Significance of low-level DSA detected by solid-phase assay in association with acute and chronic antibody-mediated rejection

We sought to clarify the controversial issue of whether detecting low-level anti-donor-specific HLA antibody (HLA-DSA) by single-antigen flow-bead assay (SAFB) may have a potential role in reducing acute and chronic antibody-mediated rejection (AMR). We retrospectively studied the preoperative serum of ABO-compatible living kidney transplantation recipients transplanted between 2001 and 2004 by SAFB using a Luminex platform. HLA-DSA was detected only by SAFB in 24 patients, although all of them showed negative T-cell and B-cell complement-dependent cytotoxicity (CDC) crossmatches. The HLA-DSA patients went on to have surprisingly high levels of acute and chronic AMR despite being only weakly sensitized (acute AMR, 33.3%; chronic AMR, 41.7%). After 2005, we implemented SAFB routinely and any patient having a positive HLA-DSA was considered to be a desensitization candidate. The 52 patients found to have HLA-DSA underwent kidney transplantation after prior treatment with a single dose of rituximab (RIT) and three or four sessions of double-filtration plasmapheresis (DFPP) in addition to regimens commonly used between 2001 and 2004. After 2005, there was a significant reduction in the occurrence of acute and chronic AMR (acute AMR, 4.7%, P < 0.001; chronic AMR, 4.7%, P < 0.001). The 5-year graft survival rate also improved after implementing SAFB (83.3–98.1%, P = 0.032). The RIT/DFPP-induction protocol may improve graft survival even in patients with low-level DSA (read more).

Identification and therapeutic management of highly sensitized patients undergoing renal transplantation.

Sensitization is generally referred to as the development of alloantibodies, specifically anti-human leukocyte antigen (HLA) immunoglobulin G (IgG) antibodies, most commonly caused by pregnancy, blood transfusion or a previous transplant. Despite being a well known phenomenon, there has not been a general consensus on its definition, monitoring or management. Today, 25% of the patients waitlisted for kidney transplant in the US have a panel reactive antibody (PRA) of >10% while, in the Eurotransplant zone, 14% have a PRA of >5%. Sensitized patients have more difficulty in finding a well HLA-matched donor, and have a higher risk of experiencing longer waiting times, more rejection episodes and eventually inferior long-term graft or patient survival. We review the currently available strategies in identifying and managing highly sensitized patients undergoing renal transplantation. We discuss the progress and limitations in laboratory techniques to elaborate on challenges in defining sensitized patients. The main management options (i.e. the Acceptable Mismatch Program, donor exchange programmes and the desensitization approach) and their mechanisms, related policies, advantages and outcomes, as well as medications and methods being investigated, are updated. In addition, particular emphasis is given to sensitization prevention, a practice that is neglected with our increasing ability to suppress the immune system (read more)