{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T23:10:35Z","timestamp":1787613035521,"version":"build-2736575974"},"reference-count":32,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JASN"],"published-print":{"date-parts":[[2018,12]]},"abstract":"\n Background<\/jats:title>\n \n Use of enzyme replacement therapy (ERT) to treat Fabry disease, caused by deficient lysosomal\n \u03b1<\/jats:italic>\n -galactosidase A activity, can lead to formation of neutralizing antidrug antibodies (ADAs). These antibodies are associated with increased accumulation of plasma globotriaosylceramide (Gb3) and disease progression. Because agalsidase ERT can saturate ADA-binding sites during infusions (achieving agalsidase\/antibody equilibrium), we investigated in this open cohort study whether saturated patients (who have excess agalsidase after infusions) experience better clinical outcomes compared with not saturated patients (who have excess ADAs after infusions).\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n We isolated ADAs from sera of 26 men with Fabry disease receiving ERT (for a median of 94 months) and determined the amount of agalsidase necessary for antibody saturation. Clinical and biochemical outcomes included measurements of eGFR, interventricular septum thickness, and lyso-Gb3.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n ADA titers decreased significantly in all patients during infusion. Agalsidase-\n \u03b1<\/jats:italic>\n and agalsidase-\n \u03b2<\/jats:italic>\n had similar ADA-binding capacity and comparable ADA saturation frequency. Fourteen patients with saturated ADAs presented with mild (but significant) loss of eGFR, stable septum thickness, and significantly decreased lyso-Gb3 levels. The 12 not saturated patients had a more pronounced and significant loss of eGFR, increased septum thickness, and a smaller, nonsignificant reduction in lyso-Gb3, over time. In three patients, dose escalation resulted in partially elevated ADA titers, but importantly, also in reduced lyso-Gb3 levels.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n A not saturated ADA status during infusion is associated with progressive loss of eGFR and ongoing cardiac hypertrophy. Dose escalation can result in saturation of ADAs and decreasing lyso-Gb3 levels, but may lead to increased ADA titers.<\/jats:p>\n <\/jats:sec>","DOI":"10.1681\/asn.2018070740","type":"journal-article","created":{"date-parts":[[2018,11,1]],"date-time":"2018-11-01T12:25:59Z","timestamp":1541075159000},"page":"2879-2889","source":"Crossref","is-referenced-by-count":68,"title":["Dose-Dependent Effect of Enzyme Replacement Therapy on Neutralizing Antidrug Antibody Titers and Clinical Outcome in Patients with Fabry Disease"],"prefix":"10.1681","volume":"29","author":[{"given":"Malte","family":"Lenders","sequence":"first","affiliation":[{"name":"Internal Medicine D, Department of Nephrology, Hypertension and Rheumatology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leon Paul","family":"Neu\u00dfer","sequence":"additional","affiliation":[{"name":"Internal Medicine D, Department of Nephrology, Hypertension and Rheumatology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Rudnicki","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine IV \u2013 Nephrology and Hypertension, Medical University Innsbruck, Innsbruck, Austria;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Nordbeck","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, Comprehensive Heart Failure Center, and Fabry Center for Interdisciplinary Therapy, University Hospital and University of Wuerzburg, Wuerzburg, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sima","family":"Canaan-K\u00fchl","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Charit\u00e9 Universit\u00e4tsmedizin Berlin, Berlin, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albina","family":"Nowak","sequence":"additional","affiliation":[{"name":"University Heart Center, Cardiology Department, University Hospital of Zurich and University of Zurich, Zurich, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Cybulla","sequence":"additional","affiliation":[{"name":"Center of Internal Medicine, Department of Nephrology and Rheumatology, Fachinternistische Gemeinschaftspraxis Markgraeflerland, Muellheim, Germany; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boris","family":"Schmitz","sequence":"additional","affiliation":[{"name":"Institute of Sports Medicine, Molecular Genetics of Cardiovascular Disease, University Hospital Muenster, Muenster, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Lukas","sequence":"additional","affiliation":[{"name":"Albrecht Kossel Institute for Neuroregeneration, University Rostock Medical Center, Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Wanner","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, Comprehensive Heart Failure Center, and Fabry Center for Interdisciplinary Therapy, University Hospital and University of Wuerzburg, Wuerzburg, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan-Martin","family":"Brand","sequence":"additional","affiliation":[{"name":"Institute of Sports Medicine, Molecular Genetics of Cardiovascular Disease, University Hospital Muenster, Muenster, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Brand","sequence":"additional","affiliation":[{"name":"Internal Medicine D, Department of Nephrology, Hypertension and Rheumatology 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