Department of Microbiology-Infectious Disease and Immunology, Faculty of Medicine, University Laval, Quebec, Canada; Leishmaniasis Research Laboratory at Natan Portella Tropical Diseases Institute, Teresina, Brazil.
Instituto Oswaldo Cruz - FIOCRUZ, Rio de Janeiro, Brazil.
Cytokine. 2022 Jan;149:155747. doi: 10.1016/j.cyto.2021.155747. Epub 2021 Oct 27.
Visceral leishmaniasis (VL) is caused by the protozoan Leishmania spp, transmitted by sand fly bites. VL is one of the deadliest tropical infection diseases, yet the coinfection with HIV virus drastically increases relapses, treatment failure and mortality. The concomitant action of these two pathogens leads to high cellular activation independently of the progression to AIDS. In addition, microbial translocation and bacterial infections are thought to contribute worsening the clinical picture. Identifying biomarkers associated with disease severity is of interest for clinical management of patients with VL-HIV/AIDS. Thus, we analyzed in the sera several markers including interleukins (IL-1β, IL-6, IL-8, and IL-17), interferon-γ (IFN- γ), tumor necrosis factor (TNF), lipopolysaccharide (LPS), soluble CD14 (sCD14), macrophage migration inhibitory factor (MIF) and intestinal fatty acid-binding protein (IFABP). These markers were compared with disease severity in 24 patients with VL/HIV presenting different clinical outcomes. Disease severity was defined by the probability of death calculated using a score set system derived by the Kala-Cal® software. Probability of death ranged from 3.7% to 97.9%, with median of 28.8%. Five patients died (20%). At the univariate analysis, disease severity was correlated with TNF, IFN-γ and sCD14. LPS was positively correlated with sCD14 specifically in patients with low CD4 count (CD4 T-cell <200 cells/mL). Most importantly, the multivariate analysis including LPS, CD4count and sCD14 showed that sCD14 was the only independent predictor for disease severity and death. Altogether, our results indicated that sCD14 is a powerful marker of pathogenicity and death for patients with VL-HIV/AIDS.
内脏利什曼病（VL）是由原生动物利什曼原虫属引起的，通过沙蝇叮咬传播。VL 是最致命的热带传染病之一，然而与 HIV 病毒的合并感染会大大增加复发、治疗失败和死亡率。这两种病原体的共同作用导致细胞高度激活，而与艾滋病的进展无关。此外，微生物易位和细菌感染被认为会导致临床病情恶化。确定与疾病严重程度相关的生物标志物对于 VL-HIV/AIDS 患者的临床管理具有重要意义。因此，我们分析了 24 例 VL/HIV 患者血清中的几种标志物，包括白细胞介素（IL-1β、IL-6、IL-8 和 IL-17）、干扰素-γ（IFN-γ）、肿瘤坏死因子（TNF）、脂多糖（LPS）、可溶性 CD14（sCD14）、巨噬细胞移动抑制因子（MIF）和肠脂肪酸结合蛋白（IFABP）。这些标志物与具有不同临床结局的 24 例 VL/HIV 患者的疾病严重程度进行了比较。疾病严重程度通过 Kala-Cal®软件衍生的评分系统计算死亡概率来定义。死亡概率从 3.7%到 97.9%不等，中位数为 28.8%。5 名患者死亡（20%）。在单因素分析中，疾病严重程度与 TNF、IFN-γ 和 sCD14 相关。LPS 与 sCD14 呈正相关，特别是在 CD4 计数低（CD4 T 细胞 <200 个/毫升）的患者中。最重要的是，包括 LPS、CD4 计数和 sCD14 的多变量分析表明，sCD14 是疾病严重程度和死亡的唯一独立预测因子。总之，我们的结果表明 sCD14 是 VL-HIV/AIDS 患者致病性和死亡的有力标志物。
