Treatment of Donor-Specific Antibody Mediated Rejection after Heart Transplantation by IGM-Enriched Human Intravenous Immunoglobulin

Purpose Representing a rare complication, antibody-mediated graft rejection (AMR), particularly caused by donor-specific antibodies (DSA), remains a serious problem after heart transplantation (HTx). Plasmapheresis, application of rituximab as well as intravenous immunoglobulins (IVIG) are widely established, however often insufficient treatments for AMR. IgM-enriched human intravenous immunoglobulin (IGM-IVIG) consists of IgM, IgA and IgG and provides a new multifactorial approach to the immunologic cascade of DSA-mediated AMR, however its efficiency is by now still not clear. Methods Between 2017 and 2020 four patients (P 1-4) developed DSA-mediated rejection (DSA-MR) after HTx in our department and were repetitively treated with 0.5-1.0 g/kg body weight IGM-IVIG (Pentaglobin®, Biotest AG, Dreieich, Germany) in combination with 3.0 mg/kg body weight anti-thymocyte globulin (ATG). Results Patients were transplanted at the age of 47 (P1), 57 (P2), 30 (P3) and 68 years (P4). Except P2, all patients were male. While in P1 and P4, DSA-MR occurred within the early postoperative interval after HTx, P2 and P3 developed DSA-MR one year after transplantation. In all patients donor-specific HLA-antibodies were found, however pathological examinations of right ventricular biopsies could only confirm AMR in P1-3 (pAMR1° to pAMR3°) but not in P4 (pAMR0). A severe impairment of biventricular function was observed in all patients with need for temporary veno-arterial extracorporeal membrane oxygenation (va-ECMO) in P4. Furthermore, P1 and P4 suffered from malign ventricular arrhythmias. After repetitive application of IGM-IVIG all patients could be stabilized, ventricular function recovered, and P1-3 could be discharged from hospital and are still alive today, whereas P4 has been transplanted quite recently and is still recovering in hospital. Conclusion DSA-MR provokes serious complications affecting the outcome after HTx. By application of IGM-IVIG, we were able to successfully treat all of our four patients suffering from severe graft failure caused by DSA-MR and no patient developed treatment-related adverse effects. As part of a multifactorial therapeutic approach, pharmacological treatment with IGM-IVIG seems to be a safe and effective strategy in order to address DSA-MR and offers promising results for the future.