Treatment of donor-specific antibody-mediated rejection after heart transplantation by IgM-enriched human immunoglobulin

Abstract

Antibody-mediated graft rejection caused by donor-specific antibodies (DSA-MR) remains a serious problem after heart transplantation (HTx). IgM-enriched human intravenous immunoglobulin (IGM-IVIG) consists of 76% IgG, 12% IgM, and 12% IgA and provides a new multifactorial approach for DSA-MR. Between 2017 and 2020, four (P1-4) of 102 patients developed DSA-MR after HTx in our department and were repetitively treated with IGM-IVIG in combination with anti-thymocyte globulin. While in P1 and P4, DSA-MR occurred within the early post-operative interval, P2 and P3 developed DSA-MR approximately 1 year after transplantation. An impairment of ventricular function was observed in three of four patients. Furthermore, P1 and P4 suffered from malign ventricular arrhythmias. After the application of IGM-IVIG, the ventricular function recovered, and all patients could be discharged from the hospital. As part of a multifactorial therapeutic approach, treatment with IGM-IVIG seems to be a safe and effective strategy to address DSA-MR.

Keywords: Antibody mediated rejection; Donor specific antibody; Heart transplantation; IgM; Immunoglobulin.

Figure 1

Myocardial biopsy of a patient suffering from new‐onset malign arrhythmia displaying interstitial oedema, myocyte necrosis, karyohexis and inflammatory cell infitrates (A + B); CD3⁺‐lymphocytes, neutrophils, and mast cells (C); intravascular CD68⁺‐macrophages (D); and endothelial C4d‐depositions (E) as signs of severe AMR (pAMR3). (A) Haematoxylin, and eosin staining, 20‐times magnification; (B) haematoxylin and eosin staining, 40‐times magnification; (C) CD3‐antibody staining, 20‐times magnification; (D) CD68‐antibody staining, 40‐times magnification; (E) C4d‐antibody staining, 40‐times magnification. Figure adapted from Sipahi et al.