Strains Responsible for Invasive Meningococcal Disease in Patients With Terminal Complement Pathway Deficiencies

J Infect Dis. 2017 Apr 15;215(8):1331-1338. doi: 10.1093/infdis/jix143.

Abstract

Background: Patients with terminal complement pathway deficiency (TPD) are susceptible to recurrent invasive meningococcal disease (IMD). Neisseria meningitidis (Nm) strains infecting these patients are poorly documented in the literature.

Methods: We identified patients with TPD and available Nm strains isolated during IMD. We investigated the genetic basis of the different TPDs and the characteristics of the Nm strains.

Results: We included 56 patients with C5 (n = 8), C6 (n = 20), C7 (n = 18), C8 (n = 9), or C9 (n = 1) deficiency. Genetic study was performed in 47 patients and 30 pathogenic variants were identified in the genes coding for C5 (n = 4), C6 (n = 5), C7 (n = 12), C8 (n = 7), and C9 (n = 2). We characterized 61 Nm strains responsible for IMD in the 56 patients with TPD. The most frequent strains belonged to groups Y (n = 27 [44%]), B (n = 18 [30%]), and W (n = 8 [13%]). Hyperinvasive clonal complexes (CC11, CC32, CC41/44, and CC269) were responsible for 21% of IMD cases. The CC23 predominates and represented 26% of all invasive isolates. Eleven of the 15 clonal complexes identified fit to 12 different clonal complexes belonging to carriage strains.

Conclusions: Unusual meningococcal strains with low level of virulence similar to carriage strains are most frequently responsible for IMD in patients with TPD.

Keywords: Neisseria meningitidis; complement; membrane attack complex.; primary immunodeficiency; terminal complement pathway.

MeSH terms

  • Adolescent
  • Child
  • Complement Activation*
  • Complement Membrane Attack Complex / deficiency*
  • Complement Membrane Attack Complex / immunology
  • Female
  • Genetic Testing
  • Humans
  • Male
  • Meningococcal Infections / immunology
  • Meningococcal Infections / microbiology*
  • Neisseria meningitidis / genetics*
  • Neisseria meningitidis / isolation & purification
  • Paris
  • Retrospective Studies
  • Virulence

Substances

  • Complement Membrane Attack Complex