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Institute
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.
Antibodies executing catalytic activity are referred to as antibody enzymes or short “abzymes” and may have diagnostic relevance. Abzymes with deoxyribonuclease (DNase) activity have been demonstrated in patients with autoimmune and infectious diseases. Despite several reports on the occurrence of DNase abzymes in systemic autoimmune rheumatic diseases, conclusive data about DNase activity of antibodies in patients with spondyloarthritides (SpAs) are lacking. In recent cross-sectional studies evaluating levels of IgG DNase activity in patients with psoriatic arthritis (PsA), reactive arthritis (ReA), and ankylosing spondylitis (AS), DNase activity of IgG has been assessed by the rivanol clot method and confirmed by agarose gel electrophoresis. Remarkably, levels of IgG DNase activity were significantly higher in sera of SpA patients than those in control subjects. In patients with PsA, ReA, and AS, a positive correlation of DNase IgG activity with synovitis, disease activity, and stage of spondylitis was observed, respectively. Given the involvement of autoimmune reactions in cytolysis and connective tissue degradation in PsA, ReA, and to a lesser extent in AS, abzymes might have an impact on the pathophysiology of SpAs. Detection of IgG DNase activity in patients suffering from SpA represents an exciting new research field and may assist in the differential diagnosis of SpA.