title: Spectrum and management of complement immunodeficiencies (excluding hereditary angioedema) across Europe.
abstract: BACKGROUND
  Complement immunodeficiencies (excluding hereditary angioedema and mannose binding lectin deficiency) are rare. Published literature consists largely of case reports and small series. We collated data from 18 cities across Europe to provide an overview of primarily homozygous, rather than partial genotypes and their impact and management.
  
  
  METHODS
  Patients were recruited through the ESID registry. Clinical and laboratory information was collected onto standardized forms and analyzed using SPSS software.
  
  
  RESULTS
  Seventy-seven patients aged 1 to 68 years were identified. 44 % presented in their first decade of life. 29 % had C2 deficiency, defects in 11 other complement factors were found. 50 (65 %) had serious invasive infections. 61 % of Neisseria meningitidis infections occurred in patients with terminal pathway defects, while 74 % of Streptococcus pneumoniae infections occurred in patients with classical pathway defects (p < 0.001). Physicians in the UK were more likely to prescribe antibiotic prophylaxis than colleagues on the Continent for patients with classical pathway defects. After diagnosis, 16 % of patients suffered serious bacterial infections. Age of the patient and use of prophylactic antibiotics were not associated with subsequent infection risk. Inflammatory/autoimmune diseases were not seen in patients with terminal pathway, but in one third of patients classical and alternative pathway defects.
  
  
  CONCLUSIONS
  The clinical phenotypes of specific complement immunodeficiencies vary considerably both in terms of the predominant bacterial pathogen, and the risk and type of auto-inflammatory disease. Appreciation of these phenotypic differences should help both immunologists and other specialists in their diagnosis and management of these rare and complex patients.
authors: Paediatric Immunology, University of Manchester, Manchester, UK.
authors: A J
authors: AJ
authors: Turley
authors: B
authors: B
authors: Gathmann
authors: C
authors: C
authors: Bangs
authors: M
authors: M
authors: Bradbury
authors: S
authors: S
authors: Seneviratne
authors: L I
authors: LI
authors: Gonzalez-Granado
authors: S
authors: S
authors: Hackett
authors: N
authors: N
authors: Kutukculer
authors: H
authors: H
authors: Alachkar
authors: S
authors: S
authors: Hambleton
authors: H
authors: H
authors: Ritterbusch
authors: P
authors: P
authors: Kralickova
authors: L
authors: L
authors: Marodi
authors: M G
authors: MG
authors: Seidel
authors: G
authors: G
authors: Dueckers
authors: J
authors: J
authors: Roesler
authors: A
authors: A
authors: Huissoon
authors: H
authors: H
authors: Baxendale
authors: J
authors: J
authors: Litzman
authors: P D
authors: PD
authors: Arkwright
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D003167:Complement Activation / Q000235:genetics / Q000276:immunology; D003165:Complement System Proteins / Q000172:deficiency* / Q000235:genetics* / Q000276:immunology; D003241:Consanguinity; D016208:Databases, Factual; D019468:Disease Management; D005060:Europe / Q000453:epidemiology; D005260:Female; D005838:Genotype; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics* / Q000628:therapy; D007223:Infant; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D003165:Complement System Proteins