Immune response to enzyme replacement therapy: 4-sulfatase epitope reactivity of plasma antibodies from MPS VI cats

The mucopolysaccharidoses (MPS) are a group of multiple pathology disorders which are part of a larger group of genetic diseases known as lysosomal st orage disorders. Enzyme replacement therapy (ERT) has been developed as a t herapy for MPS patients. However, immune responses to ERT have been reporte d in MPS animal models and in human Gaucher patients. Antibodies can have a dverse effects during ERT, which include hypersensitivity/anaphylactic reac tions, enzyme inactivation, and enzyme degradation. This study aimed to cha racterize the immune response to ERT in a feline model of MPS VI, by defini ng the epitope reactivity of cat plasma antibody against human recombinant N-acetylgalactosamine 4-sulfatase (4-sulfatase) replacement protein. For MP S VI cat plasma, antibody reactivity was observed prior to ERT, with distin ct regions of 4-sulfatase linear sequence displaying low affinity antibody reactivity, There was an increase in antibody titer to 4-sulfatase for MPS VI cats post-ERT, with the majority of the immune response detected to line ar sequence epitopes. One cat displayed a high titer and high affinity epit ope reactivity following prolonged exposure (greater than or equal to 9 mon ths) to the replacement protein. MPS VI cats on shorter term ERT (3 months) showed high titers to 4-sulfatase and similar patterns of epitope reactivi ty, but lower affinity antibody reactivity, when compared to the latter cat . This study reports the linear amino acid sequence reactivity and nature o f the immune response produced to 4-sulfatase before and after ERT, The mon itoring of antibody production during replacement therapy is an important c onsideration for patient management, as high titer antibodies can affect th e efficacy of therapy. (C) 1999 Academic Press.