Transplant immunology · 2025
Rituximab-based antibody mediated rejection therapy modestly reduces Xenoreactive antibodies: Implications for pig-to-human xenotransplantation.
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Yeh Szu-Tsen, Marshall Nicole A, Lehman Brent P, Rubinstein C Dustin, Shanmuganayagam Dhanansayan, Meudt Jennifer J, Redfield Robert R, Hidalgo Luis G, Dominko Tanja, Aufhauser David D
Аннотация
BACKGROUND: Anti-pig antibodies, including those targeting porcine glycans and swine leukocyte antigens, present a significant challenge to pig-to-human xenotransplantation. Current strategies for managing these antibodies are limited. We examine the impact of standard antibody-mediated rejection (ABMR) therapy in human kidney transplant recipients on the levels of xenoreactive anti-pig antibodies.
METHODS: We analyzed serum samples from 25 kidney transplant recipients with biopsy-proven ABMR treated with corticosteroids, intravenous immunoglobulin (IVIG), and rituximab. Anti-pig IgG and IgM titers were measured by flow cytometry. We assessed changes in anti-pig antibody mean fluorescence intensity (MFI) at baseline, 3, and 6 months post-treatment. We also correlated changes in anti-pig antibody levels with donor-specific anti-HLA antibodies (DSA).
RESULTS: Rituximab-based ABMR therapy resulted in a modest reduction (∼21-29 % reduction) of anti-pig IgG levels at 3 months (p < 0.01) and at 6 months (p < 0.05). Anti-pig IgM levels demonstrated a similar but less consistent trend. Higher baseline DSA levels, particularly anti-HLA Class II, were associated with increased anti-pig IgG binding. However, the reductions in anti-pig antibodies did not correlate with changes in DSA levels post-treatment.
CONCLUSIONS: ABMR therapy that includes rituximab, IVIG, and corticosteroids leads to a modest decrease in anti-pig IgG levels, even when DSA levels are effectively neutralized. These findings highlight the limitations of current desensitization therapies and underscore the need for improved humoral-targeted therapies to support safe and durable clinical xenotransplantation.
METHODS: We analyzed serum samples from 25 kidney transplant recipients with biopsy-proven ABMR treated with corticosteroids, intravenous immunoglobulin (IVIG), and rituximab. Anti-pig IgG and IgM titers were measured by flow cytometry. We assessed changes in anti-pig antibody mean fluorescence intensity (MFI) at baseline, 3, and 6 months post-treatment. We also correlated changes in anti-pig antibody levels with donor-specific anti-HLA antibodies (DSA).
RESULTS: Rituximab-based ABMR therapy resulted in a modest reduction (∼21-29 % reduction) of anti-pig IgG levels at 3 months (p < 0.01) and at 6 months (p < 0.05). Anti-pig IgM levels demonstrated a similar but less consistent trend. Higher baseline DSA levels, particularly anti-HLA Class II, were associated with increased anti-pig IgG binding. However, the reductions in anti-pig antibodies did not correlate with changes in DSA levels post-treatment.
CONCLUSIONS: ABMR therapy that includes rituximab, IVIG, and corticosteroids leads to a modest decrease in anti-pig IgG levels, even when DSA levels are effectively neutralized. These findings highlight the limitations of current desensitization therapies and underscore the need for improved humoral-targeted therapies to support safe and durable clinical xenotransplantation.