The discovery of "complementary" antibodies against plasminogen in patients with blood vessel inflammation caused by anti-neutrophil cytoplasmic autoantibodies (ANCAs) may lead to new approaches to research, testing, and treatment of ANCA vasculitis and other autoimmune diseases, suggests a paper in the December Journal of the American Society of Nephrology (JASN).
"This research is especially important because it opens new avenues for exploration of autoimmune disease that embrace the concepts of protein complementarity," comments Ronald J. Falk, MD, of UNC Kidney Center, University of North Carolina, Chapel Hill, one of the authors of the study. "The power of this approach has gone unappreciated, even though the basic ideas of protein complementarity have been proven in other settings over the years."
The results may have important implications for the care of patients with ANCA vasculitis most immediately, in identifying those at high risk of developing blood clots. However, the assay used in the study was inadequate for clinical use. "What is needed is a clinical test that is specific and precise enough to measure anti-plasminogen antibody levels," adds Dr. Falk. Further studies will be needed to establish the clinical value of such a test, including the correlation between complementary antibody levels and the risk of blood clots.
In addition, the study suggests that complementary antibodies may play a more important role in autoimmune diseases than scientists have previously realized. The methods used may lead to the discovery of autoantibodies to complementary proteins in other autoimmune diseases for example, rheumatoid arthritis or multiple sclerosis. "Hopefully, our discoveries will entice scientists to consider the potential implications of protein complementarity," says Dr. Falk.
This research was supported by National Institutes of Health grant 2P01 DK058335.
The article, entitled "Antibodies with Dual Reactivity to Plasminogen and Complementary PR3 in PR3-ANCA Vasculitis," will appear online at http://jasn.asnjournals.org on Wednesday, August 13, 2008, and in the December 2008 print issue of JASN.