Antibodies against recombinant human alpha-glucosidase do not seem to affect clinical outcome in childhood onset Pompe disease
Abstract Background Enzyme replacement therapy (ERT) with recombinant human alpha-glucosidase (rhGAA, alglucosidase alfa) has improved survival, motor outcomes, daily life activity and quality of life in Pompe patients. However, ERT in Pompe disease often induces formation of antibodies, which may r...
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| Format: | Article |
| Language: | English |
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BMC
2022-02-01
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| Series: | Orphanet Journal of Rare Diseases |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13023-022-02175-2 |
| _version_ | 1818500871253655552 |
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| author | Harmke A. van Kooten Imke A. M. Ditters Marianne Hoogeveen-Westerveld Edwin H. Jacobs Johanna M. P. van den Hout Pieter A. van Doorn W. W. M. Pim Pijnappel Ans T. van der Ploeg Nadine A. M. E. van der Beek |
| author_facet | Harmke A. van Kooten Imke A. M. Ditters Marianne Hoogeveen-Westerveld Edwin H. Jacobs Johanna M. P. van den Hout Pieter A. van Doorn W. W. M. Pim Pijnappel Ans T. van der Ploeg Nadine A. M. E. van der Beek |
| author_sort | Harmke A. van Kooten |
| collection | DOAJ |
| description | Abstract Background Enzyme replacement therapy (ERT) with recombinant human alpha-glucosidase (rhGAA, alglucosidase alfa) has improved survival, motor outcomes, daily life activity and quality of life in Pompe patients. However, ERT in Pompe disease often induces formation of antibodies, which may reduce the efficacy of treatment and can lead to adverse events. In this study antibody formation and their effect on clinical outcome in patients with childhood onset Pompe disease treated with enzyme replacement therapy (ERT) with recombinant human alpha-glucosidase (rhGAA) are analyzed. Methods Enzyme-linked immunosorbent assay (ELISA) was used to determine anti-rhGAA antibody titers at predefined time points. The effect of antibodies on rhGAA activity (neutralizing effects) was measured in vitro. Clinical effects were evaluated by assessing muscle strength (MRC score) and function (QMFT-score), pulmonary function and infusion associated reactions (IARs). Results Twenty-two patients were included (age at start ERT 1.1–16.4 years, median treatment duration 12.4 years). Peak antibody titers were low (< 1:1250) in 9%, intermediate (1:1250–1:31,250) in 68% and high (≥ 1:31250) in 23% of patients; three patients (14%) had more than one titer of ≥ 1:31,250. Four patients (18%) experienced IARs; two patients from the high titer group had 86% of all IARs. Inhibition of intracellular GAA activity (58%) in vitro was found in one sample. The clinical course did not appear to be influenced by antibody titers. Conclusions Ninety-one percent of childhood onset Pompe patients developed anti-rhGAA antibodies (above background level), a minority of whom had high antibody titers at repeated time points, which do not seem to interfere with clinical outcome. High antibody titers may be associated with the occurrence of IARs. Although the majority of patients does not develop high titers; antibody titers should be determined in case of clinical deterioration. |
| first_indexed | 2024-12-10T20:48:33Z |
| format | Article |
| id | doaj.art-cdbdc84961404c50b4089ea2e7a833db |
| institution | Directory Open Access Journal |
| issn | 1750-1172 |
| language | English |
| last_indexed | 2024-12-10T20:48:33Z |
| publishDate | 2022-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Orphanet Journal of Rare Diseases |
| spelling | doaj.art-cdbdc84961404c50b4089ea2e7a833db2022-12-22T01:34:10ZengBMCOrphanet Journal of Rare Diseases1750-11722022-02-0117111310.1186/s13023-022-02175-2Antibodies against recombinant human alpha-glucosidase do not seem to affect clinical outcome in childhood onset Pompe diseaseHarmke A. van Kooten0Imke A. M. Ditters1Marianne Hoogeveen-Westerveld2Edwin H. Jacobs3Johanna M. P. van den Hout4Pieter A. van Doorn5W. W. M. Pim Pijnappel6Ans T. van der Ploeg7Nadine A. M. E. van der Beek8Department of Neurology, Center for Lysosomal and Metabolic Diseases, Erasmus MC, University Medical Center RotterdamDepartment of Pediatrics, Center for Lysosomal and Metabolic Diseases, Erasmus MC - Sophia Children’s Hospital, University Medical Center RotterdamDepartment of Pediatrics, Department of Clinical Genetics, Center for