 |
|
Protein complementarity may offer new insights into autoimmune diseases
August 14, 2008Antibodies against plasminogen linked to blood clots in patients with ANCA vasculitis
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.
American Society of Nephrology
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.
American Society of Nephrology
Autoimmune Disease Current Events and Autoimmune Disease News RSSResearcher tricks immune system in diabetic mice
The body's immune system hates strangers. When its security patrol spots a foreign cell, it annihilates it.
Lung airway cells activate vitamin D and increase immune response
Vitamin D is essential to good health but needs to be activated to function properly in the human body. Until recently, this activation was thought to happen primarily in the kidneys, but a new University of Iowa study finds that the activation step can also occur in lung airway cells.
Type-1 diabetes not so much bad genes as good genes behaving badly, Stanford research shows
Investigators combing the genome in the hope of finding genetic variants responsible for triggering early-onset diabetes may be looking in the wrong place, new research at the Stanford University School of Medicine suggests.
Toxic Bile Damages the Liver
Researchers at the Heidelberg University Hospital have discovered a new genetic disease that can lead to severe liver damage. Because a protective component of the bile is missing, the liver cells are exposed to the toxic components of the bile, resulting in cirrhosis of liver, a transformation of liver cells into connective tissue with a gradual loss of liver function.
A reversal of thinking: How women with lupus can increase chance for healthy pregnancies
In the not so distant past, women with systemic lupus erythematosus (SLE), an autoimmune disease, were advised not to have children, and if they became pregnant, to have therapeutic abortions to prevent severe flares of their lupus.
First international guidelines for treatment of psoriatic arthritis
Rheumatologists, dermatologists, and patient advocates have come together to publish the first-ever international guidelines for the treatment of psoriatic arthritis, a disease that mainly affects people who have psoriasis but also some people without it.
Green tea may delay onset of type 1 diabetes
A powerful antioxidant in green tea may prevent or delay the onset of type 1 diabetes, Medical College of Georgia researchers say.
New hope for multiple sclerosis sufferers
A drug which was developed in Cambridge and initially designed to treat a form of leukaemia has also proven effective against combating the debilitating neurological disease multiple sclerosis (MS).
New mechanism for cardiac arrhythmia discovered
It has long been thought that virus infections can cause cardiac arrhythmia. But why has not been understood. Ulrike Lisewski, Dr. Yu Shi, Michael Radke and Professor Michael Gotthardt of the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch, Germany, have now discovered the molecular mechanism.
Survival instincts propel 'difficult patient' to insist on quality care
Michelle Mayer had to become a "difficult patient" before she could get her physicians to accurately diagnose the disease that was destroying her health.
More Autoimmune Disease Current Events and Autoimmune Disease News Articles
 | Living Well with Autoimmune Disease: What Your Doctor Doesn't Tell You...That You Need to Know by Mary J. Shomon A complete guide to understanding the mysterious and often difficult-to-pinpoint disorders of the immune system--and finding the keys to diagnosis, treatment, and recovery. An estimated fifty million people suffer from symptoms including fatigue, joint pains, depression, or heart palpitations — signs that the immune system has turned on itself, causing conditions such as thyroid disease,... |
 | Women, Work, and Autoimmune Disease: Keep Working, Girlfriend! by Rosalind Joffe, Joan Friedlander When a woman receives a life-changing diagnosis of a serious, chronic illness, her first instinct may be to quit the workforce. This may bring a strong sense of relief initially, but as her disease becomes manageable, work is again desirable. Women, Work, and Autoimmune Disease urges women so affected to stay employed in order to preserve their independence and sense of self. Filled with tips,... |
 | The Autoimmune Epidemic: Bodies Gone Haywire in a World Out of Balance--and the Cutting-Edge Science that Promises Hope by Donna Jackson Nakazawa From the foreword by Dr. Douglas Kerr, Director, Johns Hopkins Transverse Myelitis Center "The Autoimmune Epidemic by Donna Jackson Nakazawa is an astounding book....It is the kind of book that will rivet you and scare you. It will make you angry. It will amaze you with the courage of some of the people described in the book...The Autoimmune Epidemic is every bit as compelling as Upton Sinclair's... |
 | What Your Doctor May Not Tell You About Autoimmune Disorders: The Revolutionary, Drug-Free Treatments for Thyroid Disease, Lupus, MS, IBD, Chronic Fatigue; Rheumatoid Arthritis, and Other Diseases by Stephen B. Edelson, Deborah Mitchell Autoimmune disorders are not well understood and can be difficult to treat. The result is that there are millions of people with autoimmune diseases looking for answers, relief and healing, and not finding them. The majority of doctors treating autoimmunity simply attack the symptoms and treat each disorder separately, but Dr Edelson believes all autoimmune disorders are similar at their core and... |
 | Women and Autoimmune Disease: The Mysterious Ways Your Body Betrays Itself by Robert G. Lahita, Ina L. Yalof A cutting-edge examination of the mysterious world of autoimmune disease—and the new discoveries made daily that may save women's lives Autoimmune diseases—including chronic fatigue syndrome, vasculitis, juvenile diabetes, alopecia, Graves' disease, Sjogren's syndrome, lupus, rheumatoid arthritis, and multiple sclerosis—are among the most devastating conditions afflicting women today and... |
 | The Autoimmune Diseases, Fourth Edition Since publication of the Third Edition in 1998, the understanding of the immune mechanisms underlying autoimmunity and autoimmune disease has significantly deepened and broadened. This Fourth Edition incorporates new material and combines common themes underlying inductive and effector mechanisms and therapies that relate generally to the autoimmune disorders. It discusses the biological basis of... |
 | The Autoimmune Connection by Rita Baron-Faust, Jill P. Buyon As featured in the New York Times and recommended by the National Women's Health Resource Center and the Society for Women's Health Research, The Autoimmune Connection discusses the links between autoimmune diseases and offers up-to-date information on diagnosis, treatments, and risks for women with one or more autoimmune disease, such as lupus, rheumatoid arthritis, or Crohn's... |
 | Diagnostic Criteria in Autoimmune Diseases According to the Autoimmune Diseases Coordinating Committee (ADCC), between 14.7 and 23.5 million people in the USA – up to eight percent of the population are affected by autoimmune disease. Autoimmune diseases are a family of more than 100 chronic, and often disabling, illnesses that develop when underlying defects in the immune system lead the body to attack its own organs, tissues, and... |
 | Bible Cure for Autoimmune Disorders (Bible Cure (Siloam)) by Don Colbert |
 | Thriving With Your Autoimmune Disorder: A Woman's Mind-Body Guide by Simone Ravicz Ph.D. M.B.A. Women facing chronic pain and illness due to multiple sclerosis, rheumatoid arthritis, chronic fatigue, and other autoimmune disorders have a new place to look for encouragement. In this comprehensive and caring guide, Simone Ravicz presents a wide range of suggestions for not merely enduring illness but finding ways to thrive in spite of it. Ravicz herself suffers from autoimmune disorders. As... |
| © 2008 BrightSurf.com |