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National Academy of Sciences, Proceedings of the National Academy of Sciences, 13(113), p. 3597-3602, 2016

DOI: 10.1073/pnas.1520727113

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Functional polymorphisms of macrophage migration inhibitory factor as predictors of morbidity and mortality of pneumococcal meningitis

Journal article published in 2016 by Athina Savva, Matthijs C. Brouwer, Thierry Roger ORCID, Mercedes Valls Serón, Didier Le Roy, Didier Le Roy, Bart Ferwerda ORCID, Arie van der Ende, Pierre-Yves Bochud, Diederik van de Beek ORCID, Thierry Calandra ORCID
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

Significance Pneumococcal meningitis, the most frequent cause of bacterial meningitis in adults, is associated with substantial morbidity and mortality. In a prospective, nationwide cohort of patients with pneumococcal meningitis, macrophage migration inhibitory factor (MIF), a proinflammatory mediator, was identified as a previously unidentified genetic marker of patient’s outcome. High-expression MIF alleles were associated with disease severity and death, a finding consistent with the harmful consequences of robust proinflammatory cytokine responses on brain edema and neuronal damage in the course of bacterial meningitis. These results provide strong evidence that functional MIF polymorphisms are genetic predictors of morbidity and mortality of pneumococcal meningitis and suggest that MIF is a potential target for immune-modulating adjunctive therapies.