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 (B = −29.10 (P = 0.01), R² = 0.17, and B = −17.77 (P = 0.01), R² = 0.17, respectively). Results indicate that anti-HMGB1 auto-Abs alleviate fatigue possibly by down-regulating HMGB1-induced sickness behaviour.

疲劳在所有慢性炎症和自身免疫性疾病中都很常见。用于理解疲劳生物学基础的概念模型将其描述为由促炎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组框 1 (HMGB1) 蛋白是一种诱导疲劳的分子，并且针对 HMGB1 的自身抗体可减轻疲劳。我们测量了来自 57 名克罗恩病患者血浆中二硫化物 (ds) HMGB1 和完全减少 (fr) HMGB1 的 Abs。使用疲劳视觉模拟评分 (fVAS) 和粪便钙卫蛋白、C 反应蛋白和克罗恩病的简单内窥镜评分对疲劳进行评估。B  = -29.10 ( P  = 0.01)，R ²  = 0.17，B  = -17.77 ( P  = 0.01)，R ²  = 0.17)。结果表明，抗 HMGB1 自身抗体可能通过下调 HMGB1 诱导的疾病行为来减轻疲劳。