Extensive Investigation of Immune Responses Against Borrelia Burgdorferi to Improve Diagnosis of Lyme Disease in Children: an Observational Study (BRILLIANT Study)
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 502
- 试验地点
- 2
- 主要终点
- Number of Bb-specific ASCs per 10^6 PBMCs
研究概览
简要总结
The investigators propose a single center, prospective observational study in children with Lyme disease (LD), the Borrelia B-cell diagnostics (BRILLIANT) study, to assess the immune response against Borrelia burgdorferi (Bb) with the following main objectives:
- Development of Bb-specific ASC ELISpot as a new test method for diagnosis of early LD.
There is an urgent unmet clinical need for a better diagnostic tool for early LD, as the current standard two-tier testing has low sensitivity in recently infected patients and may show false positive results in recovered patients due to long-term persistence of antibodies against Bb. The measurement of Bb-specific ASC with the ELISpot assay my has the potential to overcome these issues and to improve diagnosis in early LD. 2. Extensive analysis of the immune response in LD. The immune response in LD is not well understood. Large-scale studies assessing the detailed immune cell subsets/phenotypes present in blood, CSF, or synovial fluid of LD patients with respective manifestations are lacking. 3. Isolation and characterization of causative Bb species. Existing literature suggests that Bb genospecies and/or genotypes may determine virulence and manifestations, but large-scale studies assessing Bb genospecies/genotypes in different manifestation of LD are lacking. 4. Collection of clinical data about symptoms, severity, routine laboratory and diagnostic test results, treatment, and outcome of LD. 5. Biobanking samples for analysis in the future.
Project population
Inclusion criteria: Children, 0-17 years of age, at University Children's Hospital Zurich:
- LD differential diagnosis cohort: Patients presenting at the ED with differential diagnosis of LD according to the treating physician.
- Control cohort: Previously healthy patients (HC) with routine blood investigations presenting at the ED or PID outpatient department
Exclusion criteria: Primary or secondary immunodeficiency.
详细描述
Background:
Lyme disease (LD) is the most common tick born disease in Europe. It is caused by an infection with several genospecies of the spirochaetal bacteria Borrelia burgdorferi (Bb).
Although classical disease manifestations are well-known, the clinical presentation in children is often variable and inconclusive, which results in delayed diagnosis and treatment.
Methods/design:
The investigators are conducting an observational cohort study in children with LD. Study site is the University Children's Hospital Zurich. 502 patients will be enrolled. Children from 0-17 years of age presenting with signs and symptoms suspicious for LD are included in the study. Previously healthy children with routine blood investigation are enrolled as healthy controls. Patients will be excluded in cases of primary or secondary immunodeficiency.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 1 Month 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Patients presenting at the ED with differential diagnosis of LD according to the treating physician
排除标准
- •Patients will be excluded in cases of primary or secondary immunodeficiency
研究组 & 干预措施
LD_Diff_Diag
LD differential diagnosis cohort: Patients presenting at the ED with differential diagnosis of LD according to the treating physician
干预措施: venous blood puncture (Procedure)
Heathy_Control
Previously healthy patients (HC) with routine blood investigations presenting at the ED or PID outpatient department
干预措施: venous blood puncture (Procedure)
结局指标
主要结局
Number of Bb-specific ASCs per 10^6 PBMCs
时间窗: 10/2023 - 10/2026
Method: Quantification of Bb-specific ASCs (IgM, IgG, IgA) per 10\^6 PBMCs using ELISpot assay Time: 0 d (hospital admission), (1-14 d), 28 d, 3 m, and 6 m (after hospital admission)
次要结局
- Measurement of percentage and median fluorescence intensity (MFI) of immune cell subsets in blood, CSF and SF(10/2023 - 10/2028)
- Number of Bb-specific T cells per 10^6 PBMCs(10/2023 - 10/2028)
- Concentration of serum antibody levels (IU/mL)(10/2023 - 10/2028)
- Concentration of plasma and CSF cytokine/chemokine levels (pg/mL)(10/2023 - 10/2028)
- Portion of Bb positive LD patients by culture/PCR, identification of Bb species in LD patients(10/2023 - 10/2028)