{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T23:10:50Z","timestamp":1787613050113,"version":"build-2736575974"},"reference-count":45,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2020,8,12]],"date-time":"2020-08-12T00:00:00Z","timestamp":1597190400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Fabry Disease (FD) is a rare, X-linked, lysosomal storage disease that mainly causes renal, cardiac and cerebral complications. Enzyme replacement therapy (ERT) with recombinant alpha-galactosidase A is available, but approximately 50% of male patients with classical FD develop inhibiting anti-drug antibodies (iADAs) that lead to reduced biochemical responses and an accelerated loss of renal function. Once immunization has occurred, iADAs tend to persist and tolerization is hard to achieve. Here we developed a pre-treatment prediction model for iADA development in FD using existing data from 120 classical male FD patients from three European centers, treated with ERT. We found that nonsense and frameshift mutations in the \u03b1-galactosidase A gene (p = 0.05), higher plasma lysoGb3 at baseline (p &lt; 0.001) and agalsidase beta as first treatment (p = 0.006) were significantly associated with iADA development. Prediction performance of a Random Forest model, using multiple variables (AUC-ROC: 0.77) was compared to a logistic regression (LR) model using the three significantly associated variables (AUC-ROC: 0.77). The LR model can be used to determine iADA risk in individual FD patients prior to treatment initiation. This helps to determine in which patients adjusted treatment and\/or immunomodulatory regimes may be considered to minimize iADA development risk.<\/jats:p>","DOI":"10.3390\/ijms21165784","type":"journal-article","created":{"date-parts":[[2020,8,12]],"date-time":"2020-08-12T09:14:49Z","timestamp":1597223689000},"page":"5784","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Predicting the Development of Anti-Drug Antibodies against Recombinant alpha-Galactosidase A in Male Patients with Classical Fabry Disease"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4745-5718","authenticated-orcid":false,"given":"Sanne J.","family":"van der Veen","sequence":"first","affiliation":[{"name":"Department of Endocrinology and Metabolism, Amsterdam University Medical Centers (AUMC), University of Amsterdam, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1096-8563","authenticated-orcid":false,"given":"Wytze J.","family":"Vlietstra","sequence":"additional","affiliation":[{"name":"Department of Medical Informatics, Erasmus University, 3000 CA Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"van Dussen","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Amsterdam University Medical Centers (AUMC), University of Amsterdam, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7989-4910","authenticated-orcid":false,"given":"Andr\u00e9 B.P.","family":"van Kuilenburg","sequence":"additional","affiliation":[{"name":"Laboratory Genetic Metabolic Diseases, Amsterdam University Medical Centers (AUMC), University of Amsterdam, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0750-8790","authenticated-orcid":false,"given":"Marcel G. W.","family":"Dijkgraaf","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Data Science, Amsterdam University Medical Centers, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malte","family":"Lenders","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine D, and Interdisciplinary Fabry Center (IFAZ), University Hospital Muenster, D-48149 Muenster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Brand","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine D, and Interdisciplinary Fabry Center (IFAZ), University Hospital Muenster, D-48149 Muenster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Wanner","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, University Hospital W\u00fcrzburg, 97080 W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derralynn","family":"Hughes","sequence":"additional","affiliation":[{"name":"Department of Haematology, Royal Free London National Health Service Foundation Trust and University College London, London NW3 2QG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Perry M.","family":"Elliott","sequence":"additional","affiliation":[{"name":"Department of Cardiology, St. Bartholomew\u2019s Hospital and University College London, London EC1A 7BE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla E. M.","family":"Hollak","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Amsterdam University Medical Centers (AUMC), University of Amsterdam, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirjam","family":"Langeveld","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Amsterdam University Medical Centers (AUMC), University of Amsterdam, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,8,12]]},"reference":[{"key":"ref_1","unstructured":"Valle, D.L., Antonarakis, S., Ballabio, A., Beaudet, A.L., and Mitchell, G.A. (2016). \u03b1-Galactosidase A Deficiency: Fabry Disease. 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