Clinical Research Directory

Acalabrutinib Maleate and Bortezomib for Patients With HLA Antibodies

Platelet transfusion refractoriness (PTR) is a common complication in patients with hematological malignancies. It not only prolongs the duration of platelet transfusion dependence and significantly increases the risk of bleeding, but is also strongly associated with graft failure and reduced survival after transplantation. HLA class I antibody-mediated alloimmunization is recognized as the most important immunological cause of PTR. HLA antibodies are directly secreted by plasma cells, which are derived from B cells. Therefore, targeting B cells to reduce antibody production is a crucial step in eliminating HLA antibodies. Bruton's tyrosine kinase (BTK) is expressed throughout B cell development from the pre-B cell stage to maturity and supports B cell development, maturation, survival, proliferation, and antibody production by acting as a downstream kinase in the B cell receptor signaling pathway. Bortezomib, a proteasome inhibitor, can selectively induce apoptosis in long-lived plasma cells. The investigators' preliminary exploratory use of a BTK inhibitor in the treatment of PTR with HLA antibodies significantly reduced the mean fluorescence intensity (MFI) of HLA antibodies, improved platelet transfusion outcomes, and demonstrated a favorable safety profile. Based on these findings, the investigators are conducting a prospective, multicenter, randomized controlled two-arm study to investigate the efficacy and safety of acalabrutinib and bortezomib in eliminating HLA antibodies in hematological malignancies patients with PTR.

HLA Antibodies in Systemic Lupus Erythematosus

Patients suffering from autoimmune diseases show false-positive results when anti-HLA antibodies are identified. This false positivity makes it difficult to obtain an organ transplant based on immunological compatibility (absence of anti-HLA antibodies directed against graft antigens). The objectives of this project are to study the prevalence of these false positivities in a population of lupus patients, and to evaluate biological tests that can negate these false positivities.

TRAnscriptional Profile of Peripheral Blood Cells in Patient With Chronic Kidney and Lung Rejection: Correlation With Response to Extracorporeal Photo-aphereSiS

With this project, the research team aims to identify the molecular pathways associated with the response to extracorporeal photonchemioapheresis (ECP) in kidney or lung transplant patients suffering from chronic rejection, by analyzing gene expression in samples of peripheral blood mononuclear cells.