Proteomic Signatures of GVHD

Hematopoietic Stem Cell Transplantation (HSCT) is the only curative treatment for many hematologic diseases, with curative potential due to a well-established Graft-Versus-Leukemia (GVL) effect. Unfortunately, despite decades of HSCT success, the Graft Versus Host Disease (GVHD) remains the major determinant of non-relapse mortality of transplant recipients. GVHD onset is generally anticipated by the degree of mismatch in the major histocompatibility complex (MHC) between donors and recipients. However, despite receiving fully matched grafts from siblings or unrelated donors, a fair proportion of patients still develop GVHD.

Finding a robust, non-invasive diagnostic biomarker to predict GVHD development and/or severity at early stages post-transplant would be beneficial for patients to help tailoring the appropriate prophylaxis and avoid undesirable outcome. Bio-fluids such as urine, saliva and sweat, are commonly used for the diagnosis of some diseases. Sweat, for instance, is normally used for the diagnosis of cystic fibrosis by measuring its chloride content. Proteomic profiles have been extensively investigated as a prediction/diagnosis tool for a variety of diseases. The protein profile of sweat has been recently used to determine active tuberculosis (TB). Sweat can be induced using electric pulses. Sweat test is a procedure used commonly in the clinic as a diagnostic tool for cystic fibrosis (CF). The procedure is relatively easy, non-invasive and takes approximately 30-45 minute to induce sweat. In addition, sweat is relatively cleaner than other bio-fluids such as saliva and urine which require less pre-preparation.

We here propose to prospectively investigate the protein content in the sweat of patients receiving HSCT at different time points before and after transplantation. The major goal of this proposal is to find a biomarker to correlate the protein profiling of sweat with the outcome of the transplant in an attempt to predict GVHD in addition to the other transplant-related detrimental complications post-HSCT. Ultimately, this will significantly improve the diagnosis and treatment of HSCT recipients.