Therefore, there is a need to standardize the protocol and the threshold retained to define inhibition. In summary, we cannot conclude that antibodies (not only neutralizing) are associated with clinical events in our cohort in this time-point study. Funding Not applicable. Availability of data and materials The datasets generated and/or analysed during the current study are not publicly available due to the individual persons data that are involved but are available from the corresponding author on reasonable request. Abbreviations ADAAnti-drug antibodiesERTEnzyme replacement therapy Authors contributions WM, OL and OB designed the study, performed the experiments, interpreted the data, drafted the manuscript and approved this final version. Notes Ethics approval and consent to participate Legal authorizations were obtained from the Comit consultatif sur le traitement de linformation en matire de recherche dans le domaine de la sant (n14.324bis) and the Comit de Protection des personnes Paris VI, according to the relevant French legislation. All patients signed written consent after specific oral and written information, for this research and its publication. Consent for publication All patients signed written consent after specific oral and written information, for this research and its publication. Competing interests Inserm U974 research team received financial support from Shire, AFM-Tlthon, SNFMI (Socit Nationale Fran?aise de Mdecine Interne) and VML (Vaincre les Maladies Lysosomales) for this study. Wladimir Mauhin: Travel fees and accommodations: Shire, Orphan Europe, Amicus, Sanofi-Genzyme, honorarium: Shire. Olivier Lidove: Travel fees, accommodations and honorarium: Shire, Sanofi-Genzyme; honorarium: Amicus. Olivier Benveniste: Travel fees Shire, LFB, CSL Behring; honorarium: Novartis, Neovacs, LFB. Publishers Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Contributor Information Wladimir Mauhin, Email: moc.liamg@nihuamdalw. Olivier Lidove, Email: gro.sscd-latipoh@evodilo. Olivier Benveniste, Email: rf.phpa@etsinevneb.reivilo.. antibodies developed in Fabry disease patients, a prospective analysis from the French multicenter cohort FFABRY [1, 2]. In the letter, our main message seems to have been eluded: the development of anti-drug antibodies (ADAs) depends on the clinical phenotype (ADA-positivity in classic patients 58.6% vs 6.7% in non-classic patients, p?p?=?0.7). There was also no difference in the mean infused Ospemifene dose received by patients during their whole exposure to ERT (ADA-positive vs ADA-negative patients 0.43?mg/kg vs 0.64?mg/kg, p?=?ns). We agree Ospemifene with Lenders and colleagues that purifying IgG subclasses could bring essential information concerning immunogenicity as a first approach. Also, it appears that this has not been performed in the referenced paper [3] where authors used purified total IgGs. We also agree with the authors that ADAs do not possess a mandatory neutralizing activity. This is the reason why we think that inhibition assays should only be performed Ospemifene after a first step using an immune-based assay such as an ELISA. Our goal was to study all ADAs, neutralizing and non-neutralizing. We may have to clarify that we did perform inhibition assay in all the men, contrary to what is pointed out in the letter. As expected, any of the antibody-negative serum was associated with enzymatic inhibition (Fig. 4a). It should also be reminded to readers that there is no consensus for inhibition assay and that the percentage of enzyme inhibition depends on the concentrations of ERT used in the protocol of the inhibition assay. Therefore, there is a need to standardize the protocol and the threshold retained to define inhibition. In summary, we cannot conclude that antibodies (not only neutralizing) are associated with clinical events in our cohort in this time-point study. Funding Not applicable. Availability of data and materials The datasets generated and/or analysed during the current study are not publicly available Mouse monoclonal to KRT15 due to the individual persons data that are involved but are available from the corresponding author on affordable request. Abbreviations ADAAnti-drug antibodiesERTEnzyme replacement therapy Authors contributions WM, OL and OB designed the study, performed the experiments, interpreted the data, drafted the manuscript and approved this final version. Notes Ethics Ospemifene approval and consent to participate Legal authorizations were obtained from the Comit consultatif sur le traitement de linformation en matire de recherche dans le domaine de la sant (n14.324bis) and the Comit de Protection des personnes Paris VI, according to the relevant French legislation. All patients signed written consent after specific oral and written information, for this research and its publication. Consent for publication All patients signed written consent after specific oral and written information, for this research and its publication. Competing interests Inserm U974 research team received financial support from Shire, AFM-Tlthon, SNFMI (Socit Nationale Fran?aise de Mdecine Interne) and VML (Vaincre les Maladies Lysosomales) for this study. Wladimir Mauhin: Travel fees and accommodations: Shire, Orphan Europe, Amicus, Sanofi-Genzyme, honorarium: Shire. Olivier Lidove: Travel fees, accommodations and honorarium: Shire, Sanofi-Genzyme; honorarium: Amicus. Olivier Benveniste: Travel fees Shire, LFB, CSL Behring; honorarium: Novartis, Neovacs, LFB. Publishers Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Contributor Information Wladimir Mauhin, Email: moc.liamg@nihuamdalw. Olivier Lidove, Email: gro.sscd-latipoh@evodilo. Olivier Benveniste, Email: rf.phpa@etsinevneb.reivilo..