The utility of apoptosis inhibitor of macrophages as a possible diagnostic marker in patients with Crohn’s disease

Abstract

BackgroundApoptosis inhibitor of macrophages (AIM) was initially identified as an apoptosis inhibitor that supports the survival of macrophages against various apoptosis-inducing stimuli, and AIM produced by macrophages may contribute to the pathogenesis of inflammatory bowel diseases (IBDs). However, there have been no reports on the kinetics of AIM in IBD and the impact of AIM on the pathogenesis of IBD. In this study, we aimed to investigate the diagnostic utility of levels of AIM and their correlation with the activity of Crohn’s disease (CD) and IBD.MethodsWe used an enzyme-linked immunosorbent assay (ELISA) to examine AIM serum levels in 16 healthy subjects and 90 patients with inflammatory bowel diseases, namely 39 with CD and 51 with ulcerative colitis (UC), as well as 17 patients with Behcet’s disease (BD) as intestinal disease controls. We compared serum AIM levels among groups and examined whether there were correlations between serum AIM levels and disease activity and type. We also performed immunohistochemical staining of AIM in intestinal tissues of patients with CD.ResultsSerum AIM levels were significantly higher in patients with CD than in patients with UC, BD, and controls (3.27 ± 2.14, 1.88 ± 1.43, 2.34 ± 1.37, and 2.13 ± 0.64 μg/ml, respectively; P < 0.01). There was no difference in serum AIM levels before and after treatment in patients with CD. However, in these patients the diagnostic rate using AIM was better than that based on anti-Saccharomyces cerevisiae antibodies. AIM was expressed in macrophages that were positive for CD14, CD16, or both in the intestinal tissues of patients with CD.ConclusionsAIM is a novel biomarker of CD that can distinguish CD from UC or BD. It is suggested that AIM may contribute to intestinal inflammation by inhibiting the apoptosis of macrophages.

Role of apoptosis inhibitor of macrophages in patients with IgG4‑related disease/autoimmune pancreatitis and the clinical characteristics associated with this condition

“…It remains unknown how disease activity indexes or predictors of relapse influence parameters, such as the Crohn's disease Activity Index (CDAI) in Crohn's disease. Furthermore, there is no association between serum AIM concentrations and the CDAI in patients with Crohn's disease (13). However, the results of the present study suggested that serum AIM concentrations may potentially be an indicator of AIP.…”

“…Moreover, it has been demonstrated that AIM may function as a biomarker for distinguishing between different inflammatory bowel diseases. Furthermore, AIM is a novel biomarker of Crohn's disease, which can be used to distinguish Crohn's disease from ulcerative colitis and Behcet's disease (13). According to these aforementioned studies, as IgG4-RD and AIP are diseases that are characterized by tissue inflammation and fibrosis, it can be hypothesized that AIM may function as a diagnostic or active biomarker of autoimmune and inflammatory diseases with tissue fibrosis, such as IgG4-RD and AIP.…”

“…In a previous study, it was demonstrated that there was an association between AIM and hepatic fibrosis in chronic hepatitis C (12). It has also been determined that AIM may function as a biomarker for distinguishing between different inflammatory bowel diseases (13). It can thus be hypothesized that AIM may function as a biomarker for autoimmune and inflammatory diseases with tissue fibrosis, such…”

Approaches for Controlling Antibody-Mediated Allograft Rejection Through Targeting B Cells

“…CD22-mediated signaling also induces immune tolerance via CD22-CD22L interaction and CD22-mediated inhibition of the BCR-mediated signal (227,228) and CD22 (+) mature B cell apoptosis (71). (B) As a scavenger protein, it has been reported that free Apoptosis inhibitor of macrophage (AIM) works to suppress inflammation, tissue injury and tissue regeneration through phagocytic activity during acute kidney injury (233)(234)(235)(236)(237)(238)(239)(240)(241) and AIM mediates immune tolerance induction by IL-10 and suppresses the immune response by inducing macrophages with immunosuppressive phenotype activation (35) and cooperates with TGF-beta to suppress B cell proliferation and antibody production (233). (C) As a polyclonal IgM antibody, IgM-enriched IVig strongly suppresses cell proliferation, has a inhibitory effect in complement activity (257,258), and alleviates the humoral immunity-associated pathological condition in severe infection, organ ischemia, and transplants (42, 253-256, 258, 259).…”

“…Thus, free AIM is involved in the repair of acute kidney injury, because delayed or deficient removal of dead cells, or both, may cause secondary inflammation and fibrosis in tissues and may impair the repair of tissue damage and the regeneration of such tissues (237). Alternatively, macrophages produce AIM (236), which is involved in the pathophysiology of inflammatory colitis through the maintenance of the survival of macrophages, and the elimination of dead cells and toxic substances in hepatitis by supporting the phagocytic activity of macrophages (239)(240)(241). In the field of transplantation, it has been reported that the blood concentration of free AIM increases during acute cellular rejection in cardiac allograft rejection (242).…”