Showing 4 ideas for tag "immune"

Goal 2: Reduce Human Disease

The role of Extracorporeal Photopheresis (ECP) in the prevention and treatment of rejection of heart and lung transplants

According to the ISHLT, more than 4,000 patients undergo a heart transplant each year, and almost 4,000 receive single or double lung transplants. Their prognosis depends heavily on the avoidance of rejection, which claims the majority of their lives. For heart transplant recipients, the median survival is 11 years, while for lung transplant recipients, it is approximately 5 years. The current most common anti-rejection... more »

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Compelling Question (CQ)

Details on the impact of addressing this CQ or CC

Patients who are fortunate to receive a matched heart or one or two lungs transplants are at high risk of dying from rejection early and even years after the operation. Thus, they are given cocktails of highly toxic anti-rejection drugs for the rest of their lives. Unfortunately, despite compliance with their drug regimens, many patients still suffer repeated episodes of rejection that may be fatal. In addition, they develop serious side-effects such as diabetes, infections, malignancies, renal failure, etc. ECP has been shown efficacy in preventing and treating cardiac transplant rejection, but the data are limited. ECP appears to benefit such patients by causing an increase in the number of circulating T regulatory (“T regs”) cells. T regs are known to mediate immune tolerance, the ultimate goal of a long-term successful transplant. The role of ECP in lung transplantation is mostly unknown. Very preliminary data have been gathered from retrospective studies. We suspect that patients with early bronchiolitis obliterans syndrome (“BOS”) will benefit from ECP prior to developing irreversible pulmonary damage. In both types of transplants, however, it is unknown when should ECP be started, how often it should be employed (treatment schedule), and for how long. Finally, the most compelling argument to use ECP in heart and lung transplantation is its excellent side-effect profile. Furthermore, ECP may allow a decrease in the number of drugs needed to prevent rejection.

Feasibility and challenges of addressing this CQ or CC

Many patients with heart and lung transplants develop severe and often fatal rejection despite the current drug options to prevent rejection. ECP could be added to their treatment regimens and decrease side-effects, improving long-term survival.

ECP is generally well tolerated and complications are extremely infrequent.

There is a great potential for multi-disciplinary collaboration between Apheresis Medicine, Cardiology, and Pulmonary specialists.

It is conceivable that manufacturers of ECP instruments will be interested in contributing to the design and support of these studies.

Such studies could shed light in the mechanism of action of ECP in heart and lung transplantation.

There is a need to develop standardized treatment regimens based on well designed clinical trials to further optimize the use of ECP. Development and standardization of measurable outcomes is critical for the success of clinical studies in apheresis in general, and ECP in particular.

Challenges:

  1. Limited number of institutions providing ECP treatment.
  2. Cost of ECP procedures.
  3. Small number of animal models available for apheresis research. Thus, limited studies of ECP mechanism(s) of action. However, understanding pathological mechanisms and their relationship to response to apheresis is critical for optimization and advancement of patient care in heart and lung transplantation.
  4. Lack of infra-structure for apheresis research.

Name of idea submitter and other team members who worked on this idea Marisa Marques on behalf of ASFA

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Goal 3: Advance Translational Research

Identification of autoantigens that elicit pathogenic immune responses in cardiovascular diseases

Pathogenic immune responses participate in the pathogenesis of many cardiovascular diseases. However, the autoantigens and foreign antigens that elicit the pathogenic immune responses have been poorly identified. Currently, the regulatory mechanisms on immune responses associated with diseases got some attentions. But, without detailed characterizations of this wide spectrum of autoantigens and foreign antigens in patients... more »

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Critical Challenge (CC)

Feasibility and challenges of addressing this CQ or CC
  1. use peptide/protein based microarray to antibody autoimmune responses associated with each major cardiovascular diseases;
  2. use MHC tetra-mers or similar techniques to characterize T cell autoimmune responses associated with each major cardiovascular diseases;
  3. determine autoantigen repertoire changes in patients' responses to current therapies, especially therapies with immune modulating effects;
  4. develop autoantigens-based immune therapies for clinical trials

Name of idea submitter and other team members who worked on this idea Professor Xiaofeng Yang, MD, PhD, Professor Hong Wang, MD, PhD, Professor Klaus Ley, MD

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2 down votes
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Goal 3: Advance Translational Research

Immune-Mediated hematologic disorders

What is the optimal approach to prevent and treat immune mediated hematologic disorders (autoimmune hemolytic anemia, immune thrombocytopenic purpura, etc) and complications of hematologic disease (inhibitors in hemophilia, transfusion-related alloimmunization, etc)

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Compelling Question (CQ)

Details on the impact of addressing this CQ or CC

Therapies for these disorders are suboptimal and current treatments are associated with significant side effects. Transfusion is limited by development of alloantibodies..

Feasibility and challenges of addressing this CQ or CC

NHLBI should support clinical trials in this area. Improved understanding of the biology and biomarkers predictive of disease development would aid in defining therapeutic approaches and trials.

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18 down votes
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Goal 2: Reduce Human Disease

Improving the Detection and Treatment of Cardiac Sarcoidosis

Sarcoidosis afflicts young adults, particularly African Americans and females, and often causes chronic disability or death. Cardiac sarcoidosis (CS) was once considered to be a rare disease manifestation; however, with the development of improved diagnostic testing procedures, such as MRI and PET scans, CS is now known to afflict up to 40% of sarcoidosis patients and is recognized as a major cause of death. The current... more »

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Critical Challenge (CC)

Details on the impact of addressing this CQ or CC

Improved detection of cardiac sarcoidosis (CS) is necessary to screen for CS in the sarcoidosis population and to identify those patients requiring further testing and personalized treatments. The optimal CS detection tool would be able to quantify the burden of cardiac disease, and would provide insight into disease activity (e.g., acutely active/reversible versus inactive/irreversible cardiac disease). Once validated, the CS detection tool would be used to risk stratify patients for the purpose of initial and subsequent treatments.

Feasibility and challenges of addressing this CQ or CC

Current and evolving imaging techniques have rapidly improved the detection of sarcoidosis, so these technologies are feasible. However, it is unclear how to interpret the results of these novel imaging techniques in the context of treating humans with sarcoidosis. A number of challenges remain (e.g., how to distinguish active from inactive cardiac sarcoidosis, and how to objectively assess disease severity as relates to the risk of serious adverse cardiac events). A strength of this project being that this field is poised for clinical investigations designed to improve cardiac sarcoidosis detection and treatment using existing technologies.

Name of idea submitter and other team members who worked on this idea Elliott Crouser, Subha Raman, Nabeel Hamzeh, Lisa Maier

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