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Enzyme therapy and immune response in relation to CRIM status: the Dutch experience in classic infantile Pompe disease.
J Inherit Metab Dis 2015; 38(2):305-14JI

Abstract

BACKGROUND

Enzyme-replacement therapy (ERT) in Pompe disease--an inherited metabolic disorder caused by acid α-glucosidase deficiency and characterized in infants by generalized muscle weakness and cardiomyopathy--can be complicated by immune responses. Infants that do not produce any endogenous acid α-glucosidase, so-called CRIM-negative patients, reportedly develop a strong response. We report the clinical outcome of our Dutch infants in relation to their CRIM status and immune response.

METHODS

Eleven patients were genotyped and their CRIM status was determined. Antibody formation and clinical outcome were assessed for a minimum of 4 years.

RESULTS

ERT was commenced between 0.1 and 8.3 months of age, and patients were treated from 0.3 to 13.7 years. All patients developed antibodies. Those with a high antibody titer (above 1:31,250) had a poor response. The antibody titers varied substantially between patients and did not strictly correlate with the patients' CRIM status. Patients who started ERT beyond 2 months of age tended to develop higher titers than those who started earlier. All three CRIM-negative patients in our study succumbed by the age of 4 years seemingly unrelated to the height of their antibody titer.

CONCLUSION

Antibody formation is a common response to ERT in classic infantile Pompe disease and counteracts the effect of treatment. The counteracting effect seems determined by the antibody:enzyme molecular stoichiometry. The immune response may be minimized by early start of ERT and by immune modulation, as proposed by colleagues. The CRIM-negative status itself seems associated with poor outcome.

Authors+Show Affiliations

Department of Pediatrics, Division of Metabolic Diseases and Genetics, Center for Lysosomal and Metabolic Diseases, Erasmus MC University Medical Center, Rotterdam, The Netherlands, carinvangelder@gmail.com.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24715333

Citation

van Gelder, Carin M., et al. "Enzyme Therapy and Immune Response in Relation to CRIM Status: the Dutch Experience in Classic Infantile Pompe Disease." Journal of Inherited Metabolic Disease, vol. 38, no. 2, 2015, pp. 305-14.
van Gelder CM, Hoogeveen-Westerveld M, Kroos MA, et al. Enzyme therapy and immune response in relation to CRIM status: the Dutch experience in classic infantile Pompe disease. J Inherit Metab Dis. 2015;38(2):305-14.
van Gelder, C. M., Hoogeveen-Westerveld, M., Kroos, M. A., Plug, I., van der Ploeg, A. T., & Reuser, A. J. (2015). Enzyme therapy and immune response in relation to CRIM status: the Dutch experience in classic infantile Pompe disease. Journal of Inherited Metabolic Disease, 38(2), pp. 305-14. doi:10.1007/s10545-014-9707-6.
van Gelder CM, et al. Enzyme Therapy and Immune Response in Relation to CRIM Status: the Dutch Experience in Classic Infantile Pompe Disease. J Inherit Metab Dis. 2015;38(2):305-14. PubMed PMID: 24715333.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Enzyme therapy and immune response in relation to CRIM status: the Dutch experience in classic infantile Pompe disease. AU - van Gelder,Carin M, AU - Hoogeveen-Westerveld,Marianne, AU - Kroos,Marian A, AU - Plug,Iris, AU - van der Ploeg,Ans T, AU - Reuser,Arnold J J, Y1 - 2014/04/09/ PY - 2013/11/15/received PY - 2014/03/12/accepted PY - 2014/01/30/revised PY - 2014/4/10/entrez PY - 2014/4/10/pubmed PY - 2016/3/5/medline SP - 305 EP - 14 JF - Journal of inherited metabolic disease JO - J. Inherit. Metab. Dis. VL - 38 IS - 2 N2 - BACKGROUND: Enzyme-replacement therapy (ERT) in Pompe disease--an inherited metabolic disorder caused by acid α-glucosidase deficiency and characterized in infants by generalized muscle weakness and cardiomyopathy--can be complicated by immune responses. Infants that do not produce any endogenous acid α-glucosidase, so-called CRIM-negative patients, reportedly develop a strong response. We report the clinical outcome of our Dutch infants in relation to their CRIM status and immune response. METHODS: Eleven patients were genotyped and their CRIM status was determined. Antibody formation and clinical outcome were assessed for a minimum of 4 years. RESULTS: ERT was commenced between 0.1 and 8.3 months of age, and patients were treated from 0.3 to 13.7 years. All patients developed antibodies. Those with a high antibody titer (above 1:31,250) had a poor response. The antibody titers varied substantially between patients and did not strictly correlate with the patients' CRIM status. Patients who started ERT beyond 2 months of age tended to develop higher titers than those who started earlier. All three CRIM-negative patients in our study succumbed by the age of 4 years seemingly unrelated to the height of their antibody titer. CONCLUSION: Antibody formation is a common response to ERT in classic infantile Pompe disease and counteracts the effect of treatment. The counteracting effect seems determined by the antibody:enzyme molecular stoichiometry. The immune response may be minimized by early start of ERT and by immune modulation, as proposed by colleagues. The CRIM-negative status itself seems associated with poor outcome. SN - 1573-2665 UR - https://www.unboundmedicine.com/medline/citation/24715333/Enzyme_therapy_and_immune_response_in_relation_to_CRIM_status:_the_Dutch_experience_in_classic_infantile_Pompe_disease_ L2 - https://doi.org/10.1007/s10545-014-9707-6 DB - PRIME DP - Unbound Medicine ER -