphamide—which suppresses immune cells known as B cells that produce the self-destructive antibodies—followed by long-term daily use of other immune-suppressing drugs plus steroids.
Before the cyclophosphamide-based treatment was developed by NIAID investigators in the 1970s, approximately 80 percent of people with ANCA-associated vasculitis died within two years of disease onset. While the drug has been a lifesaver, its long-term use puts patients at increased risk of infection, cancer, and infertility.
In a recent study, NIAID-supported researchers evaluated a new treatment strategy based on the drug rituximab, a synthetic antibody that selectively reduces the number of circulating B cells. The researchers found that rituximab provided the same benefits as cyclophosphamide but required a shorter course of treatment. Early results also suggest that people with relapsing disease respond better to rituximab than cyclophosphamide. In the trial, 67 percent of the people given rituximab were able to stop all steroid use, compared with only 42 percent of those given standard care.
Stone JH, Merkel PA, Spiera R, Seo P, Langford CA, Hoffman GS, Kallenberg CG, St Clair EW, Turkiewicz A, Tchao NK, Webber L, Ding L, Sejismundo LP, Mieras K, Weitzenkamp D, Ikle D, Seyfert-Margolis V, Mueller M, Brunetta P, Allen NB, Fervenza FC, Geetha D, Keogh KA, Kissin EY, Monach PA, Peikert T, Stegeman C, Ytterberg SR, Specks U; RAVE-ITN Research Group. Rituximab versus cylophosphamide for ANCA-associated vasculitis. N Engl J Med. 2010 Jul 15;363(3):221-32.
Primary immune deficiency diseases (PIDDs) are caused by inherited defects in specific cells of the immune system. People with PIDDs generally have an increased susceptibility to infections and may have other medical problems that include autoimmune diseases, weakened lung function, tumors, and failure to thrive.
National Institutes of Health (NIH) investigators have found a genetic mutation that accounts for a previously unidentified immune disease in 11 patients receiving treatment in the NIAID Primary Immune Deficiency Clinic. While the patients received care for their symptoms—including persistent skin infections, acute allergies, and cancer—investigators observed that they all had a mutation in the same gene, DOCK8. The normal function of DOCK8 is unknown. But the people with DOCK8 mutations had fewer anti-virus immune cells, fewer antibody-producing cells, and increased numbers of white blood cells associated with allergy, suggesting that DOCK8 is essential for protection against viruses and for the development of allergies and cancers.
Although more study is needed to determine if DOCK8 mutations occur in other people with similar symptoms, DOCK8 immunodeficiency syndrome may be a new PIDD. Identifying a cause for the disease has provided comfort to some of those diagnosed who had battled an unknown immune disease for years.
Zhang Q, Davis JC, Lamborn IT, Freeman AF, Jing H, Favreau AJ, Matthews HF, Davis J, Turner ML, Uzel G, Holland SM, Su HC. Combined immunodeficiency associated with DOCK8 mutations. N Engl J Med. 2009 Nov 19;361(21):2046-55.
Last Updated December 21, 2011
Last Reviewed June 03, 2011