Date: Saturday, June 2, 2018
Session Time: 5:30pm-7:30pm
Presentation Time: 5:30pm-7:30pm
Location: Hall 4EF
Background: It has been reported that preformed donor-specific anti-human leukocyte antigen antibodies (DSAs) were associated with poor graft outcomes in kidney transplant recipients. To eliminate preformed DSAs, we desensitized DSA-positive patients by injecting rituximab and then performed plasmapheresis in those patients using a protocol for ABO-incompatible (ABO-I) transplant recipients. B-cell depletion with rituximab may influence T-cell responses to alloantigens since B-cells are effective antigen-presenting cells that are capable of activating donor-specific T-cells. It is also likely that the cytokine release syndrome, which is caused by rituximab, may enhance T-cell activation. In this study, we investigated the impact of pre-transplant desensitization with rituximab on the subsequent response of T-cells to alloantigens in DSA-positive kidney transplant recipients.
Methods: Fourteen DSA-positive patients of kidney allografts were employed in this study, while 26 DSA-negative ABO-I recipients of kidney allografts formed the control group that received a similar desensitization preconditioning with rituximab and plasmapheresis. To monitor the recipients' immune status, a mixed lymphocyte reaction assay using a CFSE-labeling technique was performed before and after desensitization.
Results: Before desensitization, there were no significant differences in the average stimulation index (SI) values for the responses of the CD4+ and CD8+ T-cells to donor stimuli between the two groups. However, after desensitization, the average SI values for the CD4+ T-cells were significantly higher in the DSA-positive patients than those in the DSA-negative ABO-I patients. Patients with high SI values were treated with rabbit thymocyte globulin (rATG), and neither antibody-mediated rejection nor severe acute cellular rejection was encountered in these patients after transplantation.
Conclusions: These findings demonstrate that B-cell depletion with rituximab exacerbates anti-donor CD4+ T-cell responses in DSA-positive organ transplant recipients. It might be possible that treatment with rituximab undesirably depletes specific B-cell subsets that could regulate T-cell responses to alloantigens. Although this issue is currently under investigation, T-cell responses could possibly be inhibited by rATG before or after desensitization to prevent ACR events.
CITATION INFORMATION: Tanaka A., Ide K., Tanaka Y., Ohira M., Tahara H., Shimizu S., Ohdan H. B-Cell Depletion with Rituximab Exacerbates Anti-Donor CD4+ T-Cell Responses in Patients with Donor-Specific Anti-Human Leukocyte Antigen Antibodies Am J Transplant. 2017;17 (suppl 3).
To cite this abstract in AMA style:Tanaka A, Ide K, Tanaka Y, Ohira M, Tahara H, Shimizu S, Ohdan H. B-Cell Depletion with Rituximab Exacerbates Anti-Donor CD4+ T-Cell Responses in Patients with Donor-Specific Anti-Human Leukocyte Antigen Antibodies [abstract]. https://atcmeetingabstracts.com/abstract/b-cell-depletion-with-rituximab-exacerbates-anti-donor-cd4-t-cell-responses-in-patients-with-donor-specific-anti-human-leukocyte-antigen-antibodies/. Accessed September 18, 2019.
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