| Autor: |
Hanić M; Genos Glycoscience Research Laboratory, 10000 Zagreb, Croatia., Vučković F; Genos Glycoscience Research Laboratory, 10000 Zagreb, Croatia., Deriš H; Genos Glycoscience Research Laboratory, 10000 Zagreb, Croatia., Bewshea C; Exeter Inflammatory Bowel Disease and Pharmacogenetics Research Group, University of Exeter, Exeter EX4 4SB, UK., Lin S; Exeter Inflammatory Bowel Disease and Pharmacogenetics Research Group, University of Exeter, Exeter EX4 4SB, UK., Goodhand JR; Exeter Inflammatory Bowel Disease and Pharmacogenetics Research Group, University of Exeter, Exeter EX4 4SB, UK., Ahmad T; Exeter Inflammatory Bowel Disease and Pharmacogenetics Research Group, University of Exeter, Exeter EX4 4SB, UK., Trbojević-Akmačić I; Genos Glycoscience Research Laboratory, 10000 Zagreb, Croatia., Kennedy NA; Exeter Inflammatory Bowel Disease and Pharmacogenetics Research Group, University of Exeter, Exeter EX4 4SB, UK., Lauc G; Genos Glycoscience Research Laboratory, 10000 Zagreb, Croatia.; Faculty of Pharmacy and Biochemistry, University of Zagreb, 10000 Zagreb, Croatia. |
| Abstrakt: |
Crohn's disease (CD) is a chronic inflammation of the digestive tract that significantly impairs patients' quality of life and well-being. Anti-TNF biologicals revolutionised the treatment of CD, yet many patients do not adequately respond to such therapy. Previous studies have demonstrated a pro-inflammatory pattern in the composition of CD patients' immunoglobulin G (IgG) N-glycome compared to healthy individuals. Here, we utilised the high-throughput UHPLC method for N-glycan analysis to explore the longitudinal effect of the anti-TNF drugs infliximab and adalimumab on N-glycome composition of total serum IgG in 198 patients, as well as the predictive potential of IgG N-glycans at baseline to detect primary non-responders to anti-TNF therapy in 1315 patients. We discovered a significant decrease in IgG agalactosylation and an increase in monogalactosylation, digalactosylation and sialylation during the 14 weeks of anti-TNF treatment, regardless of therapy response, all of which suggested a diminished inflammatory environment in CD patients treated with anti-TNF therapy. Furthermore, we observed that IgG N-glycome might contain certain information regarding the anti-TNF therapy outcome before initiating the treatment. However, it is impossible to predict future primary non-responders to anti-TNF therapy based solely on IgG N-glycome composition at baseline. |
