Anti-TNF Biologicals Enhance the Anti-Inflammatory Properties of IgG N-Glycome in Crohn's Disease

Maja Hanić, Frano Vučković, Helena Deriš, Claire M. Bewshea, Simeng Lin, James R. Goodhand, Tariq Ahmad, Irena Trbojević-Akmačić, Nicholas A. Kennedy, Gordan Lauc (Lead / Corresponding author),

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Abstract

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 apro-inflammatory pattern in the composition of CD patients’ immunoglobulin G (IgG) N-glycomecompared 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 adalimumabon N-glycome composition of total serum IgG in 198 patients, as well as the predictive potential ofIgG N-glycans at baseline to detect primary non-responders to anti-TNF therapy in 1315 patients. Wediscovered a significant decrease in IgG agalactosylation and an increase in monogalactosylation,digalactosylation and sialylation during the 14 weeks of anti-TNF treatment, regardless of therapyresponse, all of which suggested a diminished inflammatory environment in CD patients treated withanti-TNF therapy. Furthermore, we observed that IgG N-glycome might contain certain informationregarding 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-glycomecomposition at baseline.
Original languageEnglish
Article number954
Number of pages13
JournalBiomolecules
Volume13
Issue number6
DOIs
Publication statusPublished - 7 Jun 2023

Keywords

  • Crohn’s disease
  • IgG glycosylation
  • infliximab
  • adalimumab
  • PANTS study

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