Researchers from the University of North Carolina provide an explanation for why patients with an aggressive form of vasculitis caused by anti-neutrophil cytoplasmic autoantibodies (ANCAs) against PR3 protein are at a high risk of developing blood clots. They found that these patients have complementary antibodies that work against plasminogen, which plays an important role in blood coagulation.
Although further development is needed on the assay test used in this study, antibodies against plasminogen could serve as a marker for patients at an increased risk of developing blood clots.
The study followed patients being treated with a plasma exchange therapy, which removes the PR3 ANCAs from the blood. Previous studies have suggested that antibodies to complementary proteins may play an important role in the initiation of autoimmune diseases.
“Using an antibody reactive with complementary PR3 protein, prod-uced in the laboratory, we analyzed protein pools removed from the patients' plasma during plasma exchange therapy to identify any existing proteins that were reactive with the anti-complementary PR3 antibody,” Dr. Falk explains.
The results showed autoantibodies to a complementary protein that, to the researchers' surprise, turned out to be plasminogena protein. In the research, 22% of the patients with PR3 ANCA vasculitis had antiplasminogen antibodies. Of these patients, 56% had serious blood-clotting problems as a complication to their disease.
“Identification of potentially pathogenic anti-plasminogen antibodies provides an explanation of why patients with PR3-ANCA disease have a high incidence of blood clots,” Dr. Falk notes.
Dr. Falk also points out that 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.” 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.
The findings are published online in the Journal of the American Society of Nephrology (JASN) and will appear in the December print issue.