A functional microsatellite of the macrophage migration inhibitory factor gene associated with meningococcal disease

Macrophage migration inhibitory factor (MIF) is an abundantly expressed proinflammatory cytokine playing a critical role in innate immunity and sepsis and other inflammatory diseases. We examined whether functional MIF gene polymorphisms (-794 CATT5-8 microsatellite and -173 G/C SNP) were associated with the occurrence and outcome of meningococcal disease in children. The CATT5 allele was associated with the probability of death predicted by the Pediatric Index of Mortality 2 (P = 0.001), which increased in correlation with the CATT5 copy number (P = 0.04). The CATT5 allele, but not the -173 G/C alleles, was also associated with the actual mortality from meningoccal sepsis [OR 2.72 (1.2-6.4), P = 0.02]. A family-based association test (i.e., transmission disequilibrium test) performed in 240 trios with 1 afflicted offspring indicated that CATT5 was a protective allele (P = 0.02) for the occurrence of meningococcal disease. At baseline and after stimulation with Neisseria meningitidis in THP-1 monocytic cells or in a whole-blood assay, CATT5 was found to be a low-expression MIF allele (P = 0.005 and P = 0.04 for transcriptional activity; P = 0.09 and P = 0.09 for MIF production). Taken together, these data suggest that polymorphisms of the MIF gene affecting MIF expression are associated with the occurrence, severity, and outcome of meningococcal disease in children.-Renner, P., Roger, T., Bochud, P.-Y., Sprong, T., Sweep, F. C. G. J., Bochud, M., Faust, S. N., Haralambous, E., Betts, H., Chanson, A.-L., Reymond, M. K., Mermel, E., Erard, V., van Deuren, M., Read, R. C., Levin, M., Calandra, T. A functional microsatellite of the macrophage migration inhibitory factor gene associated with meningococcal disease. FASEB J. 26, 907-916 (2012). www.fasebj.org