Identification of Chitinase-3-like protein 1 as a novel neutrophil antigenic target in Crohn’s disease.
J Crohns Colitis. 2019 Feb 07;:
Authors: Deutschmann C, Sowa M, Murugaiyan J, Roesler U, Röber N, Conrad K, Laass M, Bogdanos D, Sipeki N, Papp M, Rödiger S, Roggenbuck D, Schierack P
Objective: There is an increasing incidence of inflammatory bowel disease (IBD). Autoimmune responses partake in the pathophysiology of IBD, however, its underlying pathways and target antigens are not yet 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 (MALDI-TOF-MS) based protein identification of the spots that displayed Western blotting signals with anti-neutrophil cytoplasmic antibody (ANCA)-positive sera. The prevalence of IgG, IgA, and secretory IgA (sIgA) to chitinase 3-like protein 1 (CHI3L1) was analyzed by enzyme-linked immunosorbent assays (ELISAs) using recombinant CHI3L1 in 110 patients with Crohn’s disease (CD), 95 with ulcerative colitis (UC), 126 with celiac 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, respetively). 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< 0.0001, respectively) 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.
PMID: 30753386 [PubMed – as supplied by publisher]