Donor-Specific Anti-HLA Antibodies in Organ Transplantation: Transition from Serum DSA to Intra-Graft DSA

Abstract

In the field of organ transplantation, donor-specific anti-HLA antibodies (DSA) have gained more popularity, as antibody-mediated rejection (AMR) has been recognized as an important factor to determine allograft survival. Thus, it is reasonable to believe that appropriate control of DSA is directly linked to well-managed immunosuppression, resulting in free from AMR. First, in order to prevent and manage AMR, it is of vital importance to be familiar with updated knowledge regarding crossmatch test and DSA detection methods, including intra-graft DSA. Second, it is also crucial to understand the standard criteria to diagnose AMR. Although pathological diagnosis and serum DSA (s-DSA) detection play the central role, the recent trend seems to be detection of intra-graft DSA (g-DSA). Third, regarding organ transplantation between sensitized pairs, the acceptable outcomes are obtained owing to recent preoperative desensitization protocols: depletion/modification of B cells, apheresis for antibodies, and inhibition of reaction between DSA and HLA. Finally, we would like to discuss the treatment of AMR. Further advances in diagnosis methods and emergences of effective treatments would be expected for acceptable control of AMR. In this chapter, we will review from the basics to recent topics in order to understand DSA and AMR.

The Role of Major Histocompatibility Complex in Organ Transplantation- Donor Specific Anti-Major Histocompatibility Complex Antibodies Analysis Goes to the Next Stage -

“…In this section, we will review methods which are frequently applied in the field of organ transplantation. These techniques are also well reviewed in elsewhere [93]. To detect humoral factor: DSA, originally, LCT or the complement dependent cytotoxicity (CDC) crossmatch test was reported in the 1960s (8).…”

Antibody-Mediated Rejection and Recurrent Primary Disease: Two Main Obstacles in Abdominal Kidney, Liver, and Pancreas Transplants

“…A variety of therapeutic approaches have been implemented, owing to the recent development of synthetic antibodies, in addition to orthodox therapeutic modalities. Several institutions applied steroid pulse, plasmapheresis, and intravenous immunoglobulin therapy (IVIG), combined with anti-CD 20 Abs administration for dnDSA mediated ABMR [18]. Other than these conventional therapies, several monoclonal Abs including eculizumab (anti-C5), tocilizumab, and clazakizumab (anti-interleukin 6) have recently been introduced in this field, although a proteasome inhibitor (bortezomib) failed to show therapeutic effects [19].…”