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ABO-Incompatible Liver Transplantation and Humoral Immune Tolerance

Jun 26, 2017 11:20:50 AM / by Stacy Matthews Branch, DVM, PhD

Liver operation puzzle concept: hands of surgeon with surgical instruments (tools) performs liver surgery as a result of hepatic disorder (cirrhosis, hepatic cancer, hepatitis, hepatectomy)ABO-incompatible liver transplantation has an elevated risk of humoral (antibody mediated) rejection. The age at transplantation and the level of anti-donor blood group antibodies are risk factors for transplant rejection. There are cases in which there is no humoral response to ABO blood group antigens with incompatible liver transplantation. To determine the possible mechanism of this phenomenon, researchers examined the capability of anti-donor ABO antibody production by peripheral blood mononuclear cells from patients with incompatible liver transplants. 

Peripheral blood mononuclear cells were obtained from patients with blood-types B or O and who had incompatible liver transplants. There were three groups of patients with incompatible transplants, 1) those who received preoperative rituximab induction (immunosuppressive therapy to prevent acute organ rejection during the early post-transplantation period), 2) those without preoperative rituximab induction, and 3) pediatric patients (under 15 years of age) without preoperative rituximab induction. Also included in the study were ABO-identical/compatible patients and healthy volunteers. 

At the beginning of the study, the peripheral blood mononuclear cells from the patients were engrafted via intraperitoneal injections into laboratory mice. These now chimeric mice with humanized peripheral blood mononuclear cells were exposed to type A red blood cells on days 5, 7, and 9. On study day 21, sera were collected from the mice, and levels of Anti-A antibody were measured by flow cytometry. No Anti-A antibody was detected in the sera of patients. However, Anti-A antibody was detected in mice with adult patient peripheral blood mononuclear cells (induced with rituximab or not). Anti-A production was also seen with ABO-identical/compatible and healthy volunteer cells. 

Interestingly, Anti-A antibody production was suppressed in the peripheral blood mononuclear cells from pediatric patients. Therefore, production of anti-donor antibody occurs in the peripheral mononuclear cells of adults, and pediatric patients with incompatible transplants are unresponsiveness to ABO antigens. These findings suggest that exposure to anti-donor ABO antigens during stages of humoral immune response development is a critical factor in humoral immune tolerance with organ transplantation. 

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Ueda, D., Yoshizawa, A., Hirata, Y., Kaneshiro, M., Maekawa, T., & Uemoto, S. (2017). The Capability of Anti-ABO-Blood-Type Antibodies Production in Peripheral Blood Mononuclear Cells after ABO-Incompatible Liver Transplantation. Transplantation, 101, S39. doi:10.1097/

Topics: Mononuclear Cells, PBMCs

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