Four-year, $2.5 Million Study Could Directly Benefit Patients with Sickle Cell Disease
New York, NY., August 11, 2014. For patients with sickle cell disease (SCD), blood transfusions remain a cornerstone of treatment, with 60-90% of patients receiving red blood cell (RBC) transfusions in their lifetime. Despite provision of extended antigen-matched donor RBCs, as many as two-thirds of the patients continue to develop antibodies against polymorphic antigens on donor cells, termed alloimmunization that can cause the rejection of the transfused cells and potential life- threatening complications. Identification of biomarkers of alloimmunization in this patient population is therefore of great interest and will help to identify in advance patients most likely to make antibodies in response to transfusion.
“We believe that these individuals (who develop antibodies) have certain hyperactive immune cells,” said Dr. Karina Yazdanbakhsh of New York Blood Center’s Laboratory of Complement Biology. “Our goal is to identify these cells and understand what makes them hyperactive. This knowledge will help us to pre-screen for SCD patients who are likely to reject transfusions. It will also create a strong foundation for development of treatments to cure their hyperactive immune system.”
The $2.5 million, four-year grant from the National Institute of Health’s (NIH) National Heart, Lung and Blood Institute includes a subcontract with the Children’s Hospital of Philadelphia.
Genetic as well as acquired patient-related factors are likely to influence the process of alloimmunization. Dr. Yazdanbakhsh and her colleagues recently reported altered regulatory T cells (Tregs) which normally suppress pathogenic immune response in chronically transfused SCD antibody producers as compared to SCD non-producers. They have further identified lower levels of heme oxygenase I (HO-1), known for its anti-inflammatory and immunosuppressive role, in monocytes from alloimmunized SCD patients and altered monocyte control of Treg development in response to hemin, a surrogate marker for transfused RBC breakdown products. With the newly funded NIH grant support, Dr. Yazdanbakhsh’s laboratory will test the hypothesis that inadequate levels/activity of HO-1 alters the anti- inflammatory state of the innate immune cells of SCD patients following RBC transfusion, resulting in altered balance of Tregs and pathogenic T cell responses against RBCs that favor alloimmunization.
“We believe that a detailed mechanistic understanding of the ways in which innate immune abnormalities can contribute to pathogenic T cell responses in alloimmunized SCD patients will help future identification of biomarkers of alloimmunization with the goal that this information will ultimately help guide therapy in these patients,” concluded Dr. Yazdanbakhsh.
About Lindsley F. Kimball Research Institute: Since 1964, LFKRI has led the way in blood research, breaking new ground in transfusion medicine and disease treatment and prevention. The institute is committed to furthering research efforts that support the discovery of new blood-related products, techniques, and therapies. LFKRI's work has dramatically impacted global health, improved blood banking, nurtured a generation of scientists, and added significantly to the world's store of biomedical knowledge. From the beginning, LFKRI has supported basic research to understand blood and disease at the molecular level as well as translational research that transforms the findings into major breakthroughs. With 17 state-of-the-art laboratories and close to 100 researchers, LFKRI brings world-class research to life every day. For further information, visit http://nybloodcenter.org/research/kimball-research-institute/.
About New York Blood Center: New York Blood Center (NYBC) is one of the nation's largest non-profit, community-based blood centers. For 50 years, NYBC has been providing blood, transfusion products and services to hospitals serving more than 20 million people in New York City, Long Island, the HudsonValley, New Jersey, and parts of Connecticut and Pennsylvania. NYBC is also home to the Lindsley F. Kimball Research Institute and the National Cord Blood Program, the world's largest public cord blood bank. NYBC provides medical services and programs (Clinical, Transfusion, and Hemophilia Services) through our medical professionals along with consultative services in transfusion medicine. Please visit us on Facebook at www.Facebook.com/newyorkbloodcenter. Follow us on Twitter: @NY_BloodCenter. Website: www.nybloodcenter.org.