Novel Use Of Mass Spectrometry Help Improve TTP Patient Outcomes

The development of a rapid and accurate assay for a life-threatening disorder relies on a novel use of mass spectrometry and proteinChip arrays.

In an article in the current issue of Spectroscopy, researchers at the Ohio State University College of Medicine and Public Health describe the clinical evaluation of thrombotic thrombocytopenic purpura (TTP) using Surface Enhanced Laser Desorption/Ionization Time of Flight (SELDI-TOF) mass spectrometry.TTP is a condition caused by a deficiency in a metalloproteinase called ADAMTS13. With a timely diagnosis, TTP patients usually respond to plasma exchange therapy. However, many patients relapse after therapy. Thus, there is a need for both a rapid diagnostic test to help clinicians start therapy and for a biomarker that can anticipate recurrence.Without enough ADAMTS13, extensive blood clots may occur throughout the body and can cause death. ADAMTS13 prevents this by breaking apart another protein that causes the clotting process. By measuring one of the broken fragments using SELDI-TOF, the researchers found that they could determine ADAMTS13 activity levels in the patient's blood.SELDI-TOF mass spectrometry offers an unique property to specifically capture and concentrate the target protein in a binding array. Afterwards it becomes relatively simple to measure the analyte. In this application, an immobilized metal affinity capture (IMAC) array was chosen which could bind to a product of ADAMTS13 proteolysis, ahistidine-containing fragment. The product was then measured by the mass spectrometer. Thus, the method was used to evaluate ADAMTS13 activity in TTP patients.Writing in the article, Haifeng M. Wu, MD, states "Since the implementation of our SELDI-TOF based method, fast turnaround time for the detection of ADAMTS13 activity has greatly helped us in making the correct diagnosis, instituting appropriate therapy, and improving patient outcomes."(Source: Ohio State University : January 2007.)