دورية أكاديمية
Quantitative HLA-class-II/factor VIII (FVIII) peptidomic variation in dendritic cells correlates with the immunogenic potential of therapeutic FVIII proteins in hemophilia A
| العنوان: | Quantitative HLA-class-II/factor VIII (FVIII) peptidomic variation in dendritic cells correlates with the immunogenic potential of therapeutic FVIII proteins in hemophilia A |
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| المؤلفون: | Diego, VP, Luu, BW, Hofmann, M, Dinh, LV, Almeida, M, Powell, JS, Rajalingam, R, Peralta, JM, Kumar, S, Curran, JE, Sauna, ZE, Kellerman, R, Park, Y, Key, NS, Escobar, MA, Huy, H, Verhagen, AM, Williams-Blangero, S, Lehmann, PV, Maraskovsky, E, Blangero, J, Howard, TE |
| بيانات النشر: | WILEY |
| سنة النشر: | 2020 |
| المجموعة: | The University of Melbourne: Digital Repository |
| الوصف: | BACKGROUND: Plasma-derived (pd) or recombinant (r) therapeutic factor VIII proteins (FVIIIs) are infused to arrest/prevent bleeding in patients with hemophilia A (PWHA). However, FVIIIs are neutralized if anti-FVIII-antibodies (inhibitors) develop. Accumulating evidence suggests that pdFVIIIs with von Willebrand factor (VWF) are less immunogenic than rFVIIIs and that distinct rFVIIIs are differentially immunogenic. Since inhibitor development is T-helper-cell-dependent, human leukocyte antigen (HLA)-class-II (HLAcII) molecules constitute an important early determinant. OBJECTIVES: Use dendritic cell (DC)-protein processing/presentation assays with mass-spectrometric and peptide-proteomic analyses to quantify the DP-bound, DQ-bound, and DR-bound FVIII-derived peptides in individual HLAcII repertoires and compare the immunogenic potential of six distinct FVIIIs based on their measured peptide counts. PATIENTS/METHODS: Monocyte-derived DCs from normal donors and/or PWHA were cultured with either: Mix-rFVIII, a VWF-free equimolar mixture of a full-length (FL)-rFVIII [Advate® (Takeda)] and four distinct B-domain-deleted (BDD)-rFVIIIs [Xyntha® (Pfizer), NovoEight® (Novo-Nordisk), Nuwiq® (Octapharma), and Afstyla® (CSL Behring GmBH)]; a pdFVIII + pdVWF [Beriate® (CSL Behring GmBH)]; Advate ± pdVWF; Afstyla ± pdVWF; and Xyntha + pdVWF. RESULTS: We showed that (i) Beriate had a significantly lower immunogenic potential than Advate ± pdVWF, Afstyla - pdVWF, and Mix-rFVIII; (ii) distinct FVIIIs differed significantly in their immunogenic potential in that, in addition to (i), Afstyla + pdVWF had a significantly lower immunogenic potential than Beriate, while the immunogenic potential of Beriate was not significantly different from that of Xyntha + pdVWF; and (iii) rFVIIIs with pdVWF had significantly lower immunogenic potentials than the same rFVIIIs without pdVWF. CONCLUSIONS: Our results provide HLAcII peptidomic level explanations for several important clinical observations/issues including the differential ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 1538-7933 1538-7836 |
| العلاقة: | Diego, V. P., Luu, B. W., Hofmann, M., Dinh, L. V., Almeida, M., Powell, J. S., Rajalingam, R., Peralta, J. M., Kumar, S., Curran, J. E., Sauna, Z. E., Kellerman, R., Park, Y., Key, N. S., Escobar, M. A., Huy, H., Verhagen, A. M., Williams-Blangero, S., Lehmann, P. V. ,. Howard, T. E. (2020). Quantitative HLA-class-II/factor VIII (FVIII) peptidomic variation in dendritic cells correlates with the immunogenic potential of therapeutic FVIII proteins in hemophilia A. JOURNAL OF THROMBOSIS AND HAEMOSTASIS, 18 (1), pp.201-216. https://doi.org/10.1111/jth.14647Test.; http://hdl.handle.net/11343/275216Test |
| الإتاحة: | https://doi.org/10.1111/jth.14647Test http://hdl.handle.net/11343/275216Test |
| رقم الانضمام: | edsbas.18626B71 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 15387933 15387836 |
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