Anđelo Beletić1*, Irena Trbojević-Akmačić1, Jasminka Krištić1 and Gordan Lauc1,2
1 Genos Ltd, Glycoscience Research Laboratory, Zagreb, Croatia
2 Faculty of Pharmacy and Biochemistry, University of Zagreb, Zagreb, Croatia
abeletic [at] genos.hr
Abstract
Alpha-1 antitrypsin (AAT) is the serin protease archetype, with biological roles shedding from the neutrophil-derived protease activities control to a comprehensive innate immunity modulation via interactions with the numerous proteins, cytokines, and cells. UniProt Knowledgebase® reports three glycosylation sites for AAT, with attached N-glycans contributing to approximately 12% of the total molecular mass and having a crucial role in immunomodulatory activities. The PubMed database was searched for “alpha-1 antitrypsin” and “glycosylation” using the following filters: full text available, the publication date of 10 years, and the preprints excluded. The search retrieved 73 results, and after the content analysis by the authors, 60 remained relevant, six reviews and 54 original research articles. Most studies used human samples (24 used serum/plasma, 23 cell cultures, four cerebrospinal or other non-standard sample fluids, and three studies combined the different sample types). There were also two studies on animals and one on plant models. Analysis of AAT glycoforms was the core of lab methodology in 52 studies, while six studies analyzed the released glycans. Thirteen studies focused on analytical protocols’ development or optimization. The glycosylation-related AAT structural and functional properties were among the aims of 25 studies, while 10 papers assessed these features from a glycoengineering perspective. The pathophysiological mechanisms relating to AAT glycosylation features were studied in 10 papers, and 20 studies identified AAT glycoforms as biomarker candidates, mainly in the oncology field (pancreatic, liver, oral, and ovarian cancer). These pioneer data mining results indicate the availability of comprehensive data about AAT glycosylation, thereby establishing a solid basis for further scientific and innovation efforts.
Keywords: data mining, alpha-1 antitrypsin, glycosylation