Kirby Institute, The University of New South Wales, Sydney (UNSW Sydney), Wallace Wurth Building, High St, Kensington, NSW 2052, Australia.
The University of Sydney, School of Public Health, Faculty of Medicine and Health, Edward Ford Building (A27), Fisher Rd, NSW 2006, Australia; Department of Human Behaviour, School of Psychiatry, UNSW Sydney, Kensington, NSW 2052, Australia.
Brain Behav Immun. 2021 Mar;93:186-193. doi: 10.1016/j.bbi.2021.01.005. Epub 2021 Jan 9.
The acute sickness response (ASR) is a stereotyped set of symptoms including fatigue, pain, and disturbed mood, which are present in most acute infections. The immunological mechanisms of the ASR are conserved, with variations in severity determined partly by the pathogen, but also by polymorphisms in host genes. The ASR was characterised in three different serologically-confirmed acute infections in Caucasians (n = 484) across four symptom domains or endophenotypes (termed 'Fatigue', 'Musculoskeletal pain', 'Mood disturbance', and 'Acute sickness'). Correlations were sought with functional single nucleotide polymorphisms in the NLRP3 inflammasone pathway and severity of the endophenotypes. Individuals with severe Fatigue, Musculoskeletal pain, or Mood endophenotypes were more likely to have prior episodes of significant fatigue (11.4 vs. 3.8%, p = 0.07), pain (14.3 vs. 1.2%, p = 0.001), or Mood disturbance (13 vs 1%, p=0.001), suggesting trait characteristics. The high functioning allele of the rs35829419 SNP in NLRP3 was more common in those with severe Fatigue (OR = 13.3, 95% CI: 1.7-104), particularly in a dominant inheritance pattern (OR = 13.4, 95% CI: 1.8-586.3). In a multivariable analysis assuming dominant inheritance, both rs35829419 and the rs4848306 SNP in Interleukin(IL)-1β, were independently associated with severe Fatigue (OR = 29.6, 95% CI: 2.6-330.9 and OR = 13, 95% CI: 2.7-61.8, respectively). The severity of fatigue in acute infection is influenced by genetic polymorphisms in NLRP3 and IL-1β.
急性病反应（ASR）是一组刻板的症状，包括疲劳、疼痛和情绪紊乱，这些症状在大多数急性感染中都存在。ASR 的免疫机制是保守的，其严重程度的变化部分取决于病原体，但也取决于宿主基因的多态性。在四个症状领域或内表型（称为“疲劳”、“肌肉骨骼疼痛”、“情绪紊乱”和“急性病”）中，在 484 名白种人血清学确诊的三种不同急性感染中对 ASR 进行了描述。在 NLRP3 炎症体途径的功能性单核苷酸多态性与内表型严重程度之间寻求相关性。具有严重疲劳、肌肉骨骼疼痛或情绪内表型的个体更有可能有过严重疲劳（11.4%对 3.8%，p=0.07）、疼痛（14.3%对 1.2%，p=0.001）或情绪紊乱（13 对 1%，p=0.001）的既往发作，表明存在特质特征。NLRP3 中 rs35829419 SNP 的高功能等位基因在严重疲劳患者中更为常见（OR=13.3，95%CI：1.7-104），尤其是在显性遗传模式下（OR=13.4，95%CI：1.8-586.3）。在假设显性遗传的多变量分析中，rs35829419 和白细胞介素（IL）-1β中的 rs4848306 SNP 均与严重疲劳独立相关（OR=29.6，95%CI：2.6-330.9 和 OR=13，95%CI：2.7-61.8）。急性感染中疲劳的严重程度受 NLRP3 和 IL-1β 中遗传多态性的影响。
