Acquired Downregulation of Donor-Specific Antibody Production After ABO-Incompatible Kidney Transplantation

Abstract

The mechanism of long-term B cell immunity against donor blood group antigens in recipients who undergo ABO-incompatible (ABOi) living-donor kidney transplantation (LKTx) is unknown. To address this question, we evaluated serial anti-A and anti-B antibody titers in 50 adult recipients. Donor-specific antibody titers remained low (≤1:4) in 42 recipients (84%). However, antibodies against nondonor blood group antigens were continuously produced in recipients with blood type O. We stimulated recipients' peripheral blood mononuclear cells in vitro to investigate whether B cells produced antibodies against donor blood group antigens in the absence of graft adsorption in vivo. Antibodies in cell culture supernatant were measured using specific enzyme-linked immunosorbent assays (ELISAs). Thirty-five healthy volunteers and 57 recipients who underwent ABOcompatible LKTx served as controls. Antibody production in vitro against donor blood group antigens by cells from ABOi LKTx patients was lower than in the control groups. Immunoglobulin deposits were undetectable in biopsies of grafts of eight recipients with low antibody titers (≤1:4) after ABOi LKTx. One patient with blood type A1 who received a second ABOi LKTx from a type B donor did not produce Bspecific antibodies. These findings suggest diminished donor-specific antibody production function in the setting of adult ABOi LKTx.

Analysis of the prevalence of systemic de novo thrombotic microangiopathy after ABO‐incompatible kidney transplantation and the associated risk factors

“…Titration of anti‐A and anti‐B antibodies was carried out using the test tube method, as described in …”

Effect of simultaneous presence of anti-blood group A/B and -HLA antibodies on clinical outcomes in kidney transplantation across positive crossmatch: a nationwide cohort study

“…Takahashi believed that AMR due to anti-blood group A, B Ab is mainly caused by not natural but by de novo Ab, resulting occurrence especially two to seven days after transplant, which is called the “critical period” 21 . After stabilization of graft function, down-regulation of Ab production against the donor ABO antigen was acquired 22 . A phenomenon that the patients remain not rejected in the presence of a circulating antibody can be a possible theory for the relatively lower antigenicity of ABO-i KT than that of HLA-i KT 20,23,24 .…”

Molecular Mechanisms of Antibody-Mediated Rejection and Accommodation in Organ Transplantation

“…On the contrary, small amount of anti-HLA-class I antibody enhanced the AKT survival signal [22], which is associated with HO-1 and ferritin H protein [23, 24]. Another aspect of accommodation was partly explained by the decreased production of donor-specific anti-A/B antibodies in graft recipients of ABO-incompatible kidney transplants [25]. Although infrequently observed in organ transplantation, the effort to investigate the mechanisms to acquire the accommodation might shed light on avenues for prevention of transplant rejection and new opportunities to elicit repair mechanisms from DSA-mediated injury.…”