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J Crohns Colitis. 2019 Jul 25;13(7):894-904. doi: 10.1093/ecco-jcc/jjz012.

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

Author information

1
Institute of Biotechnology, Faculty Environment and Natural Sciences, Brandenburg University of Technology Cottbus-Senftenberg, Universitätsplatz, Senftenberg, Germany.
2
Medipan/GA Generic Assays GmbH, Ludwig-Erhard-Ring, Dahlewitz, Berlin, Germany.
3
Institute for Animal Hygiene and Environmental Health, Freie Universität Berlin, Centre for Infectious Medicine, Robert-von-Ostertag-Str., Berlin, Germany.
4
Department of Biotechnology, SRM University-AP, Amaravati, India.
5
Institute of Immunology, Medical Faculty Carl Gustav Carus, Technical University Dresden, Fetscherstraße, Dresden, Germany.
6
Children's Hospital, Medical Faculty Carl Gustav Carus, Technical University Dresden, Fetscherstraße, Dresden, Germany.
7
Department of Rheumatology, School of Health Sciences, University of Thessaly, Larissa, Greece.
8
Department of Internal Medicine, Division of Gastroenterology, Faculty of Medicine, University of Debrecen, Nagyerdei krt., Debrecen, Hungary.

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.

KEYWORDS:

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

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