Published online Nov 14, 2023. doi: 10.3748/wjg.v29.i42.5728
Peer-review started: June 28, 2023
First decision: September 1, 2023
Revised: October 3, 2023
Accepted: November 2, 2023
Article in press: November 2, 2023
Published online: November 14, 2023
Chitinase 3-like 1 (CHI3L1) is a 40 kDa heparin-, chitin-, hyaluronan-, and collagen-binding glycoprotein expressed by various cell types, including fibroblast-like cells, macrophages, neutrophils, and colonic epithelial cells (CEC). Under normal conditions, CHI3L1 levels are extremely low; however, under inflammatory conditions, they are also expressed at elevated levels in CEC and macrophages. Upregulated expression of CHI3L1 in the lamina propria and CECs has been described in patients with inflammatory bowel disease (IBD). This upregulation, along with the loss of tolerance to CHI3L1, can enhance the adhesion and invasion of certain commensal and/or pathogenic bacteria via carbohydrate binding (chitin binding protein 21) or homologous motifs (for example, ChiA). Microbial overload, along with mechanical and/or functional derangement of the gut barrier, can lead to the uncontrolled uptake of various luminal bacteria and/or bacterial products. As a result, enhanced bacterial translocation exacerbates local and systemic proinflammatory processes already underway, thereby contributing to disease exacerbation and complications.
Given the current state of knowledge, the precise function and mechanism of CHI3L1 in the development of IBD, loss of tolerance to this antigen, formation of immunoglobulin A (IgA) autoantibodies against it, and their role in the patho
To evaluate the predictive value of different immunoglobulin subtypes of the novel serological marker, anti-CHI3L autoantibodies (aCHI3L1), in terms of their ability to define the disease phenotype, therapeutic strategy, and long-term disease course in a group of adult IBD patients with prospective follow-up.
A total of 257 patients with Crohn’s disease (CD) and 180 patients with ulcerative colitis (UC) from a tertiary IBD referral center in Hungary (Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen) were tested for IgG, IgA, and secretory IgA (sIgA) type aCHI3L1 using enzyme-linked immunosorbent assay with recombinant CHI3L1, along with 86 healthy controls.
Enhanced formation of IgA and sIgA (sub)-type against CHI3L1 was first detected in adult patients with CD, which was associated with the clinical phenotype in a tertiary referral IBD center in Hungary. This observational study presents, for the first time, longitudinal and prospective results on the predictive ability of aCHI3L1 antibodies to identify disease-specific complications and surgical requirements, which are critical for patient care. The presence of IgA or sIgA aCH3L1 antibodies in CD patients with both inflammatory luminal disease and colon involvement at the time of diagnosis indicates a faster progression towards a complicated disease course in time-dependent models.
CHI3L1 is a newly discovered neutrophil autoantigenic target in IBD. By taking into account the classes of antibodies and utilizing location-based predictions, serology in IBD may undergo a significant transformation in the future.
Based on both the pathogenic and clinical heterogeneity of IBD, instead of the “the one size fits all” model, an increasing amount of data points towards the need for the development and application of prognostic matrix models. Therefore, identifying new biomarkers for this purpose is of utmost importance. A significantly higher prevalence of IgA and sIgA (sub)type antibodies against CHI3L1 in patients with colonic involvement, along with a positive predictive value for complicated disease course in only this subgroup of CD patients, could be considered as an indirect confirmation of colonic origin of these antibodies. Further studies to assess the presence of aCHI3L1 antibodies in different parts of the gut mucosa of IBD patients are needed to confirm this hypothesis. Unravelling the role of CHI3L1 and aCHI3L1 autoantibodies in IBD pathogenesis can help identify new potential therapeutic targets for IBD.