Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Suppressing immune system reverses otherwise untreatable case of blood disease

21.01.2003


Treatment with two medications that suppress the immune system, rituximab and cyclophosphamide, appears to have cured one woman of an otherwise untreatable case of the blood disease known as thrombotic thrombocytopenic purpura (TTP). The findings support the theory that TTP is an autoimmune disease, and not only provide insight into diagnosis and treatment, but also reveal clues about blood clotting and autoimmune diseases in general.



"In this particular patient who did not respond to standard therapy, immunosuppression seems to have been successful," says Morey A. Blinder, M.D., associate professor of medicine and of pathology and immunology at Washington University School of Medicine in St. Louis. "These results are promising for others suffering from similarly resistant cases of TTP."

Blinder led the study, in conjunction with J. Evan Sadler, M.D, Ph.D., professor of medicine and of biochemistry and molecular biophysics. Their findings appear in the Jan. 21 issue of the journal Annals of Internal Medicine.


TTP is a blood disorder that affects an estimated 3,000 Americans each year, most of whom are women of childbearing age. Prior to the early 1980s, the prognosis was grim: The risk of dying from complications of the disease such as heart attack or stroke was as high as 90 percent. And because the disease is so rare, it continues to be misdiagnosed and untreated.

Today, most patients who are diagnosed accurately with TTP are successfully treated with plasmapheresis, in which an individual’s blood is swapped for healthy blood in a daily process similar to dialysis for kidney failure. But plasmapheresis does not target the underlying problem, which is believed to be similar to autoimmune diseases such as lupus, in which the immune system attacks a person’s own tissues. Therefore, even with daily plasmapheresis, the disease returns in about 25 percent of patients.

In 2000, Sadler’s team, in collaboration with investigators at the University of Washington in Seattle, identified a protein in the bloodstream called von Willebrand factor-cleaving protease and found that it either is missing or abnormal in people with TTP, presumably as a result of disruption by the immune system. Without it, the protein called von Willebrand factor is not regulated and therefore sticks to itself, forming large clumps, or blood clots, that often lead to stroke or heart attack.

"The discovery of this protein really helps us understand the mechanism of blood clotting in general and how important von Willebrand factor is," says Blinder. "Also, we hope to use this knowledge to develop a definitive test for TTP so that it can be more easily diagnosed and more effectively treated. It also may be possible to genetically engineer the protein for infusion, similar to the use of insulin for diabetes."

To prevent the immune system from destroying or disrupting this essential cleaving protease, the Washington University team tested two drugs already shown to suppress the immune system. In October 2001, after 19 months of relapsing disease despite extensive plasmapheresis, the team gave one 42-year-old woman with severe TTP two drugs – rituximab and cyclophosphamide, both known anti-cancer drugs. Her symptoms and blood levels improved and continue to be stable to date.

"This may not be a public health issue like AIDS or breast cancer, but the fact that first this disease was almost always life-threatening and now may be curable is really important," says Blinder. "And now that we’re really beginning to understand the disease itself, it will help us diagnose and treat TTP and will provide insight into blood clotting and how immune diseases work in general."


###
Zheng X, Pallera AM, Goodnough LT, Sadler JE, Blinder MA. Remission of chronic thrombotic thrombocytopenic purpura after treatment with cyclophosphamide and rituximab. Annals of Internal Medicine, vol. 138, Jan. 21, 2003.

Funding from the National Institutes of Health and the Howard Hughes Medical Institute supported this research.

The full-time and volunteer faculty of Washington University School of Medicine are the physicians and surgeons of Barnes-Jewish and St. Louis Children’s hospitals. The School of Medicine is one of the leading medical research, teaching and patient-care institutions in the nation. Through its affiliations with Barnes-Jewish and St. Louis Children’s hospitals, the School of Medicine is linked to BJC HealthCare.

Gila Z. Reckess | EurekAlert!
Further information:
http://medinfo.wustl.edu/

More articles from Health and Medicine:

nachricht Laser activated gold pyramids could deliver drugs, DNA into cells without harm
24.03.2017 | Harvard John A. Paulson School of Engineering and Applied Sciences

nachricht What does congenital Zika syndrome look like?
24.03.2017 | University of California - San Diego

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

Im Focus: Researchers Imitate Molecular Crowding in Cells

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

Argon is not the 'dope' for metallic hydrogen

24.03.2017 | Materials Sciences

Astronomers find unexpected, dust-obscured star formation in distant galaxy

24.03.2017 | Physics and Astronomy

Gravitational wave kicks monster black hole out of galactic core

24.03.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>