Blood Biomarkers for Prognostic Stratification in Guillain-Barré Syndrome
Integration of a Blood Biomarker Panel for Prognostic Stratification in Guillain-Barré Syndrome: A Mexico-Spain Collaborative Study (BioGBS)
Guillain-Barré syndrome (GBS) is an acute immune-mediated peripheral neuropathy characterized by substantial variability in clinical severity, functional recovery, and pain outcomes. The lack of validated and accessible prognostic biomarkers limits early risk stratification and individualized rehabilitation strategies.
This observational, longitudinal, retrospective and prospective study aims to evaluate a panel of five blood biomarkers (EGR1, EGR2, GBP1, miR-29c, and Piccolo) and determine their association with functional recovery, pain trajectories, and neurophysiological characteristics in patients with GBS.
The study will include at least 70 patients with GBS and 70 healthy controls. Patients will undergo longitudinal clinical and molecular assessments across different disease stages, whereas healthy controls will provide a single blood sample for reference measurements. Gene and microRNA expression will be quantified using quantitative reverse transcription polymerase chain reaction (qRT-PCR), and serum Piccolo concentrations will be assessed using ELISA or validated immunoassays.
Clinical assessments will include the GBS Disability Scale, Medical Research Council (MRC) Sum Score, Functional Independence Measure (FIM), and validated pain questionnaires. Molecular and clinical data will be integrated using multivariable statistical analyses to identify prognostic molecular signatures and develop predictive models.
The project also aims to support external validation in Mexican populations through international collaboration with Spanish research institutions.
研究概览
地位
条件
详细说明
Guillain-Barré syndrome (GBS) is an acute immune-mediated polyradiculoneuropathy affecting the peripheral nervous system. It is characterized by heterogeneous clinical presentations, including progressive weakness, sensory disturbances, pain, autonomic dysfunction, and, in severe cases, respiratory failure. Although immunomodulatory treatments and multidisciplinary rehabilitation have improved clinical outcomes, predicting individual recovery trajectories remains challenging.
Current prognostic assessment relies primarily on clinical and electrophysiological parameters, which may not adequately capture the molecular mechanisms underlying immune activation, peripheral nerve injury, remyelination, and functional recovery.
Previous investigations conducted by the research group identified differential expression of EGR1, EGR2, GBP1, and miR-29c in peripheral blood mononuclear cells (PBMCs) obtained from patients with GBS. Differential serum concentrations of the presynaptic protein Piccolo were also identified, suggesting their potential relevance as molecular indicators of disease progression and recovery.
The BioGBS study aims to validate these five candidate biomarkers through longitudinal analysis and integration with clinical, functional, pain-related, and neurophysiological data.
The study will employ an observational, retrospective and prospective longitudinal design, including at least 70 patients diagnosed with GBS and 70 healthy controls. Patients will be assessed at four clinically defined stages: initial diagnosis before immunomodulatory treatment (T0), maximum clinical severity or nadir (T1), onset of sustained functional recovery (T2), and advanced recovery or discharge from rehabilitation (T3). Healthy controls will undergo a single baseline molecular assessment.
Gene expression levels of EGR1, EGR2, GBP1, and miR-29c will be quantified in PBMCs using qRT-PCR. Serum Piccolo concentrations will be determined using ELISA or validated immunoassays.
Functional outcomes will be assessed using the GBS Disability Scale, MRC Sum Score, and FIM. Pain severity and interference will be evaluated using the Brief Pain Inventory-Short Form (BPI-SF), while neuropathic pain will be assessed using the Neuropathic Pain Symptom Inventory (NPSI). Electrophysiological findings will be incorporated when available.
Statistical analyses will include longitudinal mixed-effects models, multivariable regression, principal component analysis, unsupervised clustering, and receiver operating characteristic curve analysis. Predictive models will be developed to identify molecular signatures associated with favorable or unfavorable functional recovery and persistent pain. Internal cross-validation and correction for multiple comparisons will be performed when appropriate.
The study will integrate the existing Spanish TOSGB biological collection and collaborative research activities in Mexico. External validation in Mexican patients is planned to evaluate the transferability of the prognostic biomarkers across different populations and healthcare settings.
No experimental treatment will be assigned. All participants with GBS will receive standard medical care and rehabilitation according to routine clinical practice.
研究类型
注册 (估计的)
联系人和位置
学习联系方式
- 姓名：Antonio Ibarra, PhD
- 电话号码：52 5554197603
- 邮箱：jose.ibarra@anahuac.mx
学习地点
-
-
-
Mexico City、墨西哥
- 招聘中
- Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez
-
接触：
- Antonio Ibarra, PhD
- 电话号码：52 5554197603
- 邮箱：jose.ibarra@anahuac.mx
-
-
-
-
-
Toledo、西班牙
- 招聘中
- Hospital Nacional de Parapléjicos
-
接触：
- Ernesto Doncel Perez, PhD
- 电话号码：52 55 54197603
- 邮箱：ernestod@sescam.jccm.es
-
-
参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
取样方法
研究人群
The study population will consist of patients aged 16 years or older with clinically and neurophysiologically confirmed Guillain-Barré syndrome, recruited from participating hospitals in Spain and Mexico. A comparison group of healthy volunteers aged 18 years or older, with a comparable age and sex distribution, will be included to establish reference biomarker measurements. Patients will undergo longitudinal follow-up, whereas healthy controls will undergo a single baseline assessment.
