Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany.
Department of Physics, Humboldt-Universität zu Berlin, Berlin, Germany.
PLoS Negl Trop Dis. 2021 Mar 23;15(3):e0008906. doi: 10.1371/journal.pntd.0008906. eCollection 2021 Mar.
Chagas' disease (CD), caused by the hemoflagellate protozoan, Trypanosoma cruzi, is endemic in most countries of Latin America. Heart failure (HF) is often a late manifestation of chronic CD, and is associated with high morbidity and mortality. Inflammatory processes mediated by cytokines play a key role in the pathogenesis and progression of CD. Keeping in view the inflammatory nature of CD, this study investigated the possible role of 21 different inflammatory cytokines as biomarkers for prediction and prognosis of CD. The plasma concentration of these cytokines was measured in a group of patients with CD (n = 94), and then compared with those measured in patients with dilated cardiomyopathy (DCM) from idiopathic causes (n = 48), and with control subjects (n = 25). Monovariately, plasma levels of cytokines such as stem cell growth factor beta (SCGF beta), hepatocyte growth factor (HGF), monokine induced by interferon gamma (CXCL9), and macrophage inhibitory factor (MIF) were significantly increased in CD patients with advanced HF compared to control group. None of the cytokines could demonstrate any prognostic potency in CD patients, and only MIF and stromal derived factor-1 alpha (CXCL12) showed significance in predicting mortality and necessity for heart transplant in DCM patients. However, multivariate analysis prognosticated a large proportion of CD and DCM patients. In CD patients, HGF and Interleukin-12p40 (IL-12p40) together separated 81.9% of 3-year survivors from the deceased, while in DCM patients, CXCL12, stem cell factor (SCF), and CXCL9 together discriminated 77.1% of survivors from the deceased. The significant increase in plasma concentrations of cytokines such as HGF and CXCL9 in CD patients, and the ability of these cytokines to prognosticate a large proportion of CD and DCM patients multivariately, encourages further studies to clarify the diagnostic and prognostic potential of cytokines in such patients.
恰加斯病(CD)是由血鞭毛原生动物克氏锥虫引起的,在拉丁美洲的大多数国家都有流行。心力衰竭(HF)是慢性 CD 的晚期表现,与高发病率和死亡率相关。细胞因子介导的炎症过程在 CD 的发病机制和进展中起关键作用。鉴于 CD 的炎症性质,本研究探讨了 21 种不同炎症细胞因子作为 CD 预测和预后生物标志物的可能作用。在一组 CD 患者(n=94)中测量了这些细胞因子的血浆浓度,然后将其与特发性扩张型心肌病(DCM)患者(n=48)和对照组(n=25)测量的浓度进行比较。在单变量分析中,与对照组相比,晚期 HF 的 CD 患者的细胞因子(如干细胞生长因子β(SCGFβ)、肝细胞生长因子(HGF)、干扰素γ诱导的单核细胞因子(CXCL9)和巨噬细胞抑制因子(MIF))的血浆水平显著升高。在 CD 患者中,没有一种细胞因子能够显示出任何预后能力,只有 MIF 和基质衍生因子-1α(CXCL12)在预测 DCM 患者的死亡率和心脏移植的必要性方面具有意义。然而,多变量分析预测了大量 CD 和 DCM 患者。在 CD 患者中,HGF 和白细胞介素-12p40(IL-12p40)一起将 81.9%的 3 年幸存者与死亡者分开,而在 DCM 患者中,CXCL12、干细胞因子(SCF)和 CXCL9 一起将 77.1%的幸存者与死亡者分开。在 CD 患者中,HGF 和 CXCL9 等细胞因子的血浆浓度显著增加,并且这些细胞因子能够多变量预测大量 CD 和 DCM 患者,这鼓励进一步研究以阐明这些患者中细胞因子的诊断和预后潜力。