*Purpose: Immunoglobulin-degrading enzyme from Streptococcus pyogenes (IdeS, Imlifidase) has been used to reduce antibody levels to promote transplant of highly sensitized patients. In vitro experiments suggest that IdeS specifically cleaves IgG, but not IgM and IgA molecules, into the F(ab’)₂ and Fc fragments. In this study, we examined levels of anti-HLA IgM in patients pre- and post-treatment with Imlifidase.

*Methods: 10 HLA-sensitized patients treated with IdeS were evaluated for the presence of anti-HLA IgM. Anti-HLA IgM antibodies were detected by single antigen beads based assay using fluorescence labeled secondary antibody F(ab’)₂ fragment specific to IgM. IdeS does not affect the activity of the F(ab’)₂ fragment. Mean fluorescence intensity (MFI) of antibodies was compared in the pre- and 24 hrs post-IdeS infusion samples. 50% decrease of MFI was considered significantly different.

*Results: Anti-HLA IgM was detected in 9 of 10 patients pre-Imlifidase infusion. Of the 9 IgM positive patients, 3 patients had anti-HLA IgM with MFI >10,000; 3 patients had anti-HLA IgM with MFI >5,000; and other 3 patients had anti-HLA IgM with MFI >2,500. Imlifidase treatment significantly reduced MFI of anti-HLA IgM in 4 patients (Figure 1). Of these 4 patients, 3 patients had IgM MFI>10,000, and 1 patient had IgM with MFI >5,000 pre-Imlifidase infusion. In contrast, patients who had anti-HLA IgM with MFI<5,000 pre-IdeS infusion, did not show a decrease in MFI.

*Conclusions: Surprisingly, we found that Imlifidase treatment decreased levels of anti-HLA IgM in vivo. Of interest was higher efficacy of Imlifidase treatment observed in patients with higher levels of anti-HLA IgM. Our results indicate that the potential use of Imlifidase to reduce pathogenic IgM antibodies should be investigated.

« Back to 2019 American Transplant Congress