Schotthoefer Anna M, Schrodi Steven J, Meece Jennifer K, Fritsche Thomas R, Shukla Sanjay K
Marshfield Clinic Research Institute, Marshfield Clinic, Marshfield, Wisconsin, United States of America.
Marshfield Labs, Marshfield Clinic, Marshfield, Wisconsin, United States of America.
PLoS One. 2017 Jun 19;12(6):e0179655. doi: 10.1371/journal.pone.0179655. eCollection 2017.
Human anaplasmosis (HA) is an emerging tick-borne disease that may present as a mild flu-like illness or a life threatening, sepsis-like condition. Although disease severity is hypothesized to relate to immunopathology and immune dysfunction in humans, studies to directly measure immune responses in infected humans have been very limited. We quantified cytokines in 80 confirmed HA patients using a multiplex chemiluminescence immunoassay system and compared similarly measured responses in 1000 control subjects. Pro-inflammatory cytokines were significantly elevated in HA patients (all seven p<0.0001). Interferon gamma (IFN-γ) concentrations were particularly high, with average concentrations 7.8 times higher in the HA patients than the controls. A subset of cytokines consisting of IL-1β, IL-8, IL-6, TNF-α, and IL-10 was also coordinately high and significantly associated with severity of thrombocytopenia in HA patients. Patients with infections in the very acute stage (≤ 4 days ill) tended to have the highest IFN-γ, IL-12p70, and IL-2 levels. Higher concentrations of IL-13 and IL-5 were associated with diarrhea and vomiting. Our findings support a pathophysiological role for a pro-inflammatory response in HA, especially with regard to the modulation of hematopoiesis and subsequent hematopoietic complications.
人粒细胞无形体病（HA）是一种新出现的蜱传疾病，可能表现为类似流感的轻症，也可能是危及生命的败血症样病症。尽管据推测疾病严重程度与人类的免疫病理学和免疫功能障碍有关，但直接测量受感染人类免疫反应的研究非常有限。我们使用多重化学发光免疫分析系统对80例确诊的HA患者的细胞因子进行了定量，并比较了1000名对照受试者的类似测量反应。HA患者的促炎细胞因子显著升高（所有七种细胞因子p<0.0001）。干扰素γ（IFN-γ）浓度特别高，HA患者的平均浓度比对照组高7.8倍。由白细胞介素-1β（IL-1β）、白细胞介素-8（IL-8）、白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）和白细胞介素-10（IL-10）组成的一组细胞因子也协同升高，并且与HA患者血小板减少症的严重程度显著相关。处于极急性期（患病≤4天）的感染患者往往具有最高的IFN-γ、白细胞介素-12p70和白细胞介素-2水平。较高浓度的白细胞介素-13（IL-13）和白细胞介素-5（IL-5）与腹泻和呕吐有关。我们的研究结果支持促炎反应在HA中的病理生理作用，特别是在造血调节和随后的造血并发症方面。
