{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T04:05:19Z","timestamp":1793505919444,"version":"4.5.0"},"reference-count":59,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,9,19]],"date-time":"2023-09-19T00:00:00Z","timestamp":1695081600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Prinses Beatrix Spierfonds","award":["09150161910230"],"award-info":[{"award-number":["09150161910230"]}]},{"name":"Prinses Beatrix Spierfonds","award":["LSHM16008"],"award-info":[{"award-number":["LSHM16008"]}]},{"DOI":"10.13039\/501100001826","name":"Netherlands Organization for Health Research and Development","doi-asserted-by":"publisher","award":["09150161910230"],"award-info":[{"award-number":["09150161910230"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001826","name":"Netherlands Organization for Health Research and Development","doi-asserted-by":"publisher","award":["LSHM16008"],"award-info":[{"award-number":["LSHM16008"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]},{"name":"TKI-program Life Sciences &amp; Health","award":["09150161910230"],"award-info":[{"award-number":["09150161910230"]}]},{"name":"TKI-program Life Sciences &amp; Health","award":["LSHM16008"],"award-info":[{"award-number":["LSHM16008"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Background: Pompe disease is a lysosomal storage disease characterised by skeletal and respiratory muscle weakness. Since 2006, enzyme replacement therapy (ERT) with alglucosidase alfa has been available. ERT significantly improves the prognosis of patients with Pompe disease. The effect of high antibody titres on treatment response in adults with late-onset Pompe disease (LOPD) remains unclear but may contribute to interpatient variation. We therefore conducted a systematic review on this subject. Methods: A systematic search was performed in Embase, Medline Ovid, Web of Science, Psych Info Ovid, Cochrane (Clinical Trials only), and Google Scholar (random top-200). Articles were included if they involved adults with LOPD treated with alglucosidase alfa and mentioned anti-rhGAA antibodies or antibody titres. In addition, articles mentioning dosages different from the standard recommended dosage were included. Results: Our literature search retrieved 2562 publications, and 17 fulfilled our selection criteria, describing 443 cases. Seven publications reported on anti-rhGAA antibody titres on a group level, with the percentage of patients with a high titre as defined in the included articles ranging from 0\u201333%. Six publications reported on the effect of anti-rhGAA antibody titre on clinical course, and four found no correlation. Two studies reported a negative effect on treatment. The first study found a greater improvement in Medical Research Council (MRC) score in patients with no detectable antibody titre. In the second study, a patient discontinued ERT due to a declining neuromuscular state as a result of high anti-rhGAA antibody titres. Seven publications reported on 17 individual patients with a high antibody titre (range 1:12,800\u20131:3,906,250). In only two cases were high-sustained neutralising antibodies reported to interfere with treatment efficacy. Conclusions: No clear effect of anti-rhGAA IgG antibodies on treatment response could be established for the majority of LOPD patients with a high antibody titre. In a minority of patients, a clinical decline related to (possible) interference of anti-rhGAA antibodies was described.<\/jats:p>","DOI":"10.3390\/biom13091414","type":"journal-article","created":{"date-parts":[[2023,9,19]],"date-time":"2023-09-19T23:11:52Z","timestamp":1695165112000},"page":"1414","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Are Anti-rhGAA Antibodies a Determinant of Treatment Outcome in Adults with Late-Onset Pompe Disease? A Systematic Review"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2377-3108","authenticated-orcid":false,"given":"Imke A. M.","family":"Ditters","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Center for Lysosomal and Metabolic Diseases, Erasmus MC, Erasmus University Medical Center, P.O. Box 2060, 3000 CB Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harmke A.","family":"van Kooten","sequence":"additional","affiliation":[{"name":"Department of Neurology, Center for Lysosomal and Metabolic Diseases, Erasmus MC, Erasmus University Medical Center, P.O. Box 2060, 3000 CB Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadine A. M. E.","family":"van der Beek","sequence":"additional","affiliation":[{"name":"Department of Neurology, Center for Lysosomal and Metabolic Diseases, Erasmus MC, Erasmus University Medical Center, P.O. Box 2060, 3000 CB Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ans T.","family":"van der Ploeg","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Center for Lysosomal and Metabolic Diseases, Erasmus MC, Erasmus University Medical Center, P.O. Box 2060, 3000 CB Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1276-0931","authenticated-orcid":false,"given":"Hidde H.","family":"Huidekoper","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Center for Lysosomal and Metabolic Diseases, Erasmus MC, Erasmus University Medical Center, P.O. Box 2060, 3000 CB Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8091-263X","authenticated-orcid":false,"given":"Johanna M. P.","family":"van den Hout","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Center for Lysosomal and Metabolic Diseases, Erasmus MC, Erasmus University Medical Center, P.O. Box 2060, 3000 CB Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1342","DOI":"10.1016\/S0140-6736(08)61555-X","article-title":"Pompe\u2019s disease","volume":"372","author":"Reuser","year":"2008","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2365","DOI":"10.1212\/WNL.0000000000004711","article-title":"Long-term benefit of enzyme replacement therapy in Pompe disease: A 5-year prospective study","volume":"89","author":"Kuperus","year":"2017","journal-title":"Neurology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1007\/s10545-012-9451-8","article-title":"36 months observational clinical study of 38 adult Pompe disease patients under alglucosidase alfa enzyme replacement therapy","volume":"35","author":"Regnery","year":"2012","journal-title":"J. Inherit. 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