Bacterial enzymes that specifically break down IgG antibodies have gained increased interest recently, as they have the potential to have a significant impact on the treatment of allo-and autoimmune disorders. The Immunoglobulin G-degrading enzyme of Streptococcus pyogenes (IdeS) is normally secreted by S. pyogenes during infection. IdeS is now known as imlifidase, and clinical trials have been published on HLA-sensitized candidates for renal transplantation and anti-glomerular basement membrane disease. 1,2 Imlifidase has been studied in a range of hematologic disorders as well. A short overview is given here.
WORKING MECHANISM OF IMLIFIDASEAn IgG molecule consists of two heavy and two light chains held together by disulfide bonds. Imlifidase has a unique specificity for IgG and cleaves IgG in the heavy chains, which generates one F(ab՛)2 and two monomeric Fc fragments 3 (Figure 1). This leads to a rapid degradation of all circulating IgG within 6 h, with antibody levels returning to baseline around Day 14 postinfusion. 4 Imlifidase itself will be cleared from the circulation within 24 h. The theoretical concept for imlifidase is that antibody-driven disorders could temporarily be mitigated.