Laboratório Interdisciplinar de Pesquisas Médicas, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Rio de Janeiro, Brazil.
Hospital Eduardo de Menezes, Fundação Hospitalar do Estado de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
BMC Infect Dis. 2021 Apr 20;21(1):369. doi: 10.1186/s12879-021-06051-5.
Visceral leishmaniasis (VL) is severe and potentially fatal. Brazil is one of the countries with the greatest endemicity for the disease in the world. The reduction of CD4 T lymphocytes, B cells activation and high levels of inflammatory cytokines (IL-6/IL-8/TNF/IL-1β), plasma LPS, soluble CD14, anti-Leishmania IgG3 and low leptin levels are involved in the immunopathogenesis of VL, most associated with severe VL. Despite relapses occurring in about 4-5% of patients with VL not associated with HIV infection, the factors underlying relapses are little known. Our aim was to identify clinical, laboratory and immunological parameters that may be associated with recurrences in VL.
Fifteen VL patients recruited from Hospital Eduardo de Menezes (BH-MG) were grouped into relapsing (R-VL, n = 5) and non-relapsing (NR-VL, n = 10) and evaluated during active disease, immediately after treatment (post-treatment) and 6 months post-treatment (6mpt). Clinical and laboratory data obtained from medical records were correlated with CD4 and CD8 T cell counts and anti-Leishmania Igs and IL-6 plasma levels and compared to those parameters of ten healthy controls.
During the active phase of VL, despite similarity in the clinical symptoms, the rates of thrombocytopenia, elevated transaminases (AST and ALT) and hyperbilirubinemia were higher in the NR-VL group compared to R-VL (p < 0.05), a profile reversed during the post-treatment phase. All patients had low CD4 T counts in active phase, however, NR-VL patients had a higher gain of this cell type than R-VL in the post-treatment (p < 0.05). There was a significant reduction in IgG3 levels during the follow-up in the NR-VL group compared to the R-VL, especially at 6mpt (p < 0.05). In addition, IgG3 levels were negatively correlated with CD4 T counts in the R-VL group (r = - 0.52). Elevated levels of IL-6 were observed in active VL and correlated with clinical markers of severity.
During active phase of VL, the NR-VL patients presented more severe laboratorial abnormalities compared to R-VL, probably because the latter had already received previous treatment. On the other hand, R-VL exhibited greater impairment of immune reconstitution and a high degree of B lymphocyte activation, which must be a factor that favored relapses.
内脏利什曼病（VL）严重且具有潜在致命性。巴西是世界上疾病流行程度最高的国家之一。CD4 T 淋巴细胞减少、B 细胞激活和高水平的炎症细胞因子（IL-6/IL-8/TNF/IL-1β）、血浆 LPS、可溶性 CD14、抗利什曼原虫 IgG3 和瘦素水平降低与 VL 的免疫发病机制有关，与严重 VL 关系最密切。尽管约 4-5%未感染 HIV 的 VL 患者会出现复发，但导致复发的因素知之甚少。我们的目的是确定可能与 VL 复发相关的临床、实验室和免疫学参数。
从爱德华多·德·梅内塞斯医院（BH-MG）招募了 15 名 VL 患者，分为复发组（R-VL，n=5）和非复发组（NR-VL，n=10），并在疾病活动期、治疗后即刻（治疗后）和治疗后 6 个月（6mpt）进行评估。从病历中获得的临床和实验室数据与 CD4 和 CD8 T 细胞计数以及抗利什曼原虫 Ig 和 IL-6 血浆水平相关，并与 10 名健康对照者的参数进行比较。
在 VL 的活动期，尽管临床症状相似，但 NR-VL 组的血小板减少、转氨酶（AST 和 ALT）升高和高胆红素血症的发生率高于 R-VL（p<0.05），在治疗后阶段这种情况发生逆转。所有患者在活动期均存在 CD4 T 计数降低，但 NR-VL 患者在治疗后 CD4 T 计数增加高于 R-VL（p<0.05）。NR-VL 组在随访期间 IgG3 水平显著下降，尤其是在 6mpt（p<0.05）。此外，R-VL 组 IgG3 水平与 CD4 T 计数呈负相关（r=-0.52）。在活动性 VL 中观察到 IL-6 水平升高，并与严重程度的临床标志物相关。
在 VL 的活动期，NR-VL 患者与 R-VL 相比表现出更严重的实验室异常，这可能是因为后者已经接受了之前的治疗。另一方面，R-VL 表现出更大的免疫重建受损和高度的 B 淋巴细胞激活，这必须是导致复发的一个因素。
