Abstract
ObjectiveTo discover the levels of NLR family pyrin domain-containing 3 (NLRP3) in the cerebrospinal fluid (CSF) from adult patients with community-acquired bacterial meningitis (CABM).MethodsWe enrolled 34 patients with CABM, 20 patients with viral meningitis (VM), and 25 patients with non-inflammatory neurological disease. Data on standard clinical parameters, scores, and outcomes were obtained from clinical records, and inflammasome levels in the CSF were measured by an enzyme-linked immunosorbent assay. The area under the receiver operating characteristic curve (AUROC) was used to quantify the diagnostic and prognostic performance of CSF NLRP3 as a biomarker of CABM.ResultsThe levels of NLRP3 were elevated in the CSF of patients with CABM, but levels for ASC, caspase-1, or other inflammasomes did not vary significantly. CSF NLRP3 was positively correlated with clinical severity and with the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte count, albumin quotient (Qalb), and immunoglobulin G quotient (QIgG). Patients with unfavorable outcomes had higher levels of NLRP3 in the CSF, which were correlated with several blood indicators, including NLR, PLR, and lymphocyte and monocyte counts.ConclusionsOur results suggested that the level of CSF NLRP3 could represent the severity of CABM in adults. CSF NLRP3 may be a good biomarker for the diagnosis of CABM and for the discrimination between CABM and VM. It may also be a better biomarker for predicting the prognosis of adult patients with CABM when compared to the NLR or the lymphocyte and monocyte counts.
Highlights
Community-acquired bacterial meningitis (CABM) is a rare disease affecting all age groups, with an annual incidence of approximately three cases per 100,000 adults in developed countries (Bijlsma et al, 2016)
The CABM group exhibited a significant increase in the neutrophil count, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and levels of C-reactive protein (CRP) and procalcitonin (PCT), while at the same time exhibiting a significant decrease in the lymphocyte count and the lymphocyte-to-monocyte ratio (LMR) when compared with the other two groups (Table 1)
cerebrospinal fluid (CSF) NLRP3 showed good area under the curve (AUC) values for the CABM group in the receiver operating characteristic (ROC) curve analysis (CABM vs. non-CABM: AUC = 0.8784, 95% CI: 0.7932–0.9636, p < 0.0001; CABM vs. viral meningitis (VM): AUC = 0.8279, 95% CI: 0.7182–0.9377, p < 0.0001, Figures 2A, B), suggesting that CSF NLRP3 may be a good diagnostic biomarker for distinguishing between CABM and VM
Summary
Community-acquired bacterial meningitis (CABM) is a rare disease affecting all age groups, with an annual incidence of approximately three cases per 100,000 adults in developed countries (Bijlsma et al, 2016). The poor prognosis and neurological sequelae of severe bacterial meningitis are caused both by the infection itself and by the inflammatory response from the host (Tubiana et al, 2020). The latter involves activation of both cellular and non-cellular components of the immune system, including production of pro-inflammatory cytokines, complement-mediated leukocyte recruitment, and microglial activation (Koelman et al, 2019; Loughran et al, 2019). The levels of several inflammatory cytokines, such as interleukin (IL)-6, tumor necrosis factor (TNF)-a, IL-1b, and IL-18, are increased in the cerebrospinal fluid (CSF) of patients affected by bacterial meningitis (Geldhoff et al, 2013; Chong et al, 2018). IL-1b and IL-18 are the main downstream effectors of inflammasome activation (Schroder and Tschopp, 2010; Gong et al, 2018), and may be involved in the neuroinflammatory response to bacterial meningitis
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