描述
Inclusion Criteria:
- Diagnosis of Guillain-Barré syndrome based on clinical and neurophysiological criteria.
- Age 16 years or older.
- Availability of biological samples for molecular analysis.
- Written informed consent.
- Availability of longitudinal clinical data.
Exclusion Criteria:
- Alternative diagnosis explaining the neurological manifestations.
- Concomitant active autoimmune disease.
- Severe systemic infection.
- Previous unrelated immunosuppressive treatment.
- Incomplete clinical data or absence of informed consent.
学习计划
研究是如何设计的？
设计细节
- 观测模型：COHORT
- 时间观点：OTHER
队列和干预
团体/队列 |
干预/治疗 |
|---|---|
|
Patients With Guillain-Barré Syndrome
Patients with clinically and neurophysiologically confirmed GBS undergoing longitudinal molecular, functional, pain-related, and neurophysiological assessments across different stages of the disease. |
Peripheral blood samples will be collected from patients with Guillain-Barré syndrome and healthy controls to evaluate a panel of molecular biomarkers. Expression levels of EGR1, EGR2, GBP1, and miR-29c will be quantified in peripheral blood mononuclear cells using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Serum Piccolo concentrations will be measured using ELISA or validated immunoassays. Patients with Guillain-Barré syndrome will undergo longitudinal assessments at predefined clinical stages, whereas healthy controls will undergo a single baseline assessment. No experimental treatment will be administered, and routine clinical management will remain unchanged. |
|
Healthy Controls
Healthy individuals without neurological or autoimmune disorders, selected to provide reference measurements for the candidate blood biomarkers. Controls will undergo a single baseline blood sample collection. |
Peripheral blood samples will be collected from patients with Guillain-Barré syndrome and healthy controls to evaluate a panel of molecular biomarkers. Expression levels of EGR1, EGR2, GBP1, and miR-29c will be quantified in peripheral blood mononuclear cells using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Serum Piccolo concentrations will be measured using ELISA or validated immunoassays. Patients with Guillain-Barré syndrome will undergo longitudinal assessments at predefined clinical stages, whereas healthy controls will undergo a single baseline assessment. No experimental treatment will be administered, and routine clinical management will remain unchanged. |
研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Change in Guillain-Barré Syndrome Disability Score
大体时间：Baseline (Day 1), up to 6 months, and up to 12 months after baseline
|
Change in functional disability measured using the GBS Disability Scale, ranging from 0 (normal health) to 6 (death). Higher scores indicate greater disability. Longitudinal changes will be assessed in relation to blood biomarker expression. 0 (Baseline): Day 1, before initiation of immunotherapy. T1 (Nadir or prolonged plateau): Up to 6 months after baseline. T2 (Onset of clinical recovery): Up to 12 months after baseline. T3 (Advanced recovery or neurorehabilitation discharge): Up to 12 months after baseline. All assessment intervals are calculated from T0 (baseline). Clinical stages are determined according to the patient's disease progression and recovery status. |
Baseline (Day 1), up to 6 months, and up to 12 months after baseline
|
|
Change in Muscle Strength Assessed by the MRC Sum Score
大体时间：Baseline (Day 1), up to 6 months, and up to 12 months after baseline.
|
Change in muscle strength assessed using the Medical Research Council Sum Score, ranging from 0 to 60. Higher scores indicate better muscle strength. Longitudinal changes will be evaluated in association with molecular biomarker profiles. T0 (Baseline): Day 1, before initiation of immunotherapy. T1 (Nadir or prolonged plateau): Up to 6 months after baseline. T2 (Onset of clinical recovery): Up to 12 months after baseline. T3 (Advanced recovery or neurorehabilitation discharge): Up to 12 months after baseline. |
Baseline (Day 1), up to 6 months, and up to 12 months after baseline.
|
次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Change in Functional Independence Measure Score
大体时间：Baseline (Day 1), up to 6 months, and up to 12 months after baseline.
|
Functional independence measured using the Functional Independence Measure (FIM), ranging from 18 to 126. Higher scores indicate greater independence in activities of daily living. T0 (Baseline): Day 1, before initiation of immunotherapy. T1 (Nadir or prolonged plateau): Up to 6 months after baseline. T2 (Onset of clinical recovery): Up to 12 months after baseline. T3 (Advanced recovery or neurorehabilitation discharge): Up to 12 months after baseline. |
Baseline (Day 1), up to 6 months, and up to 12 months after baseline.
