{ "abstract": "(1) Background: Anti-drug antibodies (ADAs) may develop during enzyme replacement therapy (ERT) for Fabry disease and potentially affect biochemical response. Evidence have been derived mainly from males, while comparisons between agalsidase-alpha and agalsidase-beta remain limited by differences in ADA assays. The aim of the study is to evaluate ADA prevalence and titers in patients with Fabry disease treated with agalsidase-alpha or agalsidase-beta and to investigate associations with sex, GLA genotype, residual α-galactosidase A activity, and lyso-Gb3 levels. (2) Methods: This multicenter observational study included 117 patients with Fabry disease receiving ERT (50 males, 67 females), treated with agalsidase-alpha (n = 52) or agalsidase-beta (n = 65). ADAs were measured using an in-house enzyme-linked immunosorbent assay, and lyso-Gb3 by liquid chromatography–tandem mass spectrometry. GLA variants were centrally classified as predicted null-type or predicted non-null-type on the basis of the variant class, and α-galactosidase A activity at diagnosis was normalized to the lower limit of the assay reference interval. Multivariable regression analysis identified factors associated with ADA positivity and lyso-Gb3 levels. (3) Results: ADAs were detected in 55/117 patients. Positivity was more frequent in males than females, with no statistically significant difference between agalsidase-alpha and agalsidase-beta. Predicted null-type variants were associated with higher ADA positivity and titers, particularly in males. In multivariable models, male sex and predicted null-type variants independently predicted ADA positivity, whereas higher normalized α-galactosidase A activity was associated with lower odds. ADA positivity was not independently associated with lyso-Gb3. (4) Conclusions: ADA detection was primarily associated with male sex and predicted null-type GLA variants; no statistically significant association with the agalsidase administered was found. The high prevalence of binding ADAs in females warrants confirmation using orthogonal and functional assays.", "abstract_shown": true, "affiliations": [ "Immunoallergology Unit, Careggi University Hospital, 50134 Florence, Italy", "Laboratory of Molecular Genetics of Neurometabolic Diseases, Neuroscience and Human Genetics Department, Meyer Children’s Hospital IRCCS, 50134 Florence, Italy", "Department of Neurosciences, Psychology, Drug Research and Child Health (NEUROFARBA), University of Florence, 50139 Florence, Italy", "Unit of Nephrology, Dialysis and Transplantation, AOM-IRCCS Ospedale Policlinico San Martino, 16132 Genova, Italy", "Department of Internal Medicine and Medical Specialties (DIMI), University of Genoa, 16132 Genova, Italy", "Nephrology, Fondazione IRCCS San Gerardo dei Tintori, 20900 Monza, Italy", "School of Medicine and Surgery, University of Milano-Bicocca, 20126 Milan, Italy", "Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy", "Cardiomyopathy Unit, Careggi University Hospital, 50134 Florence, Italy", "Cardiology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Policlinico di Sant’Orsola, 40138 Bologna, Italy", "European Reference Network for Rare, Low Prevalence, and Complex Diseases of the Heart (ERN GUARD-Heart), 40138 Bologna, Italy", "Nephrology, Dialysis and Transplantation Unit, Careggi University Hospital, 50134 Florence, Italy", "NEUROFARBA Department, University of Florence, 50019 Florence, Italy", "Stroke Unit, Careggi University Hospital, 50134 Florence, Italy", "Nephrology and Dialysis Department, Belcolle Hospital, 01100 Viterbo, Italy", "SOSD Genetica Medica e Coordinamento Malattie Rare, Azienda Ospedaliero-Universitaria delle Marche, 60126 Ancona, Italy", "Unit