The Capability of Anti-ABO-Blood-Type Antibodies Production in Peripheral Blood Mononuclear Cells after ABO-Incompatible Liver Transplantation

Abstract

Introduction: The anti-donor ABO antibody (Ab) titer doesn’t elevate in long-term followed-up ABO incompatible liver transplant (i-LTx) patients and antibody mediated rejection does not occur in the late graft liver according to our experience. To clarify the mechanism of unresponsiveness to ABO antigens, we examined the capability of the peripheral blood mononuclear cells (PBMCs) of long-term followed-up i-LTx patients to produce anti-donor ABO antibodies. Methods: The study subjects were the patients with blood-type B and O who had undergone i-LTx with preoperative rituximab induction (n = 5), without preoperative rituximab induction (n = 5), pediatric patients (under 15 years old at transplantation) without preoperative rituximab induction (n = 5), ABO-identical/compatible patients (n = 5), and healthy volunteers (n = 5). On day 0, 1 × 107 cells of PBMCs, obtained from the subjects, are engrafted into NOG mice by peritoneal injections. Mice, which chimerized with human PBMCs, were sensitized with A red blood cells on day 5, 7, and 9. On day 21, the sera were collected. Anti A Abs (IgM and IgG) were examined by flow cytometric analysis. Result: Anti A Ab titers of all the patients with i-LTx patients are hardly detected in the sera from the subjects. In chimeric mice, the production of anti A antibodies of pediatric recipients’ PBMCs was also suppressed. But, the ability of PBMCs to produce anti-A Abs still remained in the adult patients’ PBMCs regardless of perioperative rituximab induction. The production of anti A Ab was observed in identical/compatible patients and healthy volunteers (figure 1). Conclusion: The immune unresponsiveness to ABO antigens has existed in PBMCs from the i-LT pediatric patients. On the other hand, in the adult recipients, the ability to produce anti-donor ABO antibodies was maintained in PBMCs. This suggests that the timing of exposure to ABO antigens during evolution of humoral immune response is crucial to establish humoral immune tolerance.Figure