Dataset Information

Individual responsiveness of macrophage migration inhibitory factor predicts long-term cognitive impairment after bacterial meningitis.

ABSTRACT:

Background

Patients with pneumococcal meningitis are at risk for death and neurological sequelae including cognitive impairment. Functional genetic polymorphisms of macrophage migration inhibitory factor (MIF) alleles have shown to predict mortality of pneumococcal meningitis.

Methods

We investigated whether MIF concentrations during the acute phase of disease were predictive for death in a nationwide prospective cohort study. Subsequently, we studied whether individual ex vivo MIF response years after meningitis was associated with the development of cognitive impairment.

Results

We found that in the acute illness of pneumococcal meningitis, higher plasma MIF concentrations were predictive for mortality (p?=?0.009). Cognitive impairment, examined 1-5 years after meningitis, was present in 11 of 79 patients after pneumococcal meningitis (14%), as compared to 1 of 63 (2%) in controls, and was consistently associated with individual variability in MIF production by peripheral blood mononuclear cells after ex vivo stimulation with various infectious stimuli.

Conclusions

Our study confirms the role of MIF in poor disease outcome of pneumococcal meningitis. Inter-individual differences in MIF production were associated with long-term cognitive impairment years after pneumococcal meningitis. The present study provides evidence that MIF mediates long-term cognitive impairment in bacterial meningitis survivors and suggests a potential role for MIF as a target of immune-modulating adjunctive therapy.

SUBMITTER: Kloek AT

PROVIDER: S-EPMC7789269 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Publications

Individual responsiveness of macrophage migration inhibitory factor predicts long-term cognitive impairment after bacterial meningitis.

Kloek Anne T AT Seron Mercedes Valls MV Schmand Ben B Tanck Michael W T MWT van der Ende Arie A Brouwer Matthijs C MC van de Beek Diederik D

Acta neuropathologica communications 20210106 1

<h4>Background</h4>Patients with pneumococcal meningitis are at risk for death and neurological sequelae including cognitive impairment. Functional genetic polymorphisms of macrophage migration inhibitory factor (MIF) alleles have shown to predict mortality of pneumococcal meningitis.<h4>Methods</h4>We investigated whether MIF concentrations during the acute phase of disease were predictive for death in a nationwide prospective cohort study. Subsequently, we studied whether individual ex vivo MI ...[more]

PMID: 33407905

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Project description:Background & aimsMacrophage migration inhibitory factor (MIF) is an inflammatory cytokine and an important regulator of innate immune responses. We hypothesised that serum concentrations of MIF are associated with disease severity and outcome in patients with decompensated cirrhosis and acute-on-chronic liver failure (ACLF).MethodsCirculating concentrations of MIF and its soluble receptor CD74 (sCD74) were determined in sera from 292 patients with acute decompensation of cirrhosis defined as new onset or worsening of ascites requiring hospitalisation. Of those, 78 (27%) had ACLF. Short-term mortality was assessed 90 days after inclusion.ResultsAlthough serum concentrations of MIF and sCD74 did not correlate with liver function parameters or ACLF, higher MIF (optimum cut-off >2.3 ng/ml) and lower concentrations of sCD74 (optimum cut-off <66.5 ng/ml) both indicated poorer 90-day transplant-free survival in univariate analyses (unadjusted hazard ratio [HR] 2.01 [1.26-3.22]; p = 0.004 for MIF; HR 0.59 [0.38-0.92]; p = 0.02 for sCD74) and after adjustment in multivariable models. Higher MIF concentrations correlated with surrogates of systemic inflammation (white blood cells, p = 0.005; C-reactive protein, p = 0.05) and were independent of genetic MIF promoter polymorphisms. Assessment of MIF plasma concentrations in portal venous blood and matched blood samples from the right atrium in a second cohort of patients undergoing transjugular intrahepatic portosystemic shunt insertion revealed a transhepatic MIF gradient with higher concentrations in the right atrial blood.ConclusionsSerum concentrations of MIF and its soluble receptor CD74 predict 90-day transplant-free survival in patients with acute decompensation of cirrhosis. This effect was independent of liver function and genetic predispositions, but rather reflected systemic inflammation. Therefore, MIF and sCD74 represent promising prognostic markers beyond classical scoring systems in patients at risk of ACLF.Lay summaryInflammatory processes contribute to the increased risk of death in patients with cirrhosis and ascites. We show that patients with high serum levels of the inflammatory cytokine macrophage migration inhibitory factor (MIF) alongside low levels of its binding receptor sCD74 in blood indicate an increased mortality risk in patients with ascites. The cirrhotic liver is a relevant source of elevated circulating MIF levels.

Project description:BackgroundMild cognitive impairment (MCI) may occur due to several forms of neurodegenerative diseases and non-degenerative conditions and is associated with cognitive impairment that does not affect everyday activities. For a timely diagnosis of MCI to prevent progression to dementia, a screening tool of fast, low-cost and easy access is needed. Recent research on eye movement hints it a potential application for the MCI screening. However, the precise extent of cognitive function decline and eye-movement control alterations in patients with MCI is still unclear.ObjectiveThis study examined executive control deficits and saccade behavioral changes in patients with MCI using comprehensive neuropsychological assessment and interleaved saccade paradigms.MethodsPatients with MCI (n = 79) and age-matched cognitively healthy controls (HC) (n = 170) completed four saccadic eye-movement paradigms: prosaccade (PS)/antisaccade (AS), Go/No-go, and a battery of neuropsychological tests.ResultsThe findings revealed significantly longer latency in patients with MCI than in HC during the PS task. Additionally, patients with MCI had a lower proportion of correct responses and a marked increase in inhibition errors for both PS/AS and Go/No-go tasks. Furthermore, when patients with MCI made errors, they failed to self-correct many of these inhibition errors. In addition to the increase in inhibition errors and uncorrected inhibition errors, patients with MCI demonstrated a trend toward increased correction latencies. We also showed a relationship between neuropsychological scores and correct and error saccade responses.ConclusionOur results demonstrate that, similar to patients with Alzheimer's dementia (AD), patients with MCI generate a high proportion of erroneous saccades toward the prepotent target and fail to self-correct many of these errors, which is consistent with an impairment of inhibitory control and error monitoring.SignificanceThe interleaved PS/AS and Go/No-go paradigms are sensitive and objective at detecting subtle cognitive deficits and saccade changes in MCI, indicating that these saccadic eye movement paradigms have clinical potential as a screening tool for MCI.

Dataset Information

Individual responsiveness of macrophage migration inhibitory factor predicts long-term cognitive impairment after bacterial meningitis.

Background

Methods

Results

Conclusions

Publications

Individual responsiveness of macrophage migration inhibitory factor predicts long-term cognitive impairment after bacterial meningitis.

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