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

Abstract

Identify a biomarker in blood obtained at hospital admission that estimates the neurologic morbidity risk for carbon monoxide (CO) poisoning. Observational cohort study and murine model. Retrospective and prospective data from two emergency departments and laboratory investigations. This study compared 114 CO-poisoned patients (57 retrospective, 57 prospective) with 89 samples from age and sex matched controls. None. 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. MBP-MPs are an index for adverse outcome risk in CO-poisoned patients because they initiate an adaptive immune response.