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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.
Mol Genet Metab 2012; 105(4):677-80MG

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+Show Affiliations

Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, NC 27710, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Case Reports
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22365055

Citation

Banugaria, Suhrad G., et al. "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." Molecular Genetics and Metabolism, vol. 105, no. 4, 2012, pp. 677-80.
Banugaria SG, Patel TT, Mackey J, et al. 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. Mol Genet Metab. 2012;105(4):677-80.
Banugaria, S. G., Patel, T. T., Mackey, J., Das, S., Amalfitano, A., Rosenberg, A. S., ... Kishnani, P. S. (2012). 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. Molecular Genetics and Metabolism, 105(4), pp. 677-80. doi:10.1016/j.ymgme.2012.01.019.
Banugaria SG, et al. 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. Mol Genet Metab. 2012;105(4):677-80. PubMed PMID: 22365055.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Banugaria,Suhrad G, AU - Patel,Trusha T, AU - Mackey,Joanne, AU - Das,Stuti, AU - Amalfitano,Andrea, AU - Rosenberg,Amy S, AU - Charrow,Joel, AU - Chen,Y-T, AU - Kishnani,Priya S, Y1 - 2012/01/28/ PY - 2011/12/13/received PY - 2012/01/24/revised PY - 2012/01/24/accepted PY - 2012/2/28/entrez PY - 2012/3/1/pubmed PY - 2012/7/17/medline SP - 677 EP - 80 JF - Molecular genetics and metabolism JO - Mol. Genet. Metab. VL - 105 IS - 4 N2 - 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. SN - 1096-7206 UR - https://www.unboundmedicine.com/medline/citation/22365055/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_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1096-7192(12)00023-6 DB - PRIME DP - Unbound Medicine ER -