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CRIM-negative infantile Pompe disease: characterization of immune responses in patients treated with ERT monotherapy.

Publication ,  Journal Article
Berrier, KL; Kazi, ZB; Prater, SN; Bali, DS; Goldstein, J; Stefanescu, MC; Rehder, CW; Botha, EG; Ellaway, C; Bhattacharya, K; Karabul, N ...
Published in: Genet Med
November 2015

PURPOSE: Enzyme replacement therapy (ERT) with recombinant human acid α-glucosidase (rhGAA) prolongs survival in infantile Pompe disease (IPD). However, the majority of cross-reactive immunologic material (CRIM)-negative (CN) patients have immune responses with significant clinical decline despite continued ERT. We aimed to characterize immune responses in CN patients with IPD receiving ERT monotherapy. METHODS: A chart review identified 20 CN patients with IPD treated with ERT monotherapy for ≥6 months. Patients were stratified by anti-rhGAA antibody titers: high sustained antibody titers (HSAT; ≥51,200) at least twice; low titers (LT; <6,400) throughout treatment; or sustained intermediate titers (SIT; 6,400-25,600). RESULTS: Despite early initiation of treatment, the majority (85%) of CN patients developed significant antibody titers, most with HSAT associated with invasive ventilation and death. Nearly all patients with HSAT had at least one nonsense GAA mutation, whereas the LT group exclusively carried splice-site or frameshift mutations. Only one patient in the HSAT group is currently alive after successful immune modulation in the entrenched setting. CONCLUSION: Immunological responses are a significant risk in CN IPD; thus induction of immune tolerance in the naive setting should strongly be considered. Further exploration of factors influencing immune responses is required, particularly with the advent of newborn screening for Pompe disease.

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Published In

Genet Med

DOI

EISSN

1530-0366

Publication Date

November 2015

Volume

17

Issue

11

Start / End Page

912 / 918

Location

United States

Related Subject Headings

  • alpha-Glucosidases
  • Treatment Outcome
  • Mutation
  • Male
  • Kaplan-Meier Estimate
  • Isoantibodies
  • Infant, Newborn
  • Infant
  • Immunoglobulin G
  • Humans
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Berrier, K. L., Kazi, Z. B., Prater, S. N., Bali, D. S., Goldstein, J., Stefanescu, M. C., … Kishnani, P. S. (2015). CRIM-negative infantile Pompe disease: characterization of immune responses in patients treated with ERT monotherapy. Genet Med, 17(11), 912–918. https://doi.org/10.1038/gim.2015.6
Berrier, Kathryn L., Zoheb B. Kazi, Sean N. Prater, Deeksha S. Bali, Jennifer Goldstein, Mihaela C. Stefanescu, Catherine W. Rehder, et al. “CRIM-negative infantile Pompe disease: characterization of immune responses in patients treated with ERT monotherapy.Genet Med 17, no. 11 (November 2015): 912–18. https://doi.org/10.1038/gim.2015.6.
Berrier KL, Kazi ZB, Prater SN, Bali DS, Goldstein J, Stefanescu MC, et al. CRIM-negative infantile Pompe disease: characterization of immune responses in patients treated with ERT monotherapy. Genet Med. 2015 Nov;17(11):912–8.
Berrier, Kathryn L., et al. “CRIM-negative infantile Pompe disease: characterization of immune responses in patients treated with ERT monotherapy.Genet Med, vol. 17, no. 11, Nov. 2015, pp. 912–18. Pubmed, doi:10.1038/gim.2015.6.
Berrier KL, Kazi ZB, Prater SN, Bali DS, Goldstein J, Stefanescu MC, Rehder CW, Botha EG, Ellaway C, Bhattacharya K, Tylki-Szymanska A, Karabul N, Rosenberg AS, Kishnani PS. CRIM-negative infantile Pompe disease: characterization of immune responses in patients treated with ERT monotherapy. Genet Med. 2015 Nov;17(11):912–918.

Published In

Genet Med

DOI

EISSN

1530-0366

Publication Date

November 2015

Volume

17

Issue

11

Start / End Page

912 / 918

Location

United States

Related Subject Headings

  • alpha-Glucosidases
  • Treatment Outcome
  • Mutation
  • Male
  • Kaplan-Meier Estimate
  • Isoantibodies
  • Infant, Newborn
  • Infant
  • Immunoglobulin G
  • Humans