Type

Journal Article

Authors

Noel G McElvaney
Emer P Reeves
Pauline M Rudd
Martin Clynes
Michael Henry
Paula Meleady
Joanne Keenan
Tomás P Carroll
David A Bergin
M Emmet O'Brien
and 2 others

Subjects

Biochemistry

Topics
humans middle aged metabolism adult spectrometry fluorescence tandem mass spectrometry chromatography liquid polysaccharides chemistry electrophoresis gel two dimensional genetics alpha 1 antitrypsin fucose male mutation case control studies young adult alpha 1 antitrypsin deficiency

Increased outer arm and core fucose residues on the N-glycans of mutated alpha-1 antitrypsin protein from alpha-1 antitrypsin deficient individuals. (2013)

Abstract Alpha-1 antitrypsin (AAT) is the major physiological inhibitor of a range of serine proteases, and in the lung, it maintains a protease-antiprotease balance. AAT deficiency (AATD) is an autosomal co-dominant condition with the Z mutation being the most common cause. Individuals homozygous for Z (PiZZ) have low levels of circulating mutant Z-AAT protein leading to premature emphysematous lung disease. Extensive glycoanalysis has been performed on normal AAT (M-AAT) from healthy individuals and the importance of glycosylation in affecting the immune modulatory roles of AAT is documented. However, no glycoanalysis has been carried out on Z-AAT from deficient individuals to date. In this study, we investigate whether the glycans present on Z-AAT differ to those found on M-AAT from healthy controls. Plasma AAT was purified from 10 individuals: 5 AATD donors with the PiZZ phenotype and 5 PiMM healthy controls. Glycoanalysis was performed employing N-glycan release, exoglycosidase digestion and UPLC analysis. No difference in branched glycans was identified between AATD and healthy controls. However, a significant increase in both outer arm (α1-3) (p = 0.04) and core (α1-6) fucosylated glycans (p < 0.0001) was found on Z-AAT compared to M-AAT. This study has identified increased fucosylation on N-glycans of Z-AAT indicative of ongoing inflammation in AATD individuals with implications for early therapeutic intervention.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed

Full list of authors on original publication

Noel G McElvaney, Emer P Reeves, Pauline M Rudd, Martin Clynes, Michael Henry, Paula Meleady, Joanne Keenan, Tomás P Carroll, David A Bergin, M Emmet O'Brien and 2 others

Experts in our system

1
Noel G McElvaney
Royal College of Surgeons in Ireland
Total Publications: 190
 
2
Emer P Reeves
Royal College of Surgeons in Ireland
Total Publications: 58
 
3
Pauline M Rudd
University College Dublin
Total Publications: 43
 
4
Martin Clynes
Dublin City University
Total Publications: 209
 
5
Michael Henry
Dublin City University
Total Publications: 78
 
6
Paula Meleady
Dublin City University
Total Publications: 95
 
7
Joanne Keenan
Dublin City University
Total Publications: 23
 
8
Tomás P Carroll
Royal College of Surgeons in Ireland
Total Publications: 25
 
9
David A Bergin
Royal College of Surgeons in Ireland
Total Publications: 27
 
10
M Emmet O'Brien
Royal College of Surgeons in Ireland
Total Publications: 8