Plasma N-glycome composition associates with chronic low back pain

Irena Trbojević-Akmačić, Frano Vučković, Marija Vilaj, Andrea Skelin, Lennart C. Karssen, Jasminka Krištić, Julija Jurić, Ana Momčilović, Jelena Šimunović, Massimo Mangino, Manuela De Gregori, Maurizio Marchesini, Concetta Dagostino, Jerko Štambuk, Mislav Novokmet, Richard Rauck, Yurii S. Aulchenko, Dragan Primorac, Leonardo Kapural, Klaas Buyse & 5 others Dieter Mesotten, Frances M.K. Williams, Jan van Zundert, Massimo Allegri, Gordan Lauc

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Background: Low back pain (LBP) is the symptom of a group of syndromes with heterogeneous underlying mechanisms and molecular pathologies, making treatment selection and patient prognosis very challenging. Moreover, symptoms and prognosis of LBP are influenced by age, gender, occupation, habits, and psychological factors. LBP may be characterized by an underlying inflammatory process. Previous studies indicated a connection between inflammatory response and total plasma N-glycosylation. We wanted to identify potential changes in total plasma N-glycosylation pattern connected with chronic low back pain (CLBP), which could give an insight into the pathogenic mechanisms of the disease. Methods: Plasma samples of 1128 CLBP patients and 760 healthy controls were collected in clinical centers in Italy, Belgium and Croatia and used for N-glycosylation profiling by hydrophilic interaction ultra-performance liquid chromatography (HILIC-UPLC) after N-glycans release, fluorescent labeling and clean-up. Observed N-glycosylation profiles have been compared with a cohort of 126 patients with acute inflammation that underwent abdominal surgery. Results: We have found a statistically significant increase in the relative amount of high-branched (tri-antennary and tetra-antennary) N-glycan structures on CLBP patients’ plasma glycoproteins compared to healthy controls. Furthermore, relative amounts of disialylated and trisialylated glycan structures were increased, while high-mannose and glycans containing bisecting N-acetylglucosamine decreased in CLBP. Conclusions: Observed changes in CLBP on the plasma N-glycome level are consistent with N-glycosylation changes usually seen in chronic inflammation. General significance: To our knowledge, this is a first large clinical study on CLBP patients and plasma N-glycome providing a new glycomics perspective on potential disease pathology.

Original languageEnglish
Pages (from-to)2124-2133
Number of pages10
JournalBiochimica et Biophysica Acta - General Subjects
Volume1862
Issue number10
DOIs
Publication statusPublished - Oct 1 2018

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Glycosylation
Low Back Pain
Plasmas
Polysaccharides
Chemical analysis
Pathology
Acetylglucosamine
Liquid chromatography
Mannose
Glycomics
Surgery
Labeling
Inflammation
Glycoproteins
Croatia
Molecular Pathology
Belgium
Hydrophobic and Hydrophilic Interactions
Occupations
Liquid Chromatography

Keywords

  • Glycan biomarker
  • Low back pain
  • Plasma N-glycosylation
  • Retrospective study

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

Cite this

Trbojević-Akmačić, I., Vučković, F., Vilaj, M., Skelin, A., Karssen, L. C., Krištić, J., ... Lauc, G. (2018). Plasma N-glycome composition associates with chronic low back pain. Biochimica et Biophysica Acta - General Subjects, 1862(10), 2124-2133. https://doi.org/10.1016/j.bbagen.2018.07.003

Plasma N-glycome composition associates with chronic low back pain. / Trbojević-Akmačić, Irena; Vučković, Frano; Vilaj, Marija; Skelin, Andrea; Karssen, Lennart C.; Krištić, Jasminka; Jurić, Julija; Momčilović, Ana; Šimunović, Jelena; Mangino, Massimo; De Gregori, Manuela; Marchesini, Maurizio; Dagostino, Concetta; Štambuk, Jerko; Novokmet, Mislav; Rauck, Richard; Aulchenko, Yurii S.; Primorac, Dragan; Kapural, Leonardo; Buyse, Klaas; Mesotten, Dieter; Williams, Frances M.K.; van Zundert, Jan; Allegri, Massimo; Lauc, Gordan.

In: Biochimica et Biophysica Acta - General Subjects, Vol. 1862, No. 10, 01.10.2018, p. 2124-2133.

