The course of A alpha Val541 as a proteinase 3 specific neo-epitope after alpha-1-antitrypsin augmentation in severe deficient patients
| العنوان: | The course of A alpha Val541 as a proteinase 3 specific neo-epitope after alpha-1-antitrypsin augmentation in severe deficient patients |
|---|---|
| المؤلفون: | Dirk Jan A.R. Moes, Richard A Mumford, Jan Stolk, Pieter S. Hiemstra, Iris G.M. Schouten |
| المصدر: | International Journal of Molecular Sciences Volume 22 Issue 15 International Journal of Molecular Sciences, 22(15). MDPI International Journal of Molecular Sciences, Vol 22, Iss 8031, p 8031 (2021) |
| بيانات النشر: | MDPI, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Adult, Male, medicine.medical_specialty, Proteases, QH301-705.5, Myeloblastin, Population, Alpha (ethology), Gastroenterology, Severity of Illness Index, Catalysis, Article, Inorganic Chemistry, Epitopes, In vivo, Proteinase 3, Internal medicine, alpha 1-Antitrypsin Deficiency, Medicine, Humans, Fibrinopeptide, Physical and Theoretical Chemistry, Biology (General), education, Molecular Biology, QD1-999, Spectroscopy, education.field_of_study, Alpha 1-antitrypsin deficiency, business.industry, Organic Chemistry, Elastase, alpha-1-antitrypsin deficiency, alpha-1-antitrypsin augmentation therapy, General Medicine, Middle Aged, medicine.disease, Computer Science Applications, proteinase 3, Chemistry, alpha 1-Antitrypsin, biomarker, Female, business |
| الوصف: | In alpha-1-antitrypsin deficiency (AATD), neutrophil serine proteases such as elastase and proteinase 3 (PR3) are insufficiently inhibited. A previous study in AATD patients showed a higher plasma level of the specific PR3-generated fibrinogen-derived peptide AαVal541, compared with healthy controls. Here, we analyzed the course of AαVal541 plasma levels during 4 weeks after a single iv dose of 240 mg/kg AAT in ten patients with genotype Z/Rare or Rare/Rare. To this end, we developed an immunoassay to measure AαVal541 in plasma and applied population pharmacokinetic modeling for AAT. The median AαVal541 plasma level before treatment was 140.2 nM (IQR 51.5–234.8 nM)). In five patients who received AAT for the first time, AαVal541 levels decreased to 20.6 nM (IQR 5.8–88.9 nM), and in five patients who already had received multiple infusions before, it decreased to 26.2 nM (IQR 22.31–35.0 nM). In 9 of 10 patients, AαVal541 levels were reduced to the median level of healthy controls (21.4 nM IQR 16.7–30.1 nM). At 7–14 days after treatment, AαVal541 levels started to increase again in all patients. Our results show that fibrinopeptide AαVal541 may serve as a biochemical footprint to assess the efficacy of in vivo inhibition of PR3 activity in patients receiving intravenous AAT augmentation therapy. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fc47515c3028e6d18479b968e7ec3993Test https://hdl.handle.net/1887/3209147Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....fc47515c3028e6d18479b968e7ec3993 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |