Irena Trbojević-Akmačić1, Frano Vučković2, Marija Vilaj3, Andrea Skelin4, Lennart C Karssen5, Jasminka Krištić6, Julija Jurić7, Ana Momčilović8, Jelena Šimunović9, Massimo Mangino10, Manuela De Gregori11, Maurizio Marchesini12, Concetta Dagostino13, Jerko Štambuk14, Mislav Novokmet15, Richard Rauck16, Yurii S Aulchenko17, Dragan Primorac18, Leonardo Kapural19, Klaas Buyse20, Dieter Mesotten21, Frances M K Williams22, Jan van Zundert23, Massimo Allegri24, Gordan Lauc25. 1. Genos Glycoscience Research Laboratory, Zagreb, Croatia. Electronic address: iakmacic@genos.hr. 2. Genos Glycoscience Research Laboratory, Zagreb, Croatia. Electronic address: fvuckovic@genos.hr. 3. Genos Glycoscience Research Laboratory, Zagreb, Croatia. Electronic address: mvilaj@genos.hr. 4. Genos Glycoscience Research Laboratory, Zagreb, Croatia; St. Catherine Specialty Hospital, Zabok/Zagreb, Croatia. Electronic address: askelin@genos.hr. 5. PolyOmica, Het Vlaggeschip 61, 5237 PA 's-Hertogenbosch, The Netherlands. Electronic address: l.c.karssen@polyomica.com. 6. Genos Glycoscience Research Laboratory, Zagreb, Croatia. Electronic address: jkristic@genos.hr. 7. Genos Glycoscience Research Laboratory, Zagreb, Croatia. Electronic address: jjuric@genos.hr. 8. Genos Glycoscience Research Laboratory, Zagreb, Croatia; The Glycomics and Glycoproteomics Group, Center for Proteomics and Metabolomics, Leiden University Medical Center, The Netherlands. Electronic address: a.momcilovic@lumc.nl. 9. Genos Glycoscience Research Laboratory, Zagreb, Croatia. Electronic address: jsimunovic@genos.hr. 10. Department of Twin Research and Genetic Epidemiology, King's College London, London, UK; NIHR Biomedical Research Centre at Guy's and St Thomas' Foundation Trust, London SE1 9RT, UK. Electronic address: massimo.mangino@kcl.ac.uk. 11. Pain Therapy Service, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; SIMPAR Group, Italy. Electronic address: manuela.degregori@unipv.it. 12. SIMPAR Group, Italy; Anesthesia, Intensive Care and Pain Service, Parma Hospital, Parma, Italy. Electronic address: mmarchesini@parmanesthesia.com. 13. SIMPAR Group, Italy; Department of Medicine and Surgery, University of Parma, Parma, Italy. Electronic address: cdagostino@parmanesthesia.com. 14. Genos Glycoscience Research Laboratory, Zagreb, Croatia. Electronic address: jstambuk@genos.hr. 15. Genos Glycoscience Research Laboratory, Zagreb, Croatia. Electronic address: mnovokmet@genos.hr. 16. Carolinas Pain Institute, Winston Salem, NC, USA. Electronic address: rrauck@ccrpain.com. 17. PolyOmica, Het Vlaggeschip 61, 5237 PA 's-Hertogenbosch, The Netherlands. Electronic address: y.s.aulchenko@polyomica.com. 18. St. Catherine Specialty Hospital, Zabok/Zagreb, Croatia; J J Strossmayer University of Osijek, School of Medicine, Osijek, Croatia; University of Split, School of Medicine, Split, Croatia; Eberly College of Science, The Pennsylvania State University, University Park, USA; Children's Hospital Srebrnjak, Zagreb, Croatia. Electronic address: draganprimorac2@gmail.com. 19. Carolinas Pain Institute, Winston Salem, NC, USA. Electronic address: lkapural@ccrpain.com. 20. Department of Anesthesiology and Multidisciplinary Pain Center, Ziekenhuis Oost-Limburg, Genk, Belgium. Electronic address: k.buysse@zol.be. 21. Department of Anesthesiology and Multidisciplinary Pain Center, Ziekenhuis Oost-Limburg, Genk, Belgium. Electronic address: d.mesotten@zol.be. 22. Department of Twin Research and Genetic Epidemiology, King's College London, London, UK. Electronic address: frances.williams@kcl.ac.uk. 23. Department of Anesthesiology and Multidisciplinary Pain Center, Ziekenhuis Oost-Limburg, Genk, Belgium. Electronic address: jan.vanzundert@zol.be. 24. SIMPAR Group, Italy; Anesthesia and Intensive Care Service - IRCCS MultiMedica Hospital, Sesto San Giovanni, Milano, Italy. Electronic address: massimo.allegri@unipr.it. 25. Genos Glycoscience Research Laboratory, Zagreb, Croatia; University of Zagreb, Faculty of Pharmacy and Biochemistry, Zagreb, Croatia. Electronic address: glauc@pharma.hr.
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.
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.
Authors: Sodbo Zh Sharapov; Yakov A Tsepilov; Lucija Klaric; Massimo Mangino; Gaurav Thareja; Alexandra S Shadrina; Mirna Simurina; Concetta Dagostino; Julia Dmitrieva; Marija Vilaj; Frano Vuckovic; Tamara Pavic; Jerko Stambuk; Irena Trbojevic-Akmacic; Jasminka Kristic; Jelena Simunovic; Ana Momcilovic; Harry Campbell; Margaret Doherty; Malcolm G Dunlop; Susan M Farrington; Maja Pucic-Bakovic; Christian Gieger; Massimo Allegri; Edouard Louis; Michel Georges; Karsten Suhre; Tim Spector; Frances M K Williams; Gordan Lauc; Yurii S Aulchenko Journal: Hum Mol Genet Date: 2019-06-15 Impact factor: 6.150