ABSTRACT
Background and Aim: Serum immunoglobulins were reported to be associated with clinical characteristics of inflammatory bowel disease. However, whether a difference exists in the serum immunoglobulins levels in patients with Crohn's disease (CD) with different disease location and behavior phenotypes remains unclear. Therefore, this study aimed to explore the associations of serum immunoglobulins levels with specific CD phenotypes. Methods: Patients with CD having recorded serum immunoglobulins levels were recruited through multicenter collaborative efforts. The associations between serum immunoglobulins levels and distinct phenotypes of CD were evaluated using multiple logistic regression models. Results: A total of 608 patients with CD were included in the study. Elevated (above the upper limit of normal) serum immunoglobulin G (IgG), IgA, IgM, and IgG4 were identified in 24.5, 17.4, 2.1, and 8.2% of patients, respectively. Elevated serum IgG4 levels negatively correlated with complicated disease behavior [odds ratio (OR) 0.49, 95% confidence interval (CI) 0.26-0.92]. Elevated serum IgG was linked to isolated ileal disease with an OR of 0.37 (95% CI 0.23-0.61). The ORs of isolated ileal disease progressively reduced across increasing quartiles of IgG (P for trend < 0.001). The adjusted ORs of isolated ileal disease for increasing quartiles of IgM were 1.82 (1.07-3.1), 1.92 (1.14-3.24), 1.17 (0.69-1.98), and 1 (P for trend = 0.008). Besides, serum IgA and IgG levels significantly correlated with several disease activity indices. Conclusions: These results suggested that certain serum immunoglobulins were associated with specific disease phenotypes of CD. Further investigations to account for the associations are warranted.
ABSTRACT
OBJECTIVES: Transcribed ultraconserved region (T-UCR) uc.261 is reported to participate in intestinal mucosa barrier damage in Crohn's disease (CD). The aim of this study was to determine the association with disease activity and intestinal permeability. METHODS: Uc.261 level in colon mucosa and Harvey-Bradshaw Index (HBI) were evaluated in 20 active CD patients. Uc.261 expression and transepithelial electrical resistance (TEER) were determined in Caco2 and T84 cells treated with tumor necrosis factor alpha (TNF-α), respectively. Body weight, disease activity index (DAI), colon length, histological index (HI), intestinal permeability to FITC-dextran, uc.261, and tight junction proteins (TJPs) levels were evaluated in BALB/C mice treated with saline enema, trinitrobenzene sulfonic acid (TNBS)/ethanol enema, and anti-TNF-α monoclonal antibody injection, respectively. RESULTS: Uc.261 expression was overexpressed in CD patients, TNF-α treated cells, and colitis mice. Uc.261 expression was positively correlated with HBI (r = 0.582, p = 0.007) in CD patients, and positively correlated with TNF-α concentration and negatively correlated TEER in Caco2 and T84 cells (all p < 0.05). Furthermore, uc.261 was positively correlated with DAI (r = 0.824, p = 0.008), HI (r = 0.672, p = 0.021), and intestinal permeability (r = 0.636, p = 0.012), while negatively correlated with body weight (r = -0.574, p = 0.035), colon length (r = -0.866, p = 0.017), and TJP expression (all p < 0.05) in colitis mice. CONCLUSIONS: Uc.261 expression was closely correlated with disease activity and intestinal permeability in CD. Anti-TNF-α treatment may play its role through suppressing uc.261 expression in colitis mice.
ABSTRACT
Ulcerative colitis (UC) is one of the two major forms of inflammatory bowel disease (IBD). Both innate immunity and adaptive immunity are aberrant in IBD. The pathogenesis of UC includes abnormal inflammation and immune responses of the digestive tract. Natural killer T (NKT) cells participate in the innate and adaptive immune responses, together with a vast array of cytokines. Recent studies suggested that IL-13, IL5 and IL-4 are involved in the occurrence and the development of UC. Manipulating NKT cells may be a potential strategy to reconstruct the abnormal immune responses in UC. In this review, we explore the roles of NKT cells and cytokines in UC. Additionally, neutralizing antibodies and inhibitors of cytokines produced by NKT cells or their receptors are also discussed as novel therapeutic choices for UC.
