Study of the effect of anti-rhGAA antibodies at low and intermediate titers in late onset Pompe patients treated with ERT

Mol Genet Metab. 2019 Sep-Oct;128(1-2):129-136. doi: 10.1016/j.ymgme.2019.07.013. Epub 2019 Jul 23.


Late onset Pompe disease (LOPD) is a genetic disorder characterized by slowly progressive skeletal and respiratory muscle weakness. Symptomatic patients are treated with enzyme replacement therapy (ERT) with alglucosidase alpha (rhGAA). Although most of ERT treated patients develop antibodies against rhGAA, their influence on clinical progression is not completely known. We studied the impact of anti-rhGAA antibodies on clinical progression of 25 ERT treated patients. We evaluated patients at visit 0 and, after 1 year, at visit 1. We performed several muscle function tests, conventional spirometry and quantitative muscle MRI (qMRI) using 3-point Dixon analysis of thigh muscles at both visits. We also obtained serum samples at both visits and anti-rhGAA antibodies were quantified using ELISA. Antibody titers higher than 1:200 were identified in 18 patients (72%) of our cohort. Seven patients (28%) did not develop antibodies (0 to <1:200), 17 patients (68%) developed low to intermediate titers (1:200 to <1:31,200) and 1 patient (4%) developed high titers (>1:31,200). We analyzed the effect of low and intermediate antibody titers in clinical and radiological progression. There were no differences between the results of muscle function tests, spirometry or fat fraction analyzed using qMRI between patients with and without antibodies groups at baseline. Moreover, antibody titers did not influence muscle function test, spirometry results or qMRI results at year 1 visit. Most of the LOPD patients developed antibodies against ERT that persisted over time at low or intermediate levels. However, antibodies at these low and intermediate titers might not influence clinical response to the drug.

Keywords: Antibodies; ERT; Enzyme replacement therapy; LOPD; Late onset Pompe disease.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibodies / blood*
  • Enzyme Replacement Therapy*
  • Female
  • Glycogen Storage Disease Type II / drug therapy*
  • Humans
  • Late Onset Disorders / drug therapy*
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Muscle, Skeletal / drug effects
  • Prospective Studies
  • alpha-Glucosidases / immunology*


  • Antibodies
  • GAA protein, human
  • alpha-Glucosidases