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MBL2 deficiency is associated with higher genomic bacterial loads during meningococcemia in young children

MBL2 deficiency is associated with higher genomic bacterial loads during meningococcemia in young children
MBL2 deficiency is associated with higher genomic bacterial loads during meningococcemia in young children

Mannose binding lectin (MBL2) is a soluble pattern recognition receptor that is key to generating innate immune responses to invasive infection, including against the cardinal Gram-negative bacterium Neisseria meningitidis. Individuals homozygous or heterozygous for any of three variant alleles of MBL2 (O/O or A/O genotypes) have deficient concentrations of MBL2 in circulating blood, but previous studies linking MBL deficiency to susceptibility to meningococcal disease have not revealed a consistent association. We genotyped 741 patients with microbiologically-proven meningococcal disease and correlated MBL2 genotype with plasma bacterial load of N. meningitidis with blood samples taken during hospital admission. We show that individuals with genotypes compatible with MBL2 deficiency have higher measurable levels of bacterial plasma genomic load with the greatest effect seen in children <2 years of age. However, the overall impact of this is minor, because there was no evidence that such genotypes are more common in children with meningococcal disease compared with uninfected cohorts. The findings suggest that MBL2 supports innate immune defence against meningococcal disease in the early months of life, before acquired immunity is sufficiently robust for effective natural protection.

Adolescent, Bacteremia, Bacterial Load, Blood, Child, Child, Preschool, Cohort Studies, Disease Susceptibility, Female, Genotype, Genotyping Techniques, Humans, Infant, Male, Mannose-Binding Lectin, Meningococcal Infections, Metabolism, Inborn Errors, Neisseria meningitidis, Journal Article, Research Support, Non-U.S. Gov't
1198-743X
1337-1342
Darton, T.C.
50865f34-d451-4d72-9173-607ad864fa02
Jack, D.L.
91f0e626-c2f4-4de2-bfbe-afd2e9284578
Johnson, M.
c3dc97e7-d850-45e0-9345-7727da368cfa
Borrow, R.
ae200ab8-f9f3-49c6-a161-c8fc31d00a58
Guiver, M.
a4a2ae54-a47b-48b4-86ff-7ffa374a8013
Kaczmarski, E.B.
b64d93b8-aaee-44f6-a7a3-715f8971d3b3
Turner, M.W.
8a3aa06d-eded-4906-a117-0f6e4887455a
Klein, N.J.
f01b50e5-cb25-4558-99aa-b697d534fb55
Read, R.C.
b5caca7b-0063-438a-b703-7ecbb6fc2b51
Darton, T.C.
50865f34-d451-4d72-9173-607ad864fa02
Jack, D.L.
91f0e626-c2f4-4de2-bfbe-afd2e9284578
Johnson, M.
c3dc97e7-d850-45e0-9345-7727da368cfa
Borrow, R.
ae200ab8-f9f3-49c6-a161-c8fc31d00a58
Guiver, M.
a4a2ae54-a47b-48b4-86ff-7ffa374a8013
Kaczmarski, E.B.
b64d93b8-aaee-44f6-a7a3-715f8971d3b3
Turner, M.W.
8a3aa06d-eded-4906-a117-0f6e4887455a
Klein, N.J.
f01b50e5-cb25-4558-99aa-b697d534fb55
Read, R.C.
b5caca7b-0063-438a-b703-7ecbb6fc2b51

Darton, T.C., Jack, D.L., Johnson, M., Borrow, R., Guiver, M., Kaczmarski, E.B., Turner, M.W., Klein, N.J. and Read, R.C. (2015) MBL2 deficiency is associated with higher genomic bacterial loads during meningococcemia in young children. Clinical Microbiology and Infection, 20 (12), 1337-1342. (doi:10.1111/1469-0691.12745).

Record type: Article

Abstract

Mannose binding lectin (MBL2) is a soluble pattern recognition receptor that is key to generating innate immune responses to invasive infection, including against the cardinal Gram-negative bacterium Neisseria meningitidis. Individuals homozygous or heterozygous for any of three variant alleles of MBL2 (O/O or A/O genotypes) have deficient concentrations of MBL2 in circulating blood, but previous studies linking MBL deficiency to susceptibility to meningococcal disease have not revealed a consistent association. We genotyped 741 patients with microbiologically-proven meningococcal disease and correlated MBL2 genotype with plasma bacterial load of N. meningitidis with blood samples taken during hospital admission. We show that individuals with genotypes compatible with MBL2 deficiency have higher measurable levels of bacterial plasma genomic load with the greatest effect seen in children <2 years of age. However, the overall impact of this is minor, because there was no evidence that such genotypes are more common in children with meningococcal disease compared with uninfected cohorts. The findings suggest that MBL2 supports innate immune defence against meningococcal disease in the early months of life, before acquired immunity is sufficiently robust for effective natural protection.

Full text not available from this repository.

More information

Accepted/In Press date: 26 June 2014
e-pub ahead of print date: 8 January 2015
Additional Information: © 2014 The Authors Clinical Microbiology and Infection © 2014 European Society of Clinical Microbiology and Infectious Diseases.
Keywords: Adolescent, Bacteremia, Bacterial Load, Blood, Child, Child, Preschool, Cohort Studies, Disease Susceptibility, Female, Genotype, Genotyping Techniques, Humans, Infant, Male, Mannose-Binding Lectin, Meningococcal Infections, Metabolism, Inborn Errors, Neisseria meningitidis, Journal Article, Research Support, Non-U.S. Gov't

Identifiers

Local EPrints ID: 416206
URI: https://eprints.soton.ac.uk/id/eprint/416206
ISSN: 1198-743X
PURE UUID: 8f936bf0-6441-458e-a6d4-cc8c2877f521
ORCID for R.C. Read: ORCID iD orcid.org/0000-0002-4297-6728

Catalogue record

Date deposited: 07 Dec 2017 17:30
Last modified: 14 Mar 2019 01:36

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