期刊
MOLECULAR GENETICS AND METABOLISM REPORTS
卷 4, 期 -, 页码 30-34出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ymgmr.2015.05.004
关键词
Infantile Pompe disease; Immune tolerance induction; High sustained antibody titers; Bortezomib
资金
- ACTSI KL2-Mentored Clinical and Translational Research Program
- National Institutes of Health (NIH) [KL2TR000455]
- Genzyme Corporation
- Sanofi Company (Cambridge, MA)
- Lysosomal Disease Network
- NIH RDCRN [U54NS065768]
- NIH Office of Rare Diseases Research (ORDR) at the National Center for Advancing Translational Science (NCATAS)
- National Institute of Neurological Disorders and Stroke (NINDS)
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- University of Minnesota and Lysosomal Disease Network fellowship [NIH U54NS065768]
- NIH Rare Diseases Clinical Research Network (RDCRN)
Enzyme replacement therapy (ERT) has led to a significant improvement in the clinical course of patients with infantile Pompe disease (IPD), an autosomal recessive glycogen storage disorder characterized by the deficiency in lysosomal acid alpha-glucosidase. A subset of IPD patients mounts a substantial immune response to ERT developing high sustained anti-rhGAA IgG antibody titers (HSAT) leading to the ineffectiveness of this treatment. HSAT have been challenging to treat, although preemptive approaches have shown success in high-risk patients (those who are cross-reactive immunological material [CRIM]-negative). More recently, the addition of bortezomib, a proteasome inhibitor known to target plasma cells, to immunotherapy with rituximab, methotrexate, and intravenous immunoglobulin has shown success at significantly reducing the anti-rhGAA antibody titers in three patients with HSAT. In this report, we present the successful use of a bortezomib-based approach in a CRIM-positive IPD patient with HSAT and the use of a preemptive approach to prevent immunologic response in an affected younger sibling. We highlight the significant difference in clinical course between the two patients, particularly that a pre-emptive approach was simple and effective in preventing the development of high antibody titers in the younger sibling, thus supporting the role of immune tolerance induction (ITI) in the ERT-naive high-risk setting. (C) 2015 The Authors. Published by Elsevier Inc.
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