Research Department, Stavanger University Hospital, Norway.
Unit of Gastroenterology, Department of Internal Medicine, Stavanger University Hospital, Norway.
Innate Immun. 2021 May;27(4):286-293. doi: 10.1177/17534259211014252. Epub 2021 May 3.
Fatigue is common in all chronic inflammatory and autoimmune diseases. A conceptual model for understanding the biological basis of fatigue describes it as being a part of the sickness behaviour response generated by pro-inflammatory cytokines and other mediators. We hypothesised that the pro-inflammatory high mobility group box 1 (HMGB1) protein is a fatigue-inducing molecule and that auto-Abs against HMGB1 reduce fatigue. We measured Abs against disulphide (ds) HMGB1 and fully reduced (fr) HMGB1 in plasma from 57 patients with Crohn's disease. Fatigue was rated using the fatigue visual analogue scale (fVAS) and disease activity with faecal calprotectin, C-reactive protein and the Simple Endoscopic Score for Crohn's disease. Multivariable regression models identified anti-dsHMGB1 and anti-frHMGB1 Abs as the strongest contributing factors for fVAS scores ( = -29.10 ( = 0.01), = 0.17, and = -17.77 ( = 0.01), = 0.17, respectively). Results indicate that anti-HMGB1 auto-Abs alleviate fatigue possibly by down-regulating HMGB1-induced sickness behaviour.
疲劳是所有慢性炎症性和自身免疫性疾病的常见症状。一个用于理解疲劳的生物学基础的概念模型将其描述为炎症细胞因子和其他介质产生的疾病行为反应的一部分。我们假设促炎高迁移率族蛋白 B1 (HMGB1) 是一种引起疲劳的分子，而针对 HMGB1 的自身抗体可以减轻疲劳。我们测量了 57 名克罗恩病患者血浆中针对二硫键 (ds) HMGB1 和完全还原 (fr) HMGB1 的抗体。疲劳通过疲劳视觉模拟量表 (fVAS) 进行评估，疾病活动度通过粪便钙卫蛋白、C 反应蛋白和简单克罗恩病内镜评分进行评估。多变量回归模型确定了抗 dsHMGB1 和抗 frHMGB1 抗体是 fVAS 评分的最强影响因素（ = -29.10（ = 0.01）， = 0.17，和 = -17.77（ = 0.01）， = 0.17，分别）。结果表明，针对 HMGB1 的自身抗体减轻疲劳的可能机制是通过下调 HMGB1 诱导的疾病行为。
