Plasma N-glycome composition associates with chronic low back pain

• Published in: Biochimica et biophysica acta. General subjects Vol. 1862; no. 10; pp. 2124 - 2133
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.10.2018
• Subjects: Belgium; Croatia; fluorescent labeling; gender; Glycan biomarker; glycomics; glycoproteins; glycosylation; inflammation; Italy; Low back pain; N-acetylglucosamine; pain; patients; Plasma N-glycosylation; polysaccharides; prognosis; psychosocial factors; Retrospective study; ultra-performance liquid chromatography; Belgium; Italy; Croatia; S3; CRO; S4; B; DMSO; HM; Low back pain; IgG; G0; Retrospective study; G1; 2-AB; G2; G3; G4; LDD; AbSur; ANCOVA; FDR; GlcNAc; LBP; ADCC; PBS; META; ACE; SDS; HILIC-SPE; MS; BEL; CLBP; Glycan biomarker; GPs; GU; Area; Plasma N-glycosylation; UPLC; LB; ITA; HILIC-UPLC; 2-PB; HB; FA; S0; S1; S2
• ISSN: 0304-4165; 1872-8006
• DOI: 10.1016/j.bbagen.2018.07.003

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. 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. 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. Observed changes in CLBP on the plasma N-glycome level are consistent with N-glycosylation changes usually seen in chronic inflammation. 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. [Display omitted] •Relative occurrences of high-branched plasma N-glycans are increased in chronic low back pain.•Plasma protein N-glycosylation changes are consistent with chronic inflammation.•Relative occurrences of disialylated and trisialylated glycans change in chronic low back pain.•Specific glycan changes have a potential as biomarker for chronic low back pain.