As our knowledge in science/medicine is improving more and more pathologies such as advanced cancer, chronic infections, metabolic and auto-immune diseases are being characterized as associated with chronic inflammation in which one of the side effects is the down regulation of the ζ-chain expression associated with T & NK cells dysfunction leading to immunosuppression. Based on this phenomenon Imdrodia designs prognostic/diagnostic kits that will enable the monitoring of a patient’s immune system function
Inflammation is an essential immune response that enables combating infections or injury and maintains tissue homeostasis under a variety of noxious conditions. This response (known also as acute inflammation) promotes the optimal restoration of tissue structure and function, but must also rapidly turned off in order to prevent over reaction that could result in a irreversible damage. Failure to clear the endanger elements or inefficient termination of the response, could result in chronic inflammation. While acute (transient) inflammation is beneficial, chronic (sustained) inflammation is harmful and can cause suppression of the immune response. As for today, a large group of diseases are being characterized by chronic inflammation and ensuing immunosuppression. Loss of the immune system’s natural ability to defend the host leads to disease progression, patients become more vulnerable to opportunistic infections, irreversible tissue damage and unresponsiveness to a variety of immune-based treatments are detected. Currently, diagnosis of immunosuppressive conditions, in most cases, is done retrospectively. Therefore, there is an urgent need for objective, sensitive and reliable biomarkers that could sense the patient’s inflammatory and immunosuppressive state. Such measurements must be reproducible for frequently monitoring the patients’ immune system function, thus providing indication for the kind and therapy efficacies.
A biological molecule found in tissues, blood or other body fluids, that is a sign of a normal or abnormal process, or of a condition or disease. A biomarker can be used in order to check how well the body responds to a treatment for a disease or condition. Other terms such as molecular marker and signature molecule are sometimes being used to describe a biomarker.
Improdia possesses several biomarkers that sense the functionality of the immune function. These biomarkers are expressed in white blood cells and play different key roles in these cells that are mandatory for the execution of a normal immune response. Chronic inflammation affects the expression levels of these biomarkers, leading to their decreased expression. Treatments neutralizing the inflammatory response induce recovery to normal levels of the indicated biomarkers reflecting the recuperation of the patient’s immune system. Therefore, a simultaneous measurement of several biomarkers serves to cross validate the obtained results indicating the patients’ immune system function. Our leading biomarker is the CD247, which the proof of concept for its use is already well established and currently used in clinical studies. Another novel biomarker that we identified is the MBEI (temporary name) which is being characterized these days in first clinical studies. Additional biomarkers are in our pipeline and they will be released as additional validation studies are completed.
CD247 (also known as ζ-chain) is a protein expressed mainly in hematopoietic cells and serves as part of the T-cell’s main receptor and receptors expressed on NK cells. CD247 is a transmembrane molecule, has an extremely short extracellular domain of 9 amino acids and a long intracellular region composed of 113 amino acids, which enable the transmission of several signal-transduction pathways upon antigen recognition. CD247 plays a unique and vital role in T- and NK-cell activation and effector functions. Low CD247 expression levels result in impaired T- and NK-cell-mediated immune responses. We showed that a chronic inflammatory environment induces down-regulation of CD247 expression and impairment of T- and NK-cell functions, leading to suppression of the immune response.
MBEI is a protein expressed in many cell types including hematopoietic cells. MBEI contains several binding domains and in the past few years has been identified as an important protein participating in fundamental cellular activities such as plasma membrane receptors trafficking, internalization and degradation. We showed that inflammatory environment induces down-regulation of MBEI.