Institute of Biotechnology, Faculty Environment and Natural Sciences, Brandenburg University of Technology Cottbus-Senftenberg, Universitätsplatz, Senftenberg, Germany.
Medipan/GA Generic Assays GmbH, Ludwig-Erhard-Ring, Dahlewitz, Berlin, Germany.
J Crohns Colitis. 2019 Jul 25;13(7):894-904. doi: 10.1093/ecco-jcc/jjz012.
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.
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].
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.
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.
炎症性肠病[IBD]的发病率不断上升。自身免疫反应参与了 IBD 的病理生理学，但它们的潜在途径和靶抗原尚未完全阐明。
使用二维电泳和基质辅助激光解吸电离-飞行时间质谱法分离从中性粒细胞中分离的全细胞蛋白后，鉴定 IBD 中的自身抗原靶标，并用抗中性粒细胞细胞质抗体阳性血清对显示 Western 印迹信号的斑点进行基于蛋白质鉴定。采用酶联免疫吸附试验，用重组 CHI3L1 分析 110 例克罗恩病[CD]患者、95 例溃疡性结肠炎[UC]患者、126 例乳糜泻[CeD]患者和 86 例健康对照者[HCs]对几丁质酶 3 样蛋白 1[CHI3L1]的 IgG、IgA 和分泌型 IgA[sIgA]的流行率。
18 糖基水解酶家族成员 CHI3L1 被鉴定为中性粒细胞自身抗原靶标。CD 患者对 CHI3L1 的 IgG 水平明显高于 UC 和 CeD 患者（分别为 p<0.0001）。CD 患者的 IgA 和 sIgA 对 CHI3L1 的水平明显高于 UC、CeD 和 HCs[分别为 p<0.0001]。与 HCs[分别为 2.3%，2/86；4.7%，4/86；p=0.0015 和 p<0.0001]相比，CD 患者的 IgA 和 sIgA 对 CHI3L1 的流行率最高[25.5%，28/110；41.8%，46/110]，并且与 CD 更复杂的进展相关。
CHI3L1 是 CD 中的一种新型中性粒细胞自身抗原靶标。IgA 和 sIgA 对 CHI3L1 可能作为 CD 的新型标志物，并有助于 IBD 的血清学诊断。
