苏丹内脏利什曼病治愈后患者的细胞免疫反应差异及其对结局的可能影响。

Differences in the Cellular Immune Response during and after Treatment of Sudanese Patients with Post-kala-azar Dermal Leishmaniasis, and Possible Implications for Outcome.

机构信息

WHO Collaborating Centre for Leishmaniasis, Spanish National Center for Microbiology, Instituto de Salud Carlos III (ISCIII), Majadahonda (Madrid), Spain.

CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, Madrid, Spain.

出版信息

J Epidemiol Glob Health. 2024 Sep;14(3):1167-1179. doi: 10.1007/s44197-024-00270-0. Epub 2024 Jul 15.

BACKGROUND

The host cellular immune response associated with two treatments for post-kala-azar dermal leishmaniasis (PKDL) - paromomycin plus miltefosine (Arm 1), and liposomal amphotericin B plus miltefosine (Arm 2) - was examined in Sudanese patients before treatment (D0), at the end of treatment (D42), and during the post-treatment period (D180).

METHODS

Whole blood samples were stimulated with soluble Leishmania antigen for 24 h (whole blood assay [WBA]) and the concentrations of Th1/Th2/Th17-associated cytokines, IP-10, PDL-1 and granzyme B were determined.

RESULTS

The Arm 1 treatment (98.2% cure rate) induced a Th1/Th2/Th17 response, while the Arm 2 treatment (80% cure rate) induced a Th1/Th2 response. Five Arm 2 patients relapsed and showed lower IFN-γ, TNF and IL-1β concentrations at D0 than non-relapsers in this Arm. In patients with low-IFN-γ-production at D0, Arm 1 treatment led to a better host immune response and clinical outcome than Arm 2 treatment.

CONCLUSIONS

A Th1/Th2/Th17 response was associated with a higher cure rate. Patients with low IFN-γ, TNF and IL-1β before treatment are more likely to relapse if they undergo Arm 2-type treatment. Determining IFN-γ, TNF and IL-10 levels prior to treatment could help predict patients at higher risk of relapse/recovery from PKDL.

TRIAL REGISTRATION

ClinicalTrials.gov NCT03399955, Registered 17 January 2018, https://clinicaltrials.gov/study/ NCT03399955.

背景

本研究旨在评估两种治疗方案（阿莫地喹联合米替福新[方案 1]和脂质体两性霉素 B 联合米替福新[方案 2]）治疗黑热病后皮肤利什曼病（PKDL）的苏丹患者的固有免疫应答。在治疗前（D0）、治疗结束时（D42）和治疗后期间（D180），对患者进行全血刺激 24 小时（全血测定[WBA]），检测 Th1/Th2/Th17 相关细胞因子、IP-10、PDL-1 和颗粒酶 B 的浓度。

方法

用可溶性利什曼原虫抗原刺激全血 24 小时（全血测定[WBA]），并测定 Th1/Th2/Th17 相关细胞因子、IP-10、PDL-1 和颗粒酶 B 的浓度。

结果

方案 1 治疗（治愈率 98.2%）诱导 Th1/Th2/Th17 反应，而方案 2 治疗（治愈率 80%）诱导 Th1/Th2 反应。5 例方案 2 患者复发，与方案 2 中的非复发者相比，其在方案 2 治疗时的 IFN-γ、TNF 和 IL-1β浓度较低。在治疗前 IFN-γ 低产生的患者中，方案 1 治疗导致更好的宿主免疫反应和临床结局，优于方案 2 治疗。