of Nephrology, Azienda Socio-Sanitaria Territoriale (ASST) Papa Giovanni XXIII, 24127 Bergamo, Italy", "Newborn Screening, Clinical Biochemistry and Clinical Pharmacy Lab Meyer Children’s Hospital IRCCS, 50139 Florence, Italy", "Department of Experimental and Clinical Biomedical Sciences, University of Florence, 50134 Florence, Italy", "Divisione di Nefrologia e Dialisi Azienda Ospedaliera “G. Brotzu”, 09134 Cagliari, Italy", "Fondazione Policlinico Universitario Campus Bio-Medico, 00128 Rome, Italy" ], "article_type": null, "arxiv": null, "author_total": 29, "authors": [ { "affs": [ 0 ], "name": "Andrea Matucci" }, { "affs": [ 0 ], "name": "Michael Diomaiuti" }, { "affs": [ 1, 2 ], "name": "Amelia Morrone" }, { "affs": [ 3, 4 ], "name": "Pasquale Esposito", "orcid": "0000-0002-0834-5586" }, { "affs": [ 5, 6 ], "name": "Federico Pieruzzi", "orcid": "0000-0002-1302-6846" }, { "affs": [ 7, 8 ], "name": "Maurizio Pieroni", "orcid": "0000-0002-6830-4292" }, { "affs": [ 0, 7 ], "name": "Emanuele Vivarelli" }, { "affs": [ 9, 10 ], "name": "Elena Biagini", "orcid": "0000-0003-0295-0440" }, { "affs": [ 9, 10 ], "name": "Raffaello Ditaranto", "orcid": "0000-0001-7025-0679" }, { "affs": [ 9, 10 ], "name": "Maria Alessandra Schiavo", "orcid": "0009-0006-6644-9822" }, { "affs": [ 11 ], "name": "Calogero Lino Cirami" }, { "affs": [ 11 ], "name": "Leonardo Caroti" }, { "affs": [ 11 ], "name": "Egrina Dervishi" }, { "affs": [ 12 ], "name": "Ilaria Romani" }, { "affs": [ 12, 13 ], "name": "Cristina Sarti", "orcid": "0000-0002-8409-4782" }, { "affs": [ 14 ], "name": "Mario Mangeri" }, { "affs": [ 5 ], "name": "Barbara Trezzi" }, { "affs": [ 5 ], "name": "Letizia Roggero" }, { "affs": [ 15 ], "name": "Claudia Sgattoni" }, { "affs": [ 16 ], "name": "Alessia Gennarini" }, { "affs": [ 17, 18 ], "name": "Giancarlo la Marca" }, { "affs": [ 17 ], "name": "Giulia Forni", "orcid": "0009-0005-3158-0348" }, { "affs": [ 19 ], "name": "Giacomo Mascia" }, { "affs": [ 1 ], "name": "Marina Rinaldi", "orcid": "0009-0002-7307-1726" }, { "affs": [ 8 ], "name": "Annamaria Del Franco" }, { "affs": [ 8 ], "name": "Alessia Argirò" }, { "affs": [ 20 ], "name": "Sandro Feriozzi", "orcid": "0000-0001-8420-8447" }, { "affs": [ 7 ], "name": "Matteo Accinno", "orcid": "0009-0009-5968-6880" }, { "affs": [ 0, 7 ], "name": "Alessandra Vultaggio", "orcid": "0000-0002-8775-9217" } ], "bibtex": "https://research.draconitic.com/paper/cgceqpxzbvahh.bib", "cited_by": 0, "doi": "10.3390/cells15212015", "fulltext_url": null, "id": "cgceqpxzbvahh", "issns": [ "2073-4409" ], "landing_url": "https://www.mdpi.com/2073-4409/15/21/2015", "language": null, "licence": "CC-BY-4.0", "licence_label": "CC BY 4.0", "licence_source": "article", "licence_url": "https://creativecommons.org/licenses/by/4.0/", "metadata_licence": null, "native_subjects": [], "openalex": null, "pdf_url": null, "pmcid": null, "pmid": null, "published": "2026-11-05", "publisher": "MDPI AG", "ris": "https://research.draconitic.com/paper/cgceqpxzbvahh.ris", "sources": [ { "first_seen": "2026-11-06T00:21:15Z", "native_id": "10.3390/cells15212015", "source": "crossref", "url": "https://www.mdpi.com/2073-4409/15/21/2015" } ], "subjects": [ { "field": "biology", "origin": "issn:2073-4409", "subfield": "cell-biology" } ], "title": "Anti-Drug Antibodies in Patients with Fabry Disease Treated with Agalsidase-Alpha or -Beta: A Retrospective Italian Multicenter Study", "title_text": "Anti-Drug Antibodies in Patients with Fabry Disease Treated with Agalsidase-Alpha or -Beta: A Retrospective Italian Multicenter Study", "type": "peer-reviewed", "updated_at": "2026-11-07T00:21:13Z", "url": "https://research.draconitic.com/paper/cgceqpxzbvahh", "venue": "Cells", "versions": [] }