title: Persistence of high sustained antibodies to enzyme replacement therapy despite extensive immunomodulatory therapy in an infant with Pompe disease: need for agents to target antibody-secreting plasma cells.
abstract: With the advent of enzyme replacement therapy (ERT) with alglucosidase alfa (rhGAA, Myozyme®) for Pompe disease, the clinical course of the disease has changed. We have previously described the poor outcome in cross reactive immunologic material (CRIM)-negative and high-titer CRIM-positive (HTCP) patients secondary to high sustained antibody titers (HSAT) which effectively neutralize ERT efficacy. Various immunomodulation strategies are being explored to diminish the immune response to ERT. However, once HSAT are formed, tolerization therapy has uniformly failed to lower antibody titers. Here we describe a case in which immunomodulation over a prolonged period of 28 months with cyclophosphamide, intravenous immunoglobulin, plasmapheresis, increased doses of rhGAA and rituximab failed to lower antibody titers and resulted in continued clinical decline in an infantile Pompe disease patient treated with ERT. Thus, it appears that the failure to target the antibody-secreting plasma cells responsible for HSAT led to a failure of tolerance induction. This is the first report using this combination of agents over a very extensive period of time with no success.
authors.affiliation: Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Suhrad G
authors.initials: SG
authors.lastname: Banugaria
authors.forename: Trusha T
authors.initials: TT
authors.lastname: Patel
authors.forename: Joanne
authors.initials: J
authors.lastname: Mackey
authors.forename: Stuti
authors.initials: S
authors.lastname: Das
authors.forename: Andrea
authors.initials: A
authors.lastname: Amalfitano
authors.forename: Amy S
authors.initials: AS
authors.lastname: Rosenberg
authors.forename: Joel
authors.initials: J
authors.lastname: Charrow
authors.forename: Y-T
authors.initials: YT
authors.lastname: Chen
authors.forename: Priya S
authors.initials: PS
authors.lastname: Kishnani
mesh_terms: D000921:Antibody-Producing Cells / Q000276:immunology*; D056947:Enzyme Replacement Therapy; D006009:Glycogen Storage Disease Type II / Q000201:enzymology / Q000276:immunology* / Q000628:therapy*; D006801:Humans; D056747:Immunomodulation; D007223:Infant; D008297:Male; D010950:Plasma Cells / Q000276:immunology*; D016896:Treatment Outcome; D000520:alpha-Glucosidases / Q000276:immunology*
chemical_list: C509951:GAA protein, human; D000520:alpha-Glucosidases