Protein complementarity may offer new insights into autoimmune diseases

Aug 13, 2008

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 researchers looked for complementary proteins in a group of patients with a rare autoimmune disease called ANCA vasculitis. People with autoimmune diseases have abnormal "autoantibodies" that cause the immune system to attack the body's own cells and tissues. In patients with ANCA vasculitis, the ANCAs attack a type of white blood cells called neutrophils, which in turn attack the blood vessel walls. The resulting blood vessel inflammation (vasculitis) can lead to kidney damage (glomerulonephritis) and other complications.

The patients in the study had a particularly aggressive form of vasculitis caused by ANCAs against a protein called PR3. They were being treated with a procedure called plasma exchange therapy (or plasmapheresis), which removes the PR3 ANCAs from the blood. "Using an antibody reactive with complementary PR3 protein, produced 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. Previous studies have suggested that antibodies to complementary proteins may play an important role in the initiation of autoimmune diseases.

The results showed autoantibodies to a complementary protein that, to the researchers' surprise, turned out to be plasminogen—a protein that plays a key role in blood clotting. 22% of the patients with PR3 ANCA vasculitis had anti-plasminogen antibodies, including 56% of those who had serious blood-clotting problems as a complication of their disease. "Identification of potentially pathogenic [disease-causing] anti-plasminogen antibodies provides an explanation of why patients with PR3-ANCA disease have a high incidence of blood clots," says Dr. Falk.

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.

Source: American Society of Nephrology

Explore further: Aid group: No need to isolate staff treating Ebola

add to favorites email to friend print save as pdf

Related Stories

Final pieces to the circadian clock puzzle found

Sep 14, 2014

Researchers at the UNC School of Medicine have discovered how two genes – Period and Cryptochrome – keep the circadian clocks in all human cells in time and in proper rhythm with the 24-hour day, as well ...

The 'yin and yang' of malaria parasite development

Jul 09, 2014

Scientists searching for new drug and vaccine targets to stop transmission of one of the world's deadliest diseases believe they are closer than ever to disrupting the life-cycle of this highly efficient ...

Recommended for you

Aid group: No need to isolate staff treating Ebola

18 minutes ago

Doctors Without Borders insisted Friday, after one of its doctors who worked in Guinea came down with Ebola in New York, that quarantines of health workers returning from the hot zone are not necessary when ...

New York on alert over first Ebola case

27 minutes ago

New York went on alert Friday as authorities sought to calm fears among the city's 8.4 million residents after a doctor tested positive for Ebola.

Volunteer guidelines for clinicians in the Ebola epidemic

1 hour ago

Disaster Medicine and Public Health Preparedness Journal has released a novel, informative article that speaks to volunteers within the Ebola epidemic. The article, contributed by a consortium of Boston-based hospitals, is ent ...

US lawmaker: New case raises questions on Ebola

2 hours ago

The new case of Ebola diagnosed in New York City has raised "even more questions about procedures in treating patients and risks to Americans," a Republican committee chairman said Friday.

User comments : 0