New Therapies for Highly Sensitized Patients on the Waiting List.
Newer desensitization agents such as imlifidase can rapidly clear circulating IgG to open a transplant window for very highly sensitized patients, but pathogenic antibody rebound remains a key barrier that future combination strategies aim to control.
Background
Exposure to HLA alloantigens through pregnancy, blood products, and prior transplantation generates strong alloimmune responses that create an immunologic barrier to transplantation, detected by HLA antibody screening. Patients with calculated panel reactive antibody of 99 to 100 percent are especially difficult to transplant because conventional approaches often cannot remove high-titer antibodies or limit rebound from long-lived plasma cells and memory B cells.
Key recommendations
Currently accepted desensitization combines plasmapheresis or low- or high-dose intravenous immunoglobulin with anti-CD20 therapy, but these are frequently unsuccessful in the most sensitized patients. Imlifidase, an IgG endopeptidase, rapidly inactivates IgG by cleaving it into F(ab')2 and Fc fragments, creating an antibody-free zone that eliminates complement- and cell-mediated graft injury and represents an important advance, though its efficacy is limited by antibody rebound.
Clinical implications
Controlling antibody rebound will likely require combining rapid antibody depletion with agents that suppress B-memory and plasma-cell responses, such as anti-IL-6 receptor (tocilizumab) or anti-IL-6 (clazakizumab), plasma-cell-directed agents (anti-CD38 and anti-BCMA x CD3), complement inhibitors, and FcRn inhibitors of IgG recycling. Used alone or in combination, these advanced therapeutics are expected to improve desensitization efficacy and expand access to kidney transplantation for highly HLA-sensitized patients.
Category
Transplant
Source
Kidney360
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