From the Guidelines
Management of chronic rejection with anti-HLA B antibodies at an MFI of 3500 requires a multifaceted approach, and I recommend intensifying immunosuppression with optimization of calcineurin inhibitor levels, ensuring adequate mycophenolate mofetil dosing, and considering a steroid pulse followed by a prednisone taper. For antibody reduction, plasmapheresis combined with IVIG should be initiated, and rituximab may be added to target B cells. The most recent and highest quality study 1 suggests that tacrolimus trough levels should be kept at 6-10 ng/ml during the first month followed by 4-8 ng/ml thereafter, and it is recommended to combine tacrolimus with other immunosuppressive drugs to allow for a lower range of tacrolimus trough levels and to help preserve renal function. Some key points to consider in the management of chronic rejection include:
- Intensifying immunosuppression with optimization of calcineurin inhibitor levels (tacrolimus target trough of 6-10 ng/mL or cyclosporine 100-150 ng/mL) 1
- Ensuring adequate mycophenolate mofetil dosing (1-1.5g twice daily)
- Considering a steroid pulse (methylprednisolone 500mg IV for 3 days) followed by a prednisone taper to a maintenance dose of 5-10mg daily
- For antibody reduction, plasmapheresis (3-5 sessions) combined with IVIG (0.5-1g/kg after each session) should be initiated 1
- Rituximab (375mg/m² weekly for 2-4 doses) may be added to target B cells 1
- For maintenance therapy, consider adding an mTOR inhibitor like everolimus (target trough 3-8 ng/mL) or sirolimus (target trough 5-10 ng/mL) 1
- Close monitoring is essential with biweekly creatinine measurements, monthly donor-specific antibody levels, and protocol biopsies at 3 and 6 months. This approach addresses both the cellular and humoral components of rejection, targeting the anti-HLA antibodies that are mediating the chronic rejection process while preventing further antibody formation through enhanced immunosuppression.
From the Research
Management of Chronic Rejection with Anti-HLA B Antibodies
- The management of chronic rejection with the presence of anti-Human Leukocyte Antigen (HLA) B antibodies at a Mean Fluorescence Intensity (MFI) of 3500 is a complex process that involves multiple treatment approaches 2, 3, 4, 5, 6.
- Treatment options for antibody-mediated rejection (AMR) include the use of high-dose intravenous immunoglobulin (IVIG), rituximab, and plasmapheresis 3.
- The combination of rituximab and IVIG has been shown to be effective in early-stage chronic active antibody-mediated rejection (CAMR), but the effect is limited in advanced stages 2.
- Other treatment strategies include the use of lymphocyte-depleting agents such as antithymocyte globulin (ATG) and the blockade of antibody-mediated tissue injury using anti-inflammatory, anti-coagulation, and complement blockade agents 4.
- The treatment of chronic AMR (CAMR) is not well characterized, but it is thought to be amenable to suppression by heightening of maintenance immunosuppression and anti-idiotypic blockade of the circulating alloantibody without the need for plasma exchange 6.
- New pharmacotherapeutic options, such as alemtuzumab, belatacept, and IL-6 receptor antagonists, are being explored for the prevention and treatment of AMR and CAMR 5.
Treatment Approaches
- IVIG therapy: works by blocking anti-HLA antibody activity and through complement inhibition 3.
- Rituximab therapy: depletes B cells and interferes with antigen-presenting cell (APC) activity of B cells, subsequently decreasing T-cell activation 3.
- Plasmapheresis: removes deleterious anti-HLA antibodies and may also allow complexing of anti-HLA with anti-idiotypes in the anti-CMV IgG 3.
- ATG monotherapy: has a significant depleting effect on B cells, but its effects on donor-specific antibodies (DSAs) are not ideal 4.
- Combination therapy: using a combination of rituximab, IVIG, and plasmapheresis may be effective in treating AMR, but its effectiveness in CAMR is not well established 4.