Myelin Basic Protein Expressing Microparticles Predict Neurologic Morbidity Risk From Acute Carbon Monoxide Poisoning

OBJECTIVE: Identify a biomarker in blood obtained at hospital admission that estimates the neurologic morbidity risk for carbon monoxide (CO) poisoning. DESIGN: Observational cohort study and murine model. SETTING: Retrospective and prospective data from two emergency departments and laboratory investigations. PATIENTS: This study compared 114 CO-poisoned patients (57 retrospective, 57 prospective) with 89 samples from age and sex matched controls. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We hypothesized that microparticles (MPs) bearing myelin basic protein (MBP) in blood at hospital presentation predicted neurologic sequelae (NS) risk. MBP-MPs/μL in 89 controls subjects was 19 + 12 (sd), the value was 88 + 43 (n = 77, p < 0.001 vs. control) in CO patients who recovered by 1 month based on Global Deterioration Scale (GDS) score = 1, and 146 + 62 (p < 0.001 vs. control and CO-recovered groups) in 37 CO patients with NS at 1 month (GDS > 1). In a murine CO-poisoning model, the risk from brain-derived MBP-MPs was due to sensitizing peripheral lymphocytes. This event, concurrent with neutrophil-mediated blood-brain barrier disruption, triggered neuroinflammation. This also occurred in naive mice injected with MBP-MPs isolated from CO-exposed mice, but not MBP-MPs from controls. Mice rendered immunologically tolerant to MBP, those with ligated cervical lymphatics to block MBP-MPs release to the circulation, neutropenic mice and those treated with human recombinant plasma gelsolin to lyse inflammatory MPs did not exhibit neuroinflammation. CONCLUSIONS: MBP-MPs are an index for adverse outcome risk in CO-poisoned patients because they initiate an adaptive immune response.