Lysosomal and Metabolic Diseases, Erasmus MC, University Medical CenterDepartment of Pediatrics, Department of Clinical Genetics, Center for Lysosomal and Metabolic Diseases, Erasmus MC, University Medical CenterDepartment of Pediatrics, Center for Lysosomal and Metabolic Diseases, Erasmus MC - Sophia Children’s Hospital, University Medical Center RotterdamDepartment of Neurology, Center for Lysosomal and Metabolic Diseases, Erasmus MC, University Medical Center RotterdamDepartment of Pediatrics, Department of Clinical Genetics, Center for Lysosomal and Metabolic Diseases, Erasmus MC, University Medical CenterDepartment of Pediatrics, Center for Lysosomal and Metabolic Diseases, Erasmus MC - Sophia Children’s Hospital, University Medical Center RotterdamDepartment of Neurology, Center for Lysosomal and Metabolic Diseases, Erasmus MC, University Medical Center RotterdamAbstract Background Enzyme replacement therapy (ERT) with recombinant human alpha-glucosidase (rhGAA, alglucosidase alfa) has improved survival, motor outcomes, daily life activity and quality of life in Pompe patients. However, ERT in Pompe disease often induces formation of antibodies, which may reduce the efficacy of treatment and can lead to adverse events. In this study antibody formation and their effect on clinical outcome in patients with childhood onset Pompe disease treated with enzyme replacement therapy (ERT) with recombinant human alpha-glucosidase (rhGAA) are analyzed. Methods Enzyme-linked immunosorbent assay (ELISA) was used to determine anti-rhGAA antibody titers at predefined time points. The effect of antibodies on rhGAA activity (neutralizing effects) was measured in vitro. Clinical effects were evaluated by assessing muscle strength (MRC score) and function (QMFT-score), pulmonary function and infusion associated reactions (IARs). Results Twenty-two patients were included (age at start ERT 1.1–16.4 years, median treatment duration 12.4 years). Peak antibody titers were low (< 1:1250) in 9%, intermediate (1:1250–1:31,250) in 68% and high (≥ 1:31250) in 23% of patients; three patients (14%) had more than one titer of ≥ 1:31,250. Four patients (18%) experienced IARs; two patients from the high titer group had 86% of all IARs. Inhibition of intracellular GAA activity (58%) in vitro was found in one sample. The clinical course did not appear to be influenced by antibody titers. Conclusions Ninety-one percent of childhood onset Pompe patients developed anti-rhGAA antibodies (above background level), a minority of whom had high antibody titers at repeated time points, which do not seem to interfere with clinical outcome. High antibody titers may be associated with the occurrence of IARs. Although the majority of patients does not develop high titers; antibody titers should be determined in case of clinical deterioration.https://doi.org/10.1186/s13023-022-02175-2AntibodiesEnzyme replacement therapyPompe diseaseRecombinant human alpha-glucosidase |
| spellingShingle | Harmke A. van Kooten Imke A. M. Ditters Marianne Hoogeveen-Westerveld Edwin H. Jacobs Johanna M. P. van den Hout Pieter A. van Doorn W. W. M. Pim Pijnappel Ans T. van der Ploeg Nadine A. M. E. van der Beek Antibodies against recombinant human alpha-glucosidase do not seem to affect clinical outcome in childhood onset Pompe disease Orphanet Journal of Rare Diseases Antibodies Enzyme replacement therapy Pompe disease Recombinant human alpha-glucosidase |
| title | Antibodies against recombinant human alpha-glucosidase do not seem to affect clinical outcome in childhood onset Pompe disease |
| title_full | Antibodies against recombinant human alpha-glucosidase do not seem to affect clinical outcome in childhood onset Pompe disease |
| title_fullStr | Antibodies against recombinant human alpha-glucosidase do not seem to affect clinical outcome in childhood onset Pompe disease |
| title_full_unstemmed | Antibodies against recombinant human alpha-glucosidase do not seem to affect clinical outcome in childhood onset Pompe disease |
| title_short | Antibodies against recombinant human alpha-glucosidase do not seem to affect clinical outcome in childhood onset Pompe disease |
| title_sort | antibodies against recombinant human alpha glucosidase do not seem to affect clinical outcome in childhood onset pompe disease |
| topic | Antibodies Enzyme replacement therapy Pompe disease Recombinant human alpha-glucosidase |
| url | https://doi.org/10.1186/s13023-022-02175-2 |
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