Genetic variation in inflammasome genes is associated with outcome in bacterial meningitis.
Bacterial meningitis is a severe and deadly disease, most commonly caused by Streptococcus pneumoniae. Disease outcome has been related to severity of the inflammatory response in the subarachnoid space. Inflammasomes are intracellular signaling complexes contributing to this inflammatory response. The role of genetic variation in inflammasome genes in bacterial meningitis is largely unknown. In a prospective nationwide cohort of patients with pneumococcal meningitis, we performed a genetic association study and found that single-nucleotide polymorphisms in the inflammasome genes CARD8 (rs2043211) and NLRP1 (rs11621270) are associated with poor disease outcome. Levels of the inflammasome associated cytokines interleukin (IL)-1β and IL-18 in cerebrospinal fluid also correlated with clinical outcome, but were not associated with the CARD8 and NLRP1 polymorphisms. Our results implicate an important role of genetic variation in inflammasome genes in the regulation of inflammatory response and clinical outcome in patients with bacterial meningitis.
Department of Neurology H2, Center of Infection and Immunity Amsterdam-CINIMA, Academic Medical Center, University of Amsterdam, P.O. Box 22660, 1100 DD Amsterdam, The Netherlands.
Madelijn
M
Geldhoff
Barry B
BB
Mook-Kanamori
Matthijs C
MC
Brouwer
Mercedes
M
Valls Seron
Frank
F
Baas
Arie
A
van der Ende
Diederik
D
van de Beek
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D053468:CARD Signaling Adaptor Proteins / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D058847:Inflammasomes / Q000235:genetics*; D020382:Interleukin-18 / Q000134:cerebrospinal fluid; D053583:Interleukin-1beta / Q000134:cerebrospinal fluid; D008297:Male; D008586:Meningitis, Pneumococcal / Q000235:genetics* / Q000401:mortality*; D008875:Middle Aged; D000070576:NLR Proteins; D009363:Neoplasm Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D011446:Prospective Studies
D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D053468:CARD Signaling Adaptor Proteins; C455623:CARD8 protein, human; D058847:Inflammasomes; D020382:Interleukin-18; D053583:Interleukin-1beta; D000070576:NLR Proteins; C427903:NLRP1 protein, human; D009363:Neoplasm Proteins