Use of a mouse–human chimeric anti-α-galactosidase A monoclonal antibody as a reference for measuring serum antidrug antibody titers in patients with Fabry disease

The detection of antidrug antibodies (ADAs) is important for monitoring patients with Fabry disease who are undergoing enzyme replacement therapy (ERT) with recombinant α-galactosidase A (GLA) drugs, as ADAs can cause allergic reactions and reduce therapeutic efficacy. Various immunological methods, particularly enzyme-linked immunosorbent assay (ELISA), are widely used to measure serum ADA titers in patients with Fabry disease. However, estimating and comparing results of ELISA is challenging because of the absence of a reference antibody. In this study, we developed a genetically engineered chimeric immunoglobulin G monoclonal antibody with mouse-derived variable regions that can react with recombinant GLA drugs and human constant regions that are necessary for recognition by the enzyme-conjugated antihuman signal antibody. Using this chimeric antibody as a reference, a new ELISA-based test was designed to measure anti-GLA antibody concentrations in serum samples. After validating the method, serum anti-GLA antibody titers were measured in 31 patients with Fabry disease, and three representative patients were monitored for 36 months after ERT initiation, achieving successful results, particularly in patients with high ADA titers.