title: Strains Responsible for Invasive Meningococcal Disease in Patients With Terminal Complement Pathway Deficiencies.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  Unusual meningococcal strains with low level of virulence similar to carriage strains are most frequently responsible for IMD in patients with TPD.
authors.affiliation: Laboratory of Immunology, Hôpital européen Georges-Pompidou, Assistance Publique-Hôpitaux de Paris (AP-HP).|Institut Pasteur, Invasive Bacterial Infection and National Reference Center for Meningococci.|Paris Descartes University, Sorbonne Paris Cité.
authors.forename: Jérémie
authors.initials: J
authors.lastname: Rosain
authors.affiliation: Institut Pasteur, Invasive Bacterial Infection and National Reference Center for Meningococci.
authors.forename: Eva
authors.initials: E
authors.lastname: Hong
authors.affiliation: Department of Clinical Immunology, Hôpital Saint-Louis, AP-HP.|Institut National de la Santé et de la Recherche Médicale U1126, Hayem Center, Hôpital Saint-Louis, and.
authors.forename: Claire
authors.initials: C
authors.lastname: Fieschi
authors.affiliation: Laboratory of Immunology, Hôpital européen Georges-Pompidou, Assistance Publique-Hôpitaux de Paris (AP-HP).
authors.forename: Paula Vieira
authors.initials: PV
authors.lastname: Martins
authors.affiliation: Laboratory of Immunology, Hôpital européen Georges-Pompidou, Assistance Publique-Hôpitaux de Paris (AP-HP).
authors.forename: Carine
authors.initials: C
authors.lastname: El Sissy
authors.affiliation: Institut Pasteur, Invasive Bacterial Infection and National Reference Center for Meningococci.
authors.forename: Ala-Eddine
authors.initials: AE
authors.lastname: Deghmane
authors.affiliation: Immuno-Hematology Unit, Hôpital Robert Debré, AP-HP, Paris.
authors.forename: Marie
authors.initials: M
authors.lastname: Ouachée
authors.affiliation: Pediatric Hematology-Oncology Unit, Hôpital Mère Enfant, Hôpital de Nantes.
authors.forename: Caroline
authors.initials: C
authors.lastname: Thomas
authors.affiliation: University of Lille, U995-LIRIC, Lille Inflammation Research International Center.|Institut National de la Santé et de la Recherche Médicale, U995.|Departement of Internal Medicine and Clinical Immunology, Hôpital de Lille, and.|Centre National de Référence des Maladies Autoimmunes et Systémiques Rares (Sclérodermie), Lille.
authors.forename: David
authors.initials: D
authors.lastname: Launay
authors.affiliation: Pediatric Department, Hôpitaux universitaires Paris Seine Saint Denis, AP-HP, Paris 13 University.
authors.forename: Loïc
authors.initials: L
authors.lastname: de Pontual
authors.affiliation: Hematology Departement, Hôpital Necker-Enfants malades, AP-HP.|Institut National de la Santé et de la Recherche Médicale UMR1163, Imagine Institute, Paris Descartes University.
authors.forename: Felipe
authors.initials: F
authors.lastname: Suarez
authors.affiliation: Institut National de la Santé et de la Recherche Médicale UMR1163, Imagine Institute, Paris Descartes University.|Department of Pediatric Immunology, Hematology, and Rheumatology and.
authors.forename: Despina
authors.initials: D
authors.lastname: Moshous
authors.affiliation: Institut National de la Santé et de la Recherche Médicale UMR1163, Imagine Institute, Paris Descartes University.|Department of Pediatric Immunology, Hematology, and Rheumatology and.|Study Center for Primary Immunodeficiencies, Hôpital Necker-Enfants malades, AP-HP, and.
authors.forename: Capucine
authors.initials: C
authors.lastname: Picard
authors.affiliation: Institut Pasteur, Invasive Bacterial Infection and National Reference Center for Meningococci.
authors.forename: Muhamed-Kheir
authors.initials: MK
authors.lastname: Taha
authors.affiliation: Laboratory of Immunology, Hôpital européen Georges-Pompidou, Assistance Publique-Hôpitaux de Paris (AP-HP).|Institut National de la Santé et de la Recherche Médicale UMRS 1138, Cordeliers Research Center, Paris, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Frémeaux-Bacchi
mesh_terms: D000293:Adolescent; D002648:Child; D003167:Complement Activation; D015938:Complement Membrane Attack Complex / Q000172:deficiency* / Q000276:immunology; D005260:Female; D005820:Genetic Testing; D006801:Humans; D008297:Male; D008589:Meningococcal Infections / Q000276:immunology / Q000382:microbiology*; D009345:Neisseria meningitidis / Q000235:genetics* / Q000302:isolation & purification; D010297:Paris; D012189:Retrospective Studies; D014774:Virulence
chemical_list: D015938:Complement Membrane Attack Complex
keywords: Neisseria meningitidis; complement; membrane attack complex.; primary immunodeficiency; terminal complement pathway