Ono Yohei, Kanmura Shuji, Morinaga Yuko, Oda Kohei, Kawabata Katsuto, Arima Shiho, Sasaki Fumisato, Nasu Yuichirou, Tanoue Shiroh, Hashimoto Shinichi, Taguchi Hiroki, Uto Hirofumi, Tsubouchi Hirohito, Ido Akio
Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1, Sakuragaoka, Kagoshima, 890-8520, Japan.
Center for Digestive and Liver Diseases, Miyazaki Medical Center Hospital, Miyazaki, Japan.
BMC Gastroenterol. 2017 Mar 11;17(1):40. doi: 10.1186/s12876-017-0591-z.
Apoptosis 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.
We 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.
Serum 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.
AIM 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.
巨噬细胞凋亡抑制因子（AIM）最初被鉴定为一种凋亡抑制因子，可支持巨噬细胞在各种诱导凋亡的刺激下存活，巨噬细胞产生的AIM可能与炎症性肠病（IBD）的发病机制有关。然而，关于IBD中AIM的动力学以及AIM对IBD发病机制的影响尚无报道。在本研究中，我们旨在探讨AIM水平的诊断效用及其与克罗恩病（CD）和IBD活动度的相关性。
我们采用酶联免疫吸附测定（ELISA）检测了16名健康受试者、90例炎症性肠病患者（其中39例为CD，51例为溃疡性结肠炎（UC））以及17例白塞病（BD）患者（作为肠道疾病对照）的血清AIM水平。我们比较了各组之间的血清AIM水平，并检查血清AIM水平与疾病活动度和类型之间是否存在相关性。我们还对CD患者的肠道组织进行了AIM的免疫组织化学染色。
CD患者的血清AIM水平显著高于UC、BD患者及对照组（分别为3.27±2.14、1.88±1.43、2.34±1.37和2.13±0.64μg/ml；P<0.01）。CD患者治疗前后的血清AIM水平无差异。然而，在这些患者中，使用AIM的诊断率优于基于抗酿酒酵母抗体的诊断率。AIM在CD患者肠道组织中CD14、CD16阳性或两者均阳性的巨噬细胞中表达。
AIM是CD的一种新型生物标志物，可将CD与UC或BD区分开来。提示AIM可能通过抑制巨噬细胞凋亡而导致肠道炎症。