Research output: Contribution to journalArticle

Trbojević-Akmačić, I, Vučković, F, Vilaj, M, Skelin, A, Karssen, LC, Krištić, J, Jurić, J, Momčilović, A, Šimunović, J, Mangino, M, De Gregori, M, Marchesini, M, Dagostino, C, Štambuk, J, Novokmet, M, Rauck, R, Aulchenko, YS, Primorac, D, Kapural, L, Buyse, K, Mesotten, D, Williams, FMK, van Zundert, J, Allegri, M & Lauc, G 2018, 'Plasma N-glycome composition associates with chronic low back pain', Biochimica et Biophysica Acta - General Subjects, vol. 1862, no. 10, pp. 2124-2133. https://doi.org/10.1016/j.bbagen.2018.07.003
Trbojević-Akmačić I, Vučković F, Vilaj M, Skelin A, Karssen LC, Krištić J et al. Plasma N-glycome composition associates with chronic low back pain. Biochimica et Biophysica Acta - General Subjects. 2018 Oct 1;1862(10):2124-2133. https://doi.org/10.1016/j.bbagen.2018.07.003
Trbojević-Akmačić, Irena ; Vučković, Frano ; Vilaj, Marija ; Skelin, Andrea ; Karssen, Lennart C. ; Krištić, Jasminka ; Jurić, Julija ; Momčilović, Ana ; Šimunović, Jelena ; Mangino, Massimo ; De Gregori, Manuela ; Marchesini, Maurizio ; Dagostino, Concetta ; Štambuk, Jerko ; Novokmet, Mislav ; Rauck, Richard ; Aulchenko, Yurii S. ; Primorac, Dragan ; Kapural, Leonardo ; Buyse, Klaas ; Mesotten, Dieter ; Williams, Frances M.K. ; van Zundert, Jan ; Allegri, Massimo ; Lauc, Gordan. / Plasma N-glycome composition associates with chronic low back pain. In: Biochimica et Biophysica Acta - General Subjects. 2018 ; Vol. 1862, No. 10. pp. 2124-2133.
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abstract = "Background: Low back pain (LBP) is the symptom of a group of syndromes with heterogeneous underlying mechanisms and molecular pathologies, making treatment selection and patient prognosis very challenging. Moreover, symptoms and prognosis of LBP are influenced by age, gender, occupation, habits, and psychological factors. LBP may be characterized by an underlying inflammatory process. Previous studies indicated a connection between inflammatory response and total plasma N-glycosylation. We wanted to identify potential changes in total plasma N-glycosylation pattern connected with chronic low back pain (CLBP), which could give an insight into the pathogenic mechanisms of the disease. Methods: Plasma samples of 1128 CLBP patients and 760 healthy controls were collected in clinical centers in Italy, Belgium and Croatia and used for N-glycosylation profiling by hydrophilic interaction ultra-performance liquid chromatography (HILIC-UPLC) after N-glycans release, fluorescent labeling and clean-up. Observed N-glycosylation profiles have been compared with a cohort of 126 patients with acute inflammation that underwent abdominal surgery. Results: We have found a statistically significant increase in the relative amount of high-branched (tri-antennary and tetra-antennary) N-glycan structures on CLBP patients’ plasma glycoproteins compared to healthy controls. Furthermore, relative amounts of disialylated and trisialylated glycan structures were increased, while high-mannose and glycans containing bisecting N-acetylglucosamine decreased in CLBP. Conclusions: Observed changes in CLBP on the plasma N-glycome level are consistent with N-glycosylation changes usually seen in chronic inflammation. General significance: To our knowledge, this is a first large clinical study on CLBP patients and plasma N-glycome providing a new glycomics perspective on potential disease pathology.",
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AU - Trbojević-Akmačić, Irena

AU - Vučković, Frano

AU - Vilaj, Marija

AU - Skelin, Andrea

AU - Karssen, Lennart C.

AU - Krištić, Jasminka

AU - Jurić, Julija

AU - Momčilović, Ana

AU - Šimunović, Jelena

AU - Mangino, Massimo

AU - De Gregori, Manuela

AU - Marchesini, Maurizio

AU - Dagostino, Concetta

AU - Štambuk, Jerko

AU - Novokmet, Mislav

AU - Rauck, Richard

AU - Aulchenko, Yurii S.

AU - Primorac, Dragan

AU - Kapural, Leonardo

AU - Buyse, Klaas

AU - Mesotten, Dieter

AU - Williams, Frances M.K.

AU - van Zundert, Jan

AU - Allegri, Massimo

AU - Lauc, Gordan

PY - 2018/10/1

Y1 - 2018/10/1

N2 - Background: Low back pain (LBP) is the symptom of a group of syndromes with heterogeneous underlying mechanisms and molecular pathologies, making treatment selection and patient prognosis very challenging. Moreover, symptoms and prognosis of LBP are influenced by age, gender, occupation, habits, and psychological factors. LBP may be characterized by an underlying inflammatory process. Previous studies indicated a connection between inflammatory response and total plasma N-glycosylation. We wanted to identify potential changes in total plasma N-glycosylation pattern connected with chronic low back pain (CLBP), which could give an insight into the pathogenic mechanisms of the disease. Methods: Plasma samples of 1128 CLBP patients and 760 healthy controls were collected in clinical centers in Italy, Belgium and Croatia and used for N-glycosylation profiling by hydrophilic interaction ultra-performance liquid chromatography (HILIC-UPLC) after N-glycans release, fluorescent labeling and clean-up. Observed N-glycosylation profiles have been compared with a cohort of 126 patients with acute inflammation that underwent abdominal surgery. Results: We have found a statistically significant increase in the relative amount of high-branched (tri-antennary and tetra-antennary) N-glycan structures on CLBP patients’ plasma glycoproteins compared to healthy controls. Furthermore, relative amounts of disialylated and trisialylated glycan structures were increased, while high-mannose and glycans containing bisecting N-acetylglucosamine decreased in CLBP. Conclusions: Observed changes in CLBP on the plasma N-glycome level are consistent with N-glycosylation changes usually seen in chronic inflammation. General significance: To our knowledge, this is a first large clinical study on CLBP patients and plasma N-glycome providing a new glycomics perspective on potential disease pathology.

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KW - Plasma N-glycosylation

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