Identification of Chitinase-3-Like Protein 1 as a Novel Neutrophil Antigenic Target in Crohn's Disease

Claudia Deutschmann, Mandy Sowa, Jayaseelan Murugaiyan, Uwe Roesler, Nadja Röber, Karsten Conrad, Martin W. Laass, Dimitrios Bogdanos, Nora Sipeki, Maria Papp, Stefan Rödiger, Dirk Roggenbuck, Peter Schierack

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4 Citations (Scopus)

Abstract

Background and Aims: There is an increasing incidence of inflammatory bowel disease [IBD]. Autoimmune responses are involved in the pathophysiology of IBD, but their underlying pathways and target antigens have not yet been fully elucidated. Methods: Autoantigenic targets in IBD were identified after separation of whole cell proteins isolated from neutrophils using two-dimensional electrophoresis and matrix assisted laser desorption ionization - time of flight mass spectrometry-based protein identification of the spots that displayed Western blotting signals with anti-neutrophil cytoplasmic antibody-positive sera. The prevalence of IgG, IgA and secretory IgA [sIgA] to chitinase 3-like protein 1 [CHI3L1] was analysed by enzyme-linked immunosorbent assays using recombinant CHI3L1 in 110 patients with Crohn's disease [CD], 95 with ulcerative colitis [UC], 126 with coeliac disease [CeD] and 86 healthy controls [HCs]. Results: The 18-glycosylhydrolase family member CHI3L1 was identified as a neutrophil autoantigenic target. CD patients displayed significantly higher levels of IgG to CHI3L1 than patients with UC and CeD (p < 0.0001, respectively). IgA and sIgA to CHI3L1 was significantly higher in CD than in UC, CeD and HCs [p < 0.0001, respectively]. IgA and sIgA to CHI3L1 demonstrated the highest prevalence in CD [25.5%, 28/110; and 41.8%%, 46/110] compared to HCs [2.3%, 2/86; and 4.7%%, 4/86; p = 0.0015 and p < 0.0001] and are associated with a more complicated progression of CD. Conclusion: CHI3L1 is a novel neutrophil autoantigenic target in CD. IgA and sIgA to CHI3L1 may serve as novel markers for CD and may facilitate the serological diagnosis of IBD.

Original languageEnglish
Pages (from-to)894-904
Number of pages11
JournalJournal of Crohn's and Colitis
Volume13
Issue number7
DOIs
Publication statusPublished - Jul 25 2019

Keywords

  • Crohn's disease
  • Inflammatory bowel disease
  • autoantibody
  • chitinase-3 like protein 1
  • enzyme-linked immunosorbent assay

ASJC Scopus subject areas

  • Gastroenterology

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    Deutschmann, C., Sowa, M., Murugaiyan, J., Roesler, U., Röber, N., Conrad, K., Laass, M. W., Bogdanos, D., Sipeki, N., Papp, M., Rödiger, S., Roggenbuck, D., & Schierack, P. (2019). Identification of Chitinase-3-Like Protein 1 as a Novel Neutrophil Antigenic Target in Crohn's Disease. Journal of Crohn's and Colitis, 13(7), 894-904. https://doi.org/10.1093/ecco-jcc/jjz012