|
|
Change in Pain Intensity Assessed by the Brief Pain Inventory
大体时间：Baseline (Day 1), up to 6 months, and up to 12 months after baseline.
|
Change in pain intensity measured using the Brief Pain Inventory-Short Form (BPI-SF), on a scale from 0 to 10, with higher scores indicating greater pain intensity. T0 (Baseline): Day 1, before initiation of immunotherapy. T1 (Nadir or prolonged plateau): Up to 6 months after baseline. T2 (Onset of clinical recovery): Up to 12 months after baseline. T3 (Advanced recovery or neurorehabilitation discharge): Up to 12 months after baseline. |
Baseline (Day 1), up to 6 months, and up to 12 months after baseline.
|
|
Change in Pain Interference Assessed by the Brief Pain Inventory
大体时间：Baseline (Day 1), up to 6 months, and up to 12 months after baseline.
|
Change in the interference of pain with daily activities, measured using the BPI-SF on a scale from 0 to 10, with higher scores indicating greater interference. T0 (Baseline): Day 1, before initiation of immunotherapy. T1 (Nadir or prolonged plateau): Up to 6 months after baseline. T2 (Onset of clinical recovery): Up to 12 months after baseline. T3 (Advanced recovery or neurorehabilitation discharge): Up to 12 months after baseline. |
Baseline (Day 1), up to 6 months, and up to 12 months after baseline.
|
|
Change in Neuropathic Pain Symptom Inventory Score
大体时间：Baseline (Day 1), up to 6 months, and up to 12 months after baseline.
|
Change in neuropathic pain symptoms assessed using the Neuropathic Pain Symptom Inventory (NPSI), with a total score ranging from 0 to 100. Higher scores indicate greater neuropathic pain severity. T0 (Baseline): Day 1, before initiation of immunotherapy. T1 (Nadir or prolonged plateau): Up to 6 months after baseline. T2 (Onset of clinical recovery): Up to 12 months after baseline. T3 (Advanced recovery or neurorehabilitation discharge): Up to 12 months after baseline. |
Baseline (Day 1), up to 6 months, and up to 12 months after baseline.
|
|
Longitudinal Change in EGR1, EGR2, GBP1, and miR-29c Expression
大体时间：Baseline (Day 1), up to 6 months, and up to 12 months after baseline.
|
Relative expression of EGR1, EGR2, GBP1, and miR-29c in PBMCs measured using qRT-PCR and expressed as 2^-ΔCt or 2^-ΔΔCt. Associations with clinical recovery trajectories will be analyzed. T0 (Baseline): Day 1, before initiation of immunotherapy. T1 (Nadir or prolonged plateau): Up to 6 months after baseline. T2 (Onset of clinical recovery): Up to 12 months after baseline. T3 (Advanced recovery or neurorehabilitation discharge): Up to 12 months after baseline. |
Baseline (Day 1), up to 6 months, and up to 12 months after baseline.
|
|
Longitudinal Change in Serum Piccolo Concentration
大体时间：Baseline (Day 1), up to 6 months, and up to 12 months after baseline.
|
Serum Piccolo concentration quantified using ELISA or a validated immunoassay and expressed in pg/mL or ng/mL, depending on assay specifications. T0 (Baseline): Day 1, before initiation of immunotherapy. T1 (Nadir or prolonged plateau): Up to 6 months after baseline. T2 (Onset of clinical recovery): Up to 12 months after baseline. T3 (Advanced recovery or neurorehabilitation discharge): Up to 12 months after baseline. |
Baseline (Day 1), up to 6 months, and up to 12 months after baseline.
|
|
Prognostic Performance of the Combined Blood Biomarker Panel
大体时间：Baseline (Day 1), up to 6 months, and up to 12 months after baseline.
|
Discriminative performance of a combined panel comprising EGR1, EGR2, GBP1, miR-29c, and Piccolo for identifying unfavorable functional recovery, evaluated using the area under the receiver operating characteristic curve (AUC). T0 (Baseline): Day 1, before initiation of immunotherapy. T1 (Nadir or prolonged plateau): Up to 6 months after baseline. T2 (Onset of clinical recovery): Up to 12 months after baseline. T3 (Advanced recovery or neurorehabilitation discharge): Up to 12 months after baseline. |
Baseline (Day 1), up to 6 months, and up to 12 months after baseline.
|
|
Requirement for Mechanical Ventilation
大体时间：From baseline (Day 1) through 12 months after baseline.
|
Proportion of patients requiring invasive mechanical ventilation during the acute phase of GBS and duration of ventilatory support when applicable. |
From baseline (Day 1) through 12 months after baseline.
|
合作者和调查者
研究记录日期
研究主要日期
学习开始 (估计的)
初级完成 (估计的)
研究完成 (估计的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (实际